TY - Generic T1 - Draft Genome Sequences from a Novel Clade of Bacillus cereus sensu lato Strains Isolated from the International Space Station Y1 - 2017 A1 - Kasthuri Venkateswaran A1 - Aleksandra Checinska-Sielaff A1 - Joy Klubnik A1 - Todd Treangen A1 - M.J. Rosovitz A1 - Nicholas H. Bergman JA - Genome Announcements VL - 1 ER - TY - JOUR T1 - Sequestration of nematocysts by divergent cnidarian predators: mechanism, function, and evolution JF - Invertebrate Biology Y1 - 2017 A1 - Goodheart, Jessica A1 - Bely, Alexandra E. VL - 136 UR - http://doi.wiley.com/10.1111/ivb.2017.136.issue-1http://doi.wiley.com/10.1111/ivb.12154http://onlinelibrary.wiley.com/wol1/doi/10.1111/ivb.12154/fullpdfhttps://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Fivb.12154 CP - 1 J1 - Invertebr Biol M3 - 10.1111/ivb.2017.136.issue-110.1111/ivb.12154 ER - TY - BOOK T1 - Better Identification of Repeats in Metagenomic Scaffolding Y1 - 2016 A1 - Ghurye, Jay A1 - Pop, Mihai PB - Springer International Publishing CY - Cham VL - 9838 SN - 978-3-319-43680-7 UR - http://link.springer.com/10.1007/978-3-319-43681-4http://link.springer.com/content/pdf/10.1007/978-3-319-43681-4 M3 - 10.1007/978-3-319-43681-410.1007/978-3-319-43681-4_14 ER - TY - JOUR T1 - Capturing the most wanted taxa through cross-sample correlations JF - The ISME Journal Y1 - 2016 A1 - Almeida, Mathieu A1 - Pop, Mihai A1 - Le Chatelier, Emmanuelle A1 - Prifti, Edi A1 - Pons, Nicolas A1 - Ghozlane, Amine A1 - Ehrlich, S Dusko UR - http://www.nature.com/doifinder/10.1038/ismej.2016.35 J1 - ISME J M3 - 10.1038/ismej.2016.35 ER - TY - JOUR T1 - Data-Driven Metabolic Pathway Compositions Enhance Cancer Survival Prediction JF - PLOS Computational Biology Y1 - 2016 A1 - Auslander, Noam A1 - Wagner, Allon A1 - Oberhardt, Matthew A1 - Ruppin, Eytan ED - Przytycka, Teresa M. VL - 12 UR - http://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1005125 CP - 9 J1 - PLoS Comput Biol M3 - 10.1371/journal.pcbi.1005125 ER - TY - JOUR T1 - Distinct genomic and epigenomic features demarcate hypomethylated blocks in colon cancer JF - BMC Cancer Y1 - 2016 A1 - Sharmin, Mahfuza A1 - Bravo, éctor Corrada A1 - Hannenhalli, Sridhar VL - 16447943582141728452710921541113181321912 UR - http://www.biomedcentral.com/1471-2407/16/88http://link.springer.com/content/pdf/10.1186/s12885-016-2128-1 CP - 17143623521101753416231113 J1 - BMC Cancer M3 - 10.1186/s12885-016-2128-1 ER - TY - JOUR T1 - Diversity in a Polymicrobial Community Revealed by Analysis of Viromes, Endolysins and CRISPR Spacers. JF - PLoS One Y1 - 2016 A1 - Davison, Michelle A1 - Todd Treangen A1 - Koren, Sergey A1 - Pop, Mihai A1 - Bhaya, Devaki AB -

The polymicrobial biofilm communities in Mushroom and Octopus Spring in Yellowstone National Park (YNP) are well characterized, yet little is known about the phage populations. Dominant species, Synechococcus sp. JA-2-3B'a(2-13), Synechococcus sp. JA-3-3Ab, Chloroflexus sp. Y-400-fl, and Roseiflexus sp. RS-1, contain multiple CRISPR-Cas arrays, suggesting complex interactions with phage predators. To analyze phage populations from Octopus Spring biofilms, we sequenced a viral enriched fraction. To assemble and analyze phage metagenomic data, we developed a custom module, VIRITAS, implemented within the MetAMOS framework. This module bins contigs into groups based on tetranucleotide frequencies and CRISPR spacer-protospacer matching and ORF calling. Using this pipeline we were able to assemble phage sequences into contigs and bin them into three clusters that corroborated with their potential host range. The virome contained 52,348 predicted ORFs; some were clearly phage-like; 9319 ORFs had a recognizable Pfam domain while the rest were hypothetical. Of the recognized domains with CRISPR spacer matches, was the phage endolysin used by lytic phage to disrupt cells. Analysis of the endolysins present in the thermophilic cyanophage contigs revealed a subset of characterized endolysins as well as a Glyco_hydro_108 (PF05838) domain not previously associated with sequenced cyanophages. A search for CRISPR spacer matches to all identified phage endolysins demonstrated that a majority of endolysin domains were targets. This strategy provides a general way to link host and phage as endolysins are known to be widely distributed in bacteriophage. Endolysins can also provide information about host cell wall composition and have the additional potential to be used as targets for novel therapeutics.

VL - 11 CP - 9 M3 - 10.1371/journal.pone.0160574 ER - TY - JOUR T1 - Dual Transcriptome Profiling of Leishmania-Infected Human Macrophages Reveals Distinct Reprogramming Signatures JF - mBio Y1 - 2016 A1 - Fernandes, Maria Cecilia A1 - Dillon, Laura A. L. A1 - Belew, Ashton Trey A1 - Bravo, Héctor Corrada A1 - Mosser, David M. A1 - El-Sayed, Najib M. VL - 7 UR - http://mbio.asm.org/lookup/doi/10.1128/mBio.00027-16https://syndication.highwire.org/content/doi/10.1128/mBio.00027-16 CP - 3 J1 - mBio M3 - 10.1128/mBio.00027-16 ER - TY - JOUR T1 - The fruRBA operon is necessary for Group A Streptococcal growth in fructose and for resistance to neutrophil killing during growth in whole human blood. JF - Infect Immun Y1 - 2016 A1 - Valdes, Kayla M A1 - Sundar, Ganesh S A1 - Vega, Luis A A1 - Belew, Ashton T A1 - Islam, Emrul A1 - Binet, Rachel A1 - El-Sayed, Najib M A1 - Le Breton, Yoann A1 - McIver, Kevin S AB -

Bacterial pathogens rely on the availability of nutrients for survival in the host environment. The phosphoenolpyruvate-phosphotransferase system (PTS) is a global regulatory network connecting sugar uptake with signal transduction. Since the fructose PTS has been shown to impact virulence in several Streptococci, including the human pathogen S. pyogenes (the group A Streptococcus, GAS), we characterized its role in carbon metabolism and pathogenesis in the M1T1 strain 5448. Growth in fructose as a sole carbon source resulted in 103 genes affected transcriptionally, where the fru locus (fruRBA) was the most induced. RT-PCR showed that fruRBA formed an operon, which was repressed by FruR in the absence of fructose, in addition to being under carbon catabolic repression. Growth assays and carbon utilization profiles revealed that although the entire fru operon was required for growth in fructose, FruA was the main transporter for fructose and was also involved in the utilization of three additional PTS sugars: cellobiose, mannitol, and N-acetyl-D-galactosamine. Inactivation of sloR, a fruA homolog that was also up regulated in presence of fructose, failed to reveal a role as a secondary fructose transporter. Whereas the ability of both ΔfruR and ΔfruB mutants to survive in the presence of whole human blood or neutrophils was impaired, the phenotype was not reproduced in murine whole blood, nor were those mutants attenuated in a mouse intraperitoneal infection. Since the ΔfruA mutant exhibited no phenotype in the human or mouse assays, we propose that FruR and FruB are important for GAS survival in a human-specific environment.

M3 - 10.1128/IAI.01296-15 ER - TY - JOUR T1 - Functional Alignment of Metabolic Networks. JF - J Comput Biol Y1 - 2016 A1 - Mazza, Arnon A1 - Wagner, Allon A1 - Ruppin, Eytan A1 - Sharan, Roded AB -

Network alignment has become a standard tool in comparative biology, allowing the inference of protein function, interaction, and orthology. However, current alignment techniques are based on topological properties of networks and do not take into account their functional implications. Here we propose, for the first time, an algorithm to align two metabolic networks by taking advantage of their coupled metabolic models. These models allow us to assess the functional implications of genes or reactions, captured by the metabolic fluxes that are altered following their deletion from the network. Such implications may spread far beyond the region of the network where the gene or reaction lies. We apply our algorithm to align metabolic networks from various organisms, ranging from bacteria to humans, showing that our alignment can reveal functional orthology relations that are missed by conventional topological alignments.

M3 - 10.1089/cmb.2015.0203 ER - TY - JOUR T1 - Genome-scale study reveals reduced metabolic adaptability in patients with non-alcoholic fatty liver disease JF - Nature Communications Y1 - 2016 A1 - ötyläinen, Tuulia A1 - Jerby, Livnat A1 - äjä, Elina M. A1 - Mattila, Ismo A1 - äntti, Sirkku A1 - Auvinen, Petri A1 - Gastaldelli, Amalia A1 - ärvinen, Hannele A1 - Ruppin, Eytan A1 - šič, Matej VL - 7 UR - http://www.nature.com/doifinder/10.1038/ncomms9994 J1 - Nat Comms M3 - 10.1038/ncomms9994 ER - TY - JOUR T1 - Genome-scale study reveals reduced metabolic adaptability in patients with non-alcoholic fatty liver disease. JF - Nat Commun Y1 - 2016 A1 - Hyötyläinen, Tuulia A1 - Jerby, Livnat A1 - Petäjä, Elina M A1 - Mattila, Ismo A1 - Jäntti, Sirkku A1 - Auvinen, Petri A1 - Gastaldelli, Amalia A1 - Yki-Järvinen, Hannele A1 - Ruppin, Eytan A1 - Orešič, Matej AB -

Non-alcoholic fatty liver disease (NAFLD) is a major risk factor leading to chronic liver disease and type 2 diabetes. Here we chart liver metabolic activity and functionality in NAFLD by integrating global transcriptomic data, from human liver biopsies, and metabolic flux data, measured across the human splanchnic vascular bed, within a genome-scale model of human metabolism. We show that an increased amount of liver fat induces mitochondrial metabolism, lipolysis, glyceroneogenesis and a switch from lactate to glycerol as substrate for gluconeogenesis, indicating an intricate balance of exacerbated opposite metabolic processes in glycemic regulation. These changes were associated with reduced metabolic adaptability on a network level in the sense that liver fat accumulation puts increasing demands on the liver to adaptively regulate metabolic responses to maintain basic liver functions. We propose that failure to meet excessive metabolic challenges coupled with reduced metabolic adaptability may lead to a vicious pathogenic cycle leading to the co-morbidities of NAFLD.

VL - 7 M3 - 10.1038/ncomms9994 ER - TY - JOUR T1 - Heterogeneity of transcription factor binding specificity models within and across cell lines JF - Genome Research Y1 - 2016 A1 - Sharmin, Mahfuza A1 - Bravo, éctor Corrada A1 - Hannenhalli, Sridhar UR - http://genome.cshlp.org/lookup/doi/10.1101/gr.199166.115 J1 - Genome Res. M3 - 10.1101/gr.199166.115 ER - TY - JOUR T1 - Identification and genomic analysis of a novel group C orthobunyavirus isolated from a mosquito captured near Iquitos, Peru JF - PLoS Negl Trop Dis Y1 - 2016 A1 - Todd Treangen A1 - Schoeler, George A1 - Phillippy, Adam M A1 - Bergman, Nicholas H A1 - Turell, Michael J VL - 10 ER - TY - JOUR T1 - Identification guide to the heterobranch sea slugs (Mollusca: Gastropoda) from Bocas del Toro, Panama JF - Marine Biodiversity Records Y1 - 2016 A1 - Goodheart, Jessica A1 - Ellingson, Ryan A. A1 - Vital, Xochitl G. A1 - ão Filho, Hilton C. A1 - McCarthy, Jennifer B. A1 - Medrano, Sabrina M. A1 - Bhave, Vishal J. A1 - ía-Méndez, Kimberly A1 - énez, Lina M. A1 - ópez, Gina A1 - Hoover, Craig A. A1 - Awbrey, Jaymes D. A1 - De Jesus, Jessika M. A1 - Gowacki, William A1 - Krug, Patrick J. A1 - és, Ángel VL - 96737453830254034557880541418411912544728739317415779780725696418782226404216145163412560451520488424050829677 UR - http://mbr.biomedcentral.com/articles/10.1186/s41200-016-0048-zhttp://link.springer.com/content/pdf/10.1186/s41200-016-0048-z CP - 12343–4 J1 - Mar Biodivers Rec M3 - 10.1186/s41200-016-0048-z ER - TY - JOUR T1 - The fruRBA Operon Is Necessary for Group A Streptococcal Growth in Fructose and for Resistance to Neutrophil Killing during Growth in Whole Human Blood JF - Infection and Immunity Y1 - 2016 A1 - Valdes, Kayla M. A1 - Sundar, Ganesh S. A1 - Vega, Luis A. A1 - Belew, Ashton T. A1 - Islam, Emrul A1 - Binet, Rachel A1 - El-Sayed, Najib M. A1 - Le Breton, Yoann A1 - McIver, Kevin S. ED - Camilli, A. VL - 84 UR - http://iai.asm.org/lookup/doi/10.1128/IAI.01296-15 CP - 4 J1 - Infect. Immun. M3 - 10.1128/IAI.01296-15 ER - TY - JOUR T1 - Individual-specific changes in the human gut microbiota after challenge with enterotoxigenic Escherichia coli and subsequent ciprofloxacin treatment JF - BMC Genomics Y1 - 2016 A1 - Pop, Mihai A1 - Paulson, Joseph N. A1 - Chakraborty, Subhra A1 - Astrovskaya, Irina A1 - Lindsay, Brianna R. A1 - Li, Shan A1 - Bravo, éctor Corrada A1 - Harro, Clayton A1 - Parkhill, Julian A1 - Walker, Alan W. A1 - Walker, Richard I. A1 - Sack, David A. A1 - Stine, O. Colin VL - 17183412111831230710512122489914142853341501081566039108377115651846133171373920352123327102188151723 UR - http://bmcgenomics.biomedcentral.com/articles/10.1186/s12864-016-2777-0http://link.springer.com/content/pdf/10.1186/s12864-016-2777-0 CP - 1326124105778571763174155114260523Suppl 1611Suppl 26-7Suppl 197591Pt 11321131 Suppl241Database issue1612210375335 J1 - BMC Genomics M3 - 10.1186/s12864-016-2777-0 ER - TY - JOUR T1 - A joint analysis of transcriptomic and metabolomic data uncovers enhanced enzyme-metabolite coupling in breast cancer. JF - Sci Rep Y1 - 2016 A1 - Auslander, Noam A1 - Yizhak, Keren A1 - Weinstock, Adam A1 - Budhu, Anuradha A1 - Tang, Wei A1 - Wang, Xin Wei A1 - Ambs, Stefan A1 - Ruppin, Eytan AB -

Disrupted regulation of cellular processes is considered one of the hallmarks of cancer. We analyze metabolomic and transcriptomic profiles jointly collected from breast cancer and hepatocellular carcinoma patients to explore the associations between the expression of metabolic enzymes and the levels of the metabolites participating in the reactions they catalyze. Surprisingly, both breast cancer and hepatocellular tumors exhibit an increase in their gene-metabolites associations compared to noncancerous adjacent tissues. Following, we build predictors of metabolite levels from the expression of the enzyme genes catalyzing them. Applying these predictors to a large cohort of breast cancer samples we find that depleted levels of key cancer-related metabolites including glucose, glycine, serine and acetate are significantly associated with improved patient survival. Thus, we show that the levels of a wide range of metabolites in breast cancer can be successfully predicted from the transcriptome, going beyond the limited set of those measured.

VL - 6 M3 - 10.1038/srep29662 ER - TY - CONF T1 - Limitations of Current Approaches for Reference-Free, Graph-Based Variant Detection T2 - the 7th ACM International ConferenceProceedings of the 7th ACM International Conference on Bioinformatics, Computational Biology, and Health Informatics - BCB '16 Y1 - 2016 A1 - Bateman, Amelia A1 - Todd Treangen A1 - Pop, Mihai JA - the 7th ACM International ConferenceProceedings of the 7th ACM International Conference on Bioinformatics, Computational Biology, and Health Informatics - BCB '16 PB - ACM Press CY - Seattle, WA, USANew York, New York, USA SN - 9781450342254 UR - http://dl.acm.org/citation.cfm?doid=2975167http://dl.acm.org/citation.cfm?doid=2975167.2985653 M3 - 10.1145/297516710.1145/2975167.2985653 ER - TY - JOUR T1 - Longitudinal analysis of the lung microbiota of cynomolgous macaques during long-term SHIV infection JF - Microbiome Y1 - 2016 A1 - Morris, Alison A1 - Paulson, Joseph N. A1 - Talukder, Hisham A1 - Tipton, Laura A1 - Kling, Heather A1 - Cui, Lijia A1 - Fitch, Adam A1 - Pop, Mihai A1 - Norris, Karen A. A1 - Ghedin, Elodie VL - 4320384718719152130282021211818418719223326578105723 UR - http://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-016-0183-0http://link.springer.com/content/pdf/10.1186/s40168-016-0183-0 CP - 158836212108125732558101131110121arXiv:1006.3316 J1 - Microbiome M3 - 10.1186/s40168-016-0183-0 ER - TY - JOUR T1 - Maligner: a fast ordered restriction map aligner. JF - Bioinformatics Y1 - 2016 A1 - Mendelowitz, Lee M A1 - Schwartz, David C A1 - Pop, Mihai AB -

MOTIVATION: The Optical Mapping System discovers structural variants and potentiates sequence assembly of genomes via scaffolding and comparisons that globally validate or correct sequence assemblies. Despite its utility, there are few publicly available tools for aligning optical mapping datasets.

RESULTS: Here we present software, named 'Maligner', for the alignment of both single molecule restriction maps (Rmaps) and in silico restriction maps of sequence contigs to a reference. Maligner provides two modes of alignment: an efficient, sensitive dynamic programming implementation that scales to large eukaryotic genomes, and a faster indexed based implementation for finding alignments with unmatched sites in the reference but not the query. We compare our software to other publicly available tools on Rmap datasets and show that Maligner finds more correct alignments in comparable runtime. Lastly, we introduce the M-Score statistic for normalizing alignment scores across restriction maps and demonstrate its utility for selecting high quality alignments.

AVAILABILITY AND IMPLEMENTATION: The Maligner software is written in C ++ and is available at https://github.com/LeeMendelowitz/maligner under the GNU General Public License.

CONTACT: mpop@umiacs.umd.edu.

VL - 32 CP - 7 M3 - 10.1093/bioinformatics/btv711 ER - TY - JOUR T1 - Mash: fast genome and metagenome distance estimation using MinHash JF - Genome Biology Y1 - 2016 A1 - Ondov, Brian D. A1 - Todd Treangen A1 - Melsted, áll A1 - Mallonee, Adam B. A1 - Bergman, Nicholas H. A1 - Koren, Sergey A1 - Phillippy, Adam M. UR - http://genomebiology.biomedcentral.com/articles/10.1186/s13059-016-0997-xhttp://link.springer.com/content/pdf/10.1186/s13059-016-0997-x CP - 1Suppl 19 J1 - Genome Biol M3 - 10.1186/s13059-016-0997-x ER - TY - JOUR T1 - Metabolic Network Prediction of Drug Side Effects JF - Cell Systems Y1 - 2016 A1 - Shaked, Itay A1 - Oberhardt,  A. A1 - Atias, Nir A1 - Sharan, Roded A1 - Ruppin, Eytan VL - 2 UR - http://linkinghub.elsevier.com/retrieve/pii/S2405471216300734http://api.elsevier.com/content/article/PII:S2405471216300734?httpAccept=text/xmlhttp://api.elsevier.com/content/article/PII:S2405471216300734?httpAccept=text/plain CP - 3 J1 - Cell Systems M3 - 10.1016/j.cels.2016.03.001 ER - TY - JOUR T1 - Metagenomic Assembly: Overview, Challenges and Applications JF - Yale J Biol Med Y1 - 2016 A1 - Jay S. Ghurye A1 - Victoria Cepeda-Espinoza A1 - Mihai Pop VL - 89 UR - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5045144/ CP - 3 ER - TY - JOUR T1 - methylFlow: cell-specific methylation pattern reconstruction from high-throughput bisulfite-converted DNA sequencing JF - Bioinformatics Y1 - 2016 A1 - Dorri, Faezeh A1 - Mendelowitz, Lee A1 - Corrada Bravo, éctor VL - 32 UR - https://academic.oup.com/bioinformatics/article-lookup/doi/10.1093/bioinformatics/btw287https://academic.oup.com/bioinformatics/article/32/11/1618/1743421/methylFlow-cellspecific-methylation-pattern CP - 11 J1 - Bioinformatics M3 - 10.1093/bioinformatics/btw287 ER - TY - JOUR T1 - A pathway-centric view of spatial proximity in the 3D nucleome across cell lines JF - Scientific Reports Y1 - 2016 A1 - Karathia, Hiren A1 - Kingsford, Carl A1 - Girvan, Michelle A1 - Hannenhalli, Sridhar VL - 6 UR - http://www.nature.com/articles/srep39279 J1 - Sci. Rep. M3 - 10.1038/srep39279 ER - TY - JOUR T1 - A perspective on 16S rRNA operational taxonomic unit clustering using sequence similarity JF - npj Biofilms and Microbiomes Y1 - 2016 A1 - Nguyen, Nam-phuong A1 - Warnow, Tandy A1 - Pop, Mihai A1 - White, Bryan VL - 2 UR - http://www.nature.com/articles/npjbiofilms20164 J1 - npj Biofilms and Microbiomes M3 - 10.1038/npjbiofilms.2016.4 ER - TY - JOUR T1 - Positive and strongly relaxed purifying selection drive the evolution of repeats in proteins JF - Nature Communications Y1 - 2016 A1 - Persi, Erez A1 - Wolf, Yuri I. A1 - Koonin, Eugene V VL - 7 UR - http://www.nature.com/doifinder/10.1038/ncomms13570 J1 - Nat Comms M3 - 10.1038/ncomms13570 ER - TY - JOUR T1 - Privacy-Preserving Microbiome Analysis Using Secure Computation JF - Bioinformatics Y1 - 2016 A1 - Wagner, Justin A1 - Paulson, Joseph N. A1 - Wang, Xiao A1 - Bhattacharjee, Bobby A1 - Bravo, éctor Corrada UR - http://bioinformatics.oxfordjournals.org/lookup/doi/10.1093/bioinformatics/btw073 J1 - Bioinformatics M3 - 10.1093/bioinformatics/btw073 ER - TY - JOUR T1 - The Role of Temporal Trends in Growing Networks. JF - PLoS One Y1 - 2016 A1 - Mokryn, Osnat A1 - Wagner, Allon A1 - Blattner, Marcel A1 - Ruppin, Eytan A1 - Shavitt, Yuval AB -

The rich get richer principle, manifested by the Preferential attachment (PA) mechanism, is widely considered one of the major factors in the growth of real-world networks. PA stipulates that popular nodes are bound to be more attractive than less popular nodes; for example, highly cited papers are more likely to garner further citations. However, it overlooks the transient nature of popularity, which is often governed by trends. Here, we show that in a wide range of real-world networks the recent popularity of a node, i.e., the extent by which it accumulated links recently, significantly influences its attractiveness and ability to accumulate further links. We proceed to model this observation with a natural extension to PA, named Trending Preferential Attachment (TPA), in which edges become less influential as they age. TPA quantitatively parametrizes a fundamental network property, namely the network's tendency to trends. Through TPA, we find that real-world networks tend to be moderately to highly trendy. Networks are characterized by different susceptibilities to trends, which determine their structure to a large extent. Trendy networks display complex structural traits, such as modular community structure and degree-assortativity, occurring regularly in real-world networks. In summary, this work addresses an inherent trait of complex networks, which greatly affects their growth and structure, and develops a unified model to address its interaction with preferential attachment.

VL - 11 CP - 8 M3 - 10.1371/journal.pone.0156505 ER - TY - RPRT T1 - Scaffolding of long read assemblies using long range contact information Y1 - 2016 A1 - Ghurye, Jay A1 - Pop, Mihai A1 - Koren, Sergey A1 - Chin, Chen-Shan UR - http://biorxiv.org/lookup/doi/10.1101/083964 M3 - 10.1101/083964 ER - TY - JOUR T1 - Systems-Wide Prediction of Enzyme Promiscuity Reveals a New Underground Alternative Route for Pyridoxal 5'-Phosphate Production in E. coli. JF - PLoS Comput Biol Y1 - 2016 A1 - Oberhardt, Matthew A A1 - Zarecki, Raphy A1 - Reshef, Leah A1 - Xia, Fangfang A1 - Duran-Frigola, Miquel A1 - Schreiber, Rachel A1 - Henry, Christopher S A1 - Ben-Tal, Nir A1 - Dwyer, Daniel J A1 - Gophna, Uri A1 - Ruppin, Eytan AB -

Recent insights suggest that non-specific and/or promiscuous enzymes are common and active across life. Understanding the role of such enzymes is an important open question in biology. Here we develop a genome-wide method, PROPER, that uses a permissive PSI-BLAST approach to predict promiscuous activities of metabolic genes. Enzyme promiscuity is typically studied experimentally using multicopy suppression, in which over-expression of a promiscuous 'replacer' gene rescues lethality caused by inactivation of a 'target' gene. We use PROPER to predict multicopy suppression in Escherichia coli, achieving highly significant overlap with published cases (hypergeometric p = 4.4e-13). We then validate three novel predicted target-replacer gene pairs in new multicopy suppression experiments. We next go beyond PROPER and develop a network-based approach, GEM-PROPER, that integrates PROPER with genome-scale metabolic modeling to predict promiscuous replacements via alternative metabolic pathways. GEM-PROPER predicts a new indirect replacer (thiG) for an essential enzyme (pdxB) in production of pyridoxal 5'-phosphate (the active form of Vitamin B6), which we validate experimentally via multicopy suppression. We perform a structural analysis of thiG to determine its potential promiscuous active site, which we validate experimentally by inactivating the pertaining residues and showing a loss of replacer activity. Thus, this study is a successful example where a computational investigation leads to a network-based identification of an indirect promiscuous replacement of a key metabolic enzyme, which would have been extremely difficult to identify directly.

VL - 12 CP - 1 M3 - 10.1371/journal.pcbi.1004705 ER - TY - JOUR T1 - System-wide Clinical Proteomics of Breast Cancer Reveals Global Remodeling of Tissue Homeostasis. JF - Cell Syst Y1 - 2016 A1 - Pozniak, Yair A1 - Balint-Lahat, Nora A1 - Rudolph, Jan Daniel A1 - Lindskog, Cecilia A1 - Katzir, Rotem A1 - Avivi, Camilla A1 - Pontén, Fredrik A1 - Ruppin, Eytan A1 - Barshack, Iris A1 - Geiger, Tamar AB -

The genomic and transcriptomic landscapes of breast cancer have been extensively studied, but the proteomes of breast tumors are far less characterized. Here, we use high-resolution, high-accuracy mass spectrometry to perform a deep analysis of luminal-type breast cancer progression using clinical breast samples from primary tumors, matched lymph node metastases, and healthy breast epithelia. We used a super-SILAC mix to quantify over 10,000 proteins with high accuracy, enabling us to identify key proteins and pathways associated with tumorigenesis and metastatic spread. We found high expression levels of proteins associated with protein synthesis and degradation in cancer tissues, accompanied by metabolic alterations that may facilitate energy production in cancer cells within their natural environment. In addition, we found proteomic differences between breast cancer stages and minor differences between primary tumors and their matched lymph node metastases. These results highlight the potential of proteomic technology in the elucidation of clinically relevant cancer signatures.

VL - 2 CP - 3 M3 - 10.1016/j.cels.2016.02.001 ER - TY - JOUR T1 - Therapeutic relevance of the protein phosphatase 2A in cancer JF - Oncotarget.com Y1 - 2016 A1 - Cunningham, Chelsea E. A1 - Li, Shuangshuang A1 - Vizeacoumar, Frederick S. A1 - Bhanumathy, Kalpana Kalyanasundaram A1 - Lee, Joo Sang A1 - Parameswaran, Sreejit A1 - Furber, Levi A1 - Abuhussein, Omar A1 - Paul, James M. A1 - McDonald, Megan A1 - Templeton, Shaina D. A1 - Shukla, Hersh A1 - El Zawily, Amr M. A1 - Boyd, Frederick A1 - Alli, Nezeka A1 - Mousseau, Darrell D. A1 - Geyer, Ron A1 - Bonham, Keith A1 - Anderson, Deborah H. A1 - Yan, Jiong A1 - Yu-Lee, Li-Yuan A1 - Weaver, Beth A. A1 - Uppalapati, Maruti A1 - Ruppin, Eytan A1 - Sablina, Anna A1 - Freywald, Andrew A1 - Vizeacoumar, Franco J. UR - https://www.oncotarget.com/article/11399 J1 - Oncotarget M3 - 10.18632/oncotarget.11399 ER - TY - JOUR T1 - Transcriptome Remodeling in Trypanosoma cruzi and Human Cells during Intracellular Infection. JF - PLoS Pathog Y1 - 2016 A1 - Li, Yuan A1 - Shah-Simpson, Sheena A1 - Okrah, Kwame A1 - Belew, A Trey A1 - Choi, Jungmin A1 - Caradonna, Kacey L A1 - Padmanabhan, Prasad A1 - Ndegwa, David M A1 - Temanni, M Ramzi A1 - Corrada Bravo, Hector A1 - El-Sayed, Najib M A1 - Burleigh, Barbara A AB -

Intracellular colonization and persistent infection by the kinetoplastid protozoan parasite, Trypanosoma cruzi, underlie the pathogenesis of human Chagas disease. To obtain global insights into the T. cruzi infective process, transcriptome dynamics were simultaneously captured in the parasite and host cells in an infection time course of human fibroblasts. Extensive remodeling of the T. cruzi transcriptome was observed during the early establishment of intracellular infection, coincident with a major developmental transition in the parasite. Contrasting this early response, few additional changes in steady state mRNA levels were detected once mature T. cruzi amastigotes were formed. Our findings suggest that transcriptome remodeling is required to establish a modified template to guide developmental transitions in the parasite, whereas homeostatic functions are regulated independently of transcriptomic changes, similar to that reported in related trypanosomatids. Despite complex mechanisms for regulation of phenotypic expression in T. cruzi, transcriptomic signatures derived from distinct developmental stages mirror known or projected characteristics of T. cruzi biology. Focusing on energy metabolism, we were able to validate predictions forecast in the mRNA expression profiles. We demonstrate measurable differences in the bioenergetic properties of the different mammalian-infective stages of T. cruzi and present additional findings that underscore the importance of mitochondrial electron transport in T. cruzi amastigote growth and survival. Consequences of T. cruzi colonization for the host include dynamic expression of immune response genes and cell cycle regulators with upregulation of host cholesterol and lipid synthesis pathways, which may serve to fuel intracellular T. cruzi growth. Thus, in addition to the biological inferences gained from gene ontology and functional enrichment analysis of differentially expressed genes in parasite and host, our comprehensive, high resolution transcriptomic dataset provides a substantially more detailed interpretation of T. cruzi infection biology and offers a basis for future drug and vaccine discovery efforts.

VL - 12 CP - 4 M3 - 10.1371/journal.ppat.1005511 ER - TY - ABST T1 - Algorithms in Bioinformatics: 15th International Workshop, WABI 2015 Y1 - 2015 A1 - Pop, Mihai A1 - Touzet, Hélène ED - Istrail, Sorin ED - Pevzner, Pavel ED - Waterman, Michael S JA - Lecture Notes in Bioinformatics PB - Springer SN - 978-3-662-48220-9 ER - TY - JOUR T1 - Bayesian integration of genetics and epigenetics detects causal regulatory SNPs underlying expression variability JF - Nature Communications Y1 - 2015 A1 - Das, Avinash A1 - Morley, Michael A1 - Moravec, Christine S. A1 - Tang, W. H. W. A1 - Hakonarson, Hakon A1 - Ashley, Euan A. A1 - Brandimarto, Jeffrey A1 - Hu, Ray A1 - Li, Mingyao A1 - Li, Hongzhe A1 - Liu, Yichuan A1 - Qu, Liming A1 - Sanchez, Pablo A1 - Margulies, Kenneth B. A1 - Cappola, Thomas P. A1 - Jensen, Shane A1 - Hannenhalli, Sridhar VL - 6 UR - http://www.nature.com/doifinder/10.1038/ncomms9555 J1 - Nat Comms M3 - 10.1038/ncomms9555 ER - TY - CONF T1 - Chromatin and genomic determinants of alternative splicing T2 - BCB '15 Proceedings of the 6th ACM Conference on Bioinformatics, Computational Biology and Health Informatics Y1 - 2015 A1 - Kun Wang A1 - Kan Cao A1 - Sridhar Hannenhalli JA - BCB '15 Proceedings of the 6th ACM Conference on Bioinformatics, Computational Biology and Health Informatics PB - ACM ER - TY - CONF T1 - Computational challenges in microbiome research T2 - 2015 IEEE International Conference on Bioinformatics and Biomedicine (BIBM)2015 IEEE International Conference on Bioinformatics and Biomedicine (BIBM) Y1 - 2015 A1 - Pop, Mihai JA - 2015 IEEE International Conference on Bioinformatics and Biomedicine (BIBM)2015 IEEE International Conference on Bioinformatics and Biomedicine (BIBM) PB - IEEE CY - Washington, DC, USA UR - http://ieeexplore.ieee.org/lpdocs/epic03/wrapper.htm?arnumber=7359645 M3 - 10.1109/BIBM.2015.7359645 ER - TY - JOUR T1 - Diversion of aspartate in ASS1-deficient tumours fosters de novo pyrimidine synthesis JF - Nature Y1 - 2015 A1 - Rabinovich, Shiran A1 - Adler, Lital A1 - Yizhak, Keren A1 - Sarver, Alona A1 - Silberman, Alon A1 - Agron, Shani A1 - Stettner, Noa A1 - Sun, Qin A1 - Brandis, Alexander A1 - Helbling, Daniel A1 - Korman, Stanley A1 - Itzkovitz, Shalev A1 - Dimmock, David A1 - Ulitsky, Igor A1 - Nagamani, Sandesh C. S. A1 - Ruppin, Eytan A1 - Erez, Ayelet VL - 527 UR - http://www.nature.com/doifinder/10.1038/nature15529 CP - 7578 J1 - Nature M3 - 10.1038/nature15529 ER - TY - JOUR T1 - Drugs that reverse disease transcriptomic signatures are more effective in a mouse model of dyslipidemia. JF - Mol Syst Biol Y1 - 2015 A1 - Wagner, Allon A1 - Cohen, Noa A1 - Kelder, Thomas A1 - Amit, Uri A1 - Liebman, Elad A1 - Steinberg, David M A1 - Radonjic, Marijana A1 - Ruppin, Eytan AB -

High-throughput omics have proven invaluable in studying human disease, and yet day-to-day clinical practice still relies on physiological, non-omic markers. The metabolic syndrome, for example, is diagnosed and monitored by blood and urine indices such as blood cholesterol levels. Nevertheless, the association between the molecular and the physiological manifestations of the disease, especially in response to treatment, has not been investigated in a systematic manner. To this end, we studied a mouse model of diet-induced dyslipidemia and atherosclerosis that was subject to various drug treatments relevant to the disease in question. Both physiological data and gene expression data (from the liver and white adipose) were analyzed and compared. We find that treatments that restore gene expression patterns to their norm are associated with the successful restoration of physiological markers to their baselines. This holds in a tissue-specific manner—treatments that reverse the transcriptomic signatures of the disease in a particular tissue are associated with positive physiological effects in that tissue. Further, treatments that introduce large non-restorative gene expression alterations are associated with unfavorable physiological outcomes. These results provide a sound basis to in silico methods that rely on omic metrics for drug repurposing and drug discovery by searching for compounds that reverse a disease’s omic signatures. Moreover, they highlight the need to develop drugs that restore the global cellular state to its healthy norm rather than rectify particular disease phenotypes.

VL - 11 CP - 3 ER - TY - Generic T1 - The effects of telomere shortening on cancer cells: a network model of proteomic and microRNA analysis. Y1 - 2015 A1 - Uziel, O A1 - Yosef, N A1 - Sharan, R A1 - Ruppin, E A1 - Kupiec, M A1 - Kushnir, M A1 - Beery, E A1 - Cohen-Diker, T A1 - Nordenberg, J A1 - Lahav, M KW - Gene Expression Regulation, Neoplastic KW - Gene Regulatory Networks KW - HUMANS KW - MicroRNAs KW - Neoplasms KW - Oligonucleotides KW - Proteome KW - proteomics KW - Telomere Shortening KW - Tumor Cells, Cultured AB -

Previously, we have shown that shortening of telomeres by telomerase inhibition sensitized cancer cells to cisplatinum, slowed their migration, increased DNA damage and impaired DNA repair. The mechanism behind these effects is not fully characterized. Its clarification could facilitate novel therapeutics development and may obviate the time consuming process of telomere shortening achieved by telomerase inhibition. Here we aimed to decipher the microRNA and proteomic profiling of cancer cells with shortened telomeres and identify the key mediators in telomere shortening-induced damage to those cells. Of 870 identified proteins, 98 were differentially expressed in shortened-telomere cells. 47 microRNAs were differentially expressed in these cells; some are implicated in growth arrest or act as oncogene repressors. The obtained data was used for a network construction, which provided us with nodal candidates that may mediate the shortened-telomere dependent features. These proteins' expression was experimentally validated, supporting their potential central role in this system.

JA - Genomics VL - 105 CP - 1 M3 - 10.1016/j.ygeno.2014.10.013 ER - TY - BOOK T1 - Encyclopedia of MetagenomicsHuman Microbiome, Assembly and Analysis Software, Project Y1 - 2015 A1 - Pop, Mihai ED - Highlander, Sarah K. ED - Rodriguez-Valera, Francisco ED - White, Bryan A. PB - Springer US CY - Boston, MA SN - 978-1-4899-7474-7 UR - http://link.springer.com/10.1007/978-1-4899-7475-4http://link.springer.com/content/pdf/10.1007/978-1-4899-7475-4http://link.springer.com/10.1007/978-1-4899-7475-4_87http://link.springer.com/content/pdf/10.1007/978-1-4899-7475-4_87 M3 - 10.1007/978-1-4899-7475-410.1007/978-1-4899-7475-4_87 ER - TY - Generic T1 - Epiviz: a view inside the design of an integrated visual analysis software for genomics Y1 - 2015 A1 - Chelaru, Florin A1 - Corrada Bravo, éctor JA - BMC Bioinformatics VL - 16 UR - http://www.biomedcentral.com/1471-2105/16/S11/S4 CP - Suppl 11 J1 - BMC BioinformaticsBMC Bioinformatics M3 - 10.1186/1471-2105-16-S11-S4 ER - TY - JOUR T1 - Essential Genes in the Core Genome of the Human Pathogen Streptococcus pyogenes. JF - Sci Rep Y1 - 2015 A1 - Le Breton, Yoann A1 - Belew, Ashton T A1 - Valdes, Kayla M A1 - Islam, Emrul A1 - Curry, Patrick A1 - Tettelin, Hervé A1 - Shirtliff, Mark E A1 - El-Sayed, Najib M A1 - McIver, Kevin S AB -

Streptococcus pyogenes (Group A Streptococcus, GAS) remains a major public health burden worldwide, infecting over 750 million people leading to over 500,000 deaths annually. GAS pathogenesis is complex, involving genetically distinct GAS strains and multiple infection sites. To overcome fastidious genetic manipulations and accelerate pathogenesis investigations in GAS, we developed a mariner-based system (Krmit) for en masse monitoring of complex mutant pools by transposon sequencing (Tn-seq). Highly saturated transposant libraries (Krmit insertions in ca. every 25 nucleotides) were generated in two distinct GAS clinical isolates, a serotype M1T1 invasive strain 5448 and a nephritogenic serotype M49 strain NZ131, and analyzed using a Bayesian statistical model to predict GAS essential genes, identifying sets of 227 and 241 of those genes in 5448 and NZ131, respectively. A large proportion of GAS essential genes corresponded to key cellular processes and metabolic pathways, and 177 were found conserved within the GAS core genome established from 20 available GAS genomes. Selected essential genes were validated using conditional-expression mutants. Finally, comparison to previous essentiality analyses in S. sanguinis and S. pneumoniae revealed significant overlaps, providing valuable insights for the development of new antimicrobials to treat infections by GAS and other pathogenic streptococci.

VL - 5 M3 - 10.1038/srep09838 ER - TY - Generic T1 - Evaluation of BLAST-based edge-weighting metrics used for homology inference with the Markov Clustering algorithm. Y1 - 2015 A1 - Gibbons, Theodore R A1 - Mount, Stephen M A1 - Cooper, Endymion D A1 - Delwiche, Charles F AB -

BACKGROUND: Clustering protein sequences according to inferred homology is a fundamental step in the analysis of many large data sets. Since the publication of the Markov Clustering (MCL) algorithm in 2002, it has been the centerpiece of several popular applications. Each of these approaches generates an undirected graph that represents sequences as nodes connected to each other by edges weighted with a BLAST-based metric. MCL is then used to infer clusters of homologous proteins by analyzing these graphs. The various approaches differ only by how they weight the edges, yet there has been very little direct examination of the relative performance of alternative edge-weighting metrics. This study compares the performance of four BLAST-based edge-weighting metrics: the bit score, bit score ratio (BSR), bit score over anchored length (BAL), and negative common log of the expectation value (NLE). Performance is tested using the Extended CEGMA KOGs (ECK) database, which we introduce here.

RESULTS: All metrics performed similarly when analyzing full-length sequences, but dramatic differences emerged as progressively larger fractions of the test sequences were split into fragments. The BSR and BAL successfully rescued subsets of clusters by strengthening certain types of alignments between fragmented sequences, but also shifted the largest correct scores down near the range of scores generated from spurious alignments. This penalty outweighed the benefits in most test cases, and was greatly exacerbated by increasing the MCL inflation parameter, making these metrics less robust than the bit score or the more popular NLE. Notably, the bit score performed as well or better than the other three metrics in all scenarios.

CONCLUSIONS: The results provide a strong case for use of the bit score, which appears to offer equivalent or superior performance to the more popular NLE. The insight that MCL-based clustering methods can be improved using a more tractable edge-weighting metric will greatly simplify future implementations. We demonstrate this with our own minimalist Python implementation: Porthos, which uses only standard libraries and can process a graph with 25 m + edges connecting the 60 k + KOG sequences in half a minute using less than half a gigabyte of memory.

JA - BMC Bioinformatics VL - 16 M3 - 10.1186/s12859-015-0625-x ER - TY - JOUR T1 - Evolutionarily conserved network properties of intrinsically disordered proteins. JF - PLoS One Y1 - 2015 A1 - Rangarajan, Nivedita A1 - Kulkarni, Prakash A1 - Hannenhalli, Sridhar KW - Animals KW - Cluster Analysis KW - Databases, Protein KW - Drosophila KW - Drosophila Proteins KW - Evolution, Molecular KW - HUMANS KW - Intrinsically Disordered Proteins KW - Metabolic Networks and Pathways KW - Mice KW - Osmotic Pressure KW - Protein Interaction Maps KW - Saccharomyces cerevisiae KW - Saccharomyces cerevisiae Proteins AB -

BACKGROUND: Intrinsically disordered proteins (IDPs) lack a stable tertiary structure in isolation. Remarkably, however, a substantial portion of IDPs undergo disorder-to-order transitions upon binding to their cognate partners. Structural flexibility and binding plasticity enable IDPs to interact with a broad range of partners. However, the broader network properties that could provide additional insights into the functional role of IDPs are not known.

RESULTS: Here, we report the first comprehensive survey of network properties of IDP-induced sub-networks in multiple species from yeast to human. Our results show that IDPs exhibit greater-than-expected modularity and are connected to the rest of the protein interaction network (PIN) via proteins that exhibit the highest betweenness centrality and connect to fewer-than-expected IDP communities, suggesting that they form critical communication links from IDP modules to the rest of the PIN. Moreover, we found that IDPs are enriched at the top level of regulatory hierarchy.

CONCLUSION: Overall, our analyses reveal coherent and remarkably conserved IDP-centric network properties, namely, modularity in IDP-induced network and a layer of critical nodes connecting IDPs with the rest of the PIN.

VL - 10 CP - 5 M3 - 10.1371/journal.pone.0126729 ER - TY - Generic T1 - Evolutionary Conservation of Bacterial Essential Metabolic Genes across All Bacterial Culture Media Y1 - 2015 A1 - Ish-Am, Oren A1 - Kristensen, David M. A1 - Ruppin, Eytan ED - Thangaraj, Kumarasamy JA - PLOS ONE VL - 10 UR - http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0123785 CP - 4 J1 - PLoS ONE M3 - 10.1371/journal.pone.0123785 ER - TY - Generic T1 - Fumarate induces redox-dependent senescence by modifying glutathione metabolism. Y1 - 2015 A1 - Zheng, Liang A1 - Cardaci, Simone A1 - Jerby, Livnat A1 - MacKenzie, Elaine D A1 - Sciacovelli, Marco A1 - Johnson, T Isaac A1 - Gaude, Edoardo A1 - King, Ayala A1 - Leach, Joshua D G A1 - Edrada-Ebel, RuAngelie A1 - Hedley, Ann A1 - Morrice, Nicholas A A1 - Kalna, Gabriela A1 - Blyth, Karen A1 - Ruppin, Eytan A1 - Frezza, Christian A1 - Gottlieb, Eyal AB -

Mutations in the tricarboxylic acid (TCA) cycle enzyme fumarate hydratase (FH) are associated with a highly malignant form of renal cancer. We combined analytical chemistry and metabolic computational modelling to investigate the metabolic implications of FH loss in immortalized and primary mouse kidney cells. Here, we show that the accumulation of fumarate caused by the inactivation of FH leads to oxidative stress that is mediated by the formation of succinicGSH, a covalent adduct between fumarate and glutathione. Chronic succination of GSH, caused by the loss of FH, or by exogenous fumarate, leads to persistent oxidative stress and cellular senescence in vitro and in vivo. Importantly, the ablation of p21, a key mediator of senescence, in Fh1-deficient mice resulted in the transformation of benign renal cysts into a hyperplastic lesion, suggesting that fumarate-induced senescence needs to be bypassed for the initiation of renal cancers.

JA - Nat Commun VL - 6 M3 - 10.1038/ncomms7001 ER - TY - Generic T1 - Gene Expression Signatures Based on Variability can Robustly Predict Tumor Progression and Prognosis. Y1 - 2015 A1 - Dinalankara, Wikum A1 - Bravo, Héctor Corrada AB -

Gene expression signatures are commonly used to create cancer prognosis and diagnosis methods, yet only a small number of them are successfully deployed in the clinic since many fail to replicate performance on subsequent validation. A primary reason for this lack of reproducibility is the fact that these signatures attempt to model the highly variable and unstable genomic behavior of cancer. Our group recently introduced gene expression anti-profiles as a robust methodology to derive gene expression signatures based on the observation that while gene expression measurements are highly heterogeneous across tumors of a specific cancer type relative to the normal tissue, their degree of deviation from normal tissue expression in specific genes involved in tissue differentiation is a stable tumor mark that is reproducible across experiments and cancer types. Here we show that constructing gene expression signatures based on variability and the anti-profile approach yields classifiers capable of successfully distinguishing benign growths from cancerous growths based on deviation from normal expression. We then show that this same approach generates stable and reproducible signatures that predict probability of relapse and survival based on tumor gene expression. These results suggest that using the anti-profile framework for the discovery of genomic signatures is an avenue leading to the development of reproducible signatures suitable for adoption in clinical settings.

JA - Cancer Inform VL - 14 M3 - 10.4137/CIN.S23862 ER - TY - Generic T1 - The generation of macrophages with anti-inflammatory activity in the absence of STAT6 signaling. Y1 - 2015 A1 - Fleming, Bryan D A1 - Chandrasekaran, Prabha A1 - Dillon, Laura A L A1 - Dalby, Elizabeth A1 - Suresh, Rahul A1 - Sarkar, Arup A1 - El-Sayed, Najib M A1 - Mosser, David M AB -

Macrophages readily change their phenotype in response to exogenous stimuli. In this work, macrophages were stimulated under a variety of experimental conditions, and phenotypic alterations were correlated with changes in gene expression. We identified 3 transcriptionally related populations of macrophages with immunoregulatory activity. They were generated by stimulating cells with TLR ligands in the presence of 3 different "reprogramming" signals: high-density ICs, PGE2, or Ado. All 3 of these cell populations produced high levels of transcripts for IL-10 and growth and angiogenic factors. They also secreted reduced levels of inflammatory cytokines IL-1β, IL-6, and IL-12. All 3 macrophage phenotypes could partially rescue mice from lethal endotoxemia, and therefore, we consider each to have anti-inflammatory activity. This ability to regulate innate-immune responses occurred equally well in macrophages from STAT6-deficient mice. The lack of STAT6 did not affect the ability of macrophages to change cytokine production reciprocally or to rescue mice from lethal endotoxemia. Furthermore, treatment of macrophages with IL-4 failed to induce similar phenotypic or transcriptional alterations. This work demonstrates that there are multiple ways to generate macrophages with immunoregulatory activity. These anti-inflammatory macrophages are transcriptionally and functionally related to each other and are quite distinct from macrophages treated with IL-4.

JA - J Leukoc Biol VL - 98 CP - 3 M3 - 10.1189/jlb.2A1114-560R ER - TY - JOUR T1 - Genomic variation. Impact of regulatory variation from RNA to protein. JF - Science Y1 - 2015 A1 - Battle, Alexis A1 - Khan, Zia A1 - Wang, Sidney H A1 - Mitrano, Amy A1 - Ford, Michael J A1 - Pritchard, Jonathan K A1 - Gilad, Yoav KW - 3' Flanking Region KW - 5' Flanking Region KW - Cell Line KW - Exons KW - Gene Expression Regulation KW - Genetic Variation KW - HUMANS KW - PHENOTYPE KW - Protein Biosynthesis KW - Quantitative Trait Loci KW - Ribosomes KW - RNA, Messenger KW - Transcription, Genetic AB -

The phenotypic consequences of expression quantitative trait loci (eQTLs) are presumably due to their effects on protein expression levels. Yet the impact of genetic variation, including eQTLs, on protein levels remains poorly understood. To address this, we mapped genetic variants that are associated with eQTLs, ribosome occupancy (rQTLs), or protein abundance (pQTLs). We found that most QTLs are associated with transcript expression levels, with consequent effects on ribosome and protein levels. However, eQTLs tend to have significantly reduced effect sizes on protein levels, which suggests that their potential impact on downstream phenotypes is often attenuated or buffered. Additionally, we identified a class of cis QTLs that affect protein abundance with little or no effect on messenger RNA or ribosome levels, which suggests that they may arise from differences in posttranslational regulation.

VL - 347 CP - 6222 M3 - 10.1126/science.1260793 ER - TY - JOUR T1 - Glutamine synthetase activity fuels nucleotide biosynthesis and supports growth of glutamine-restricted glioblastoma JF - Nature Cell Biology Y1 - 2015 A1 - Tardito, Saverio A1 - Oudin, ïs A1 - Ahmed, Shafiq U. A1 - Fack, Fred A1 - Keunen, Olivier A1 - Zheng, Liang A1 - Miletic, Hrvoje A1 - Sakariassen, Øystein A1 - Weinstock, Adam A1 - Wagner, Allon A1 - Lindsay, Susan L. A1 - Hock, Andreas K. A1 - Barnett, Susan C. A1 - Ruppin, Eytan A1 - ørkve, Svein Harald A1 - Lund-Johansen, Morten A1 - Chalmers, Anthony J. A1 - Bjerkvig, Rolf A1 - Niclou, Simone P. A1 - Gottlieb, Eyal VL - 17 UR - http://www.nature.com/doifinder/10.1038/ncb3272 CP - 12 J1 - Nat Cell Biol M3 - 10.1038/ncb3272 ER - TY - JOUR T1 - Harnessing the landscape of microbial culture media to predict new organism-media pairings. JF - Nat Commun Y1 - 2015 A1 - Oberhardt, Matthew A A1 - Zarecki, Raphy A1 - Gronow, Sabine A1 - Lang, Elke A1 - Klenk, Hans-Peter A1 - Gophna, Uri A1 - Ruppin, Eytan AB -

Culturing microorganisms is a critical step in understanding and utilizing microbial life. Here we map the landscape of existing culture media by extracting natural-language media recipes into a Known Media Database (KOMODO), which includes >18,000 strain-media combinations, >3300 media variants and compound concentrations (the entire collection of the Leibniz Institute DSMZ repository). Using KOMODO, we show that although media are usually tuned for individual strains using biologically common salts, trace metals and vitamins/cofactors are the most differentiating components between defined media of strains within a genus. We leverage KOMODO to predict new organism-media pairings using a transitivity property (74% growth in new in vitro experiments) and a phylogeny-based collaborative filtering tool (83% growth in new in vitro experiments and stronger growth on predicted well-scored versus poorly scored media). These resources are integrated into a web-based platform that predicts media given an organism's 16S rDNA sequence, facilitating future cultivation efforts.

VL - 6 M3 - 10.1038/ncomms9493 ER - TY - RPRT T1 - Heterogeneity of Transcription Factor binding specificity models within and across cell lines Y1 - 2015 A1 - Sharmin, Mahfuza A1 - Corrada Bravo, Hector A1 - Hannenhalli, Sridhar S. UR - http://biorxiv.org/lookup/doi/10.1101/028787 M3 - 10.1101/028787 ER - TY - JOUR T1 - High throughput identification of cis-regulatory rewiring events in yeast. JF - Mol Biol Evol Y1 - 2015 A1 - Sarda, Shrutii A1 - Hannenhalli, Sridhar AB -

A co-regulated module of genes ("regulon") can have evolutionarily conserved expression patterns and yet have diverged upstream regulators across species. For instance, the ribosomal genes regulon is regulated by the transcription factor (TF) TBF1 in C. albicans, while in S. cerevisiae it is regulated by RAP1. Only a handful of such rewiring events have been established, and the prevalence or conditions conducive to such events are not well known. Here, we develop a novel probabilistic scoring method to comprehensively screen for regulatory rewiring within regulons across 23 yeast species. Investigation of 1713 regulons and 176 TFs yielded 5353 significant rewiring events at 5% FDR. Besides successfully recapitulating known rewiring events, our analyses also suggests TF candidates for certain processes reported to be under distinct regulatory controls in S. cerevisiae and C. albicans, for which the implied regulators are not known: 1) oxidative stress response (Sc-MSN2 to Ca-FKH2),and 2) nutrient modulation (Sc-RTG1 to Ca-GCN4/Ca-UME6). Further, a stringent screen to detect TF rewiring at individual genes identified 1446 events at 10% FDR. Overall, these events are supported by strong co-expression between the predicted regulator and its target gene(s) in a species-specific fashion (>50-fold). Independent functional analyses of rewiring TF pairs revealed greater functional interactions and shared biological processes between them (p=1e-03).Our study represents the first comprehensive assessment of regulatory rewiring; with a novel approach that has generated a unique high-confidence resource of several specific events, suggesting that evolutionary rewiring is relatively frequent and may be a significant mechanism of regulatory innovation.

M3 - 10.1093/molbev/msv203 ER - TY - Generic T1 - Impact of regulatory variation from RNA to protein Y1 - 2015 A1 - Battle, A. A1 - Khan, Z. A1 - Wang, S. H. A1 - Mitrano, A. A1 - Ford, M. J. A1 - Pritchard, J. K. A1 - Gilad, Y. JA - Science VL - 347 UR - http://www.sciencemag.org/cgi/doi/10.1126/science.1260793 CP - 6222 J1 - Science M3 - 10.1126/science.1260793 ER - TY - Generic T1 - Improved evidence-based genome-scale metabolic models for maize leaf, embryo, and endosperm. Y1 - 2015 A1 - Seaver, Samuel M D A1 - Bradbury, Louis M T A1 - Frelin, Océane A1 - Zarecki, Raphy A1 - Ruppin, Eytan A1 - Hanson, Andrew D A1 - Henry, Christopher S AB -

There is a growing demand for genome-scale metabolic reconstructions for plants, fueled by the need to understand the metabolic basis of crop yield and by progress in genome and transcriptome sequencing. Methods are also required to enable the interpretation of plant transcriptome data to study how cellular metabolic activity varies under different growth conditions or even within different organs, tissues, and developmental stages. Such methods depend extensively on the accuracy with which genes have been mapped to the biochemical reactions in the plant metabolic pathways. Errors in these mappings lead to metabolic reconstructions with an inflated number of reactions and possible generation of unreliable metabolic phenotype predictions. Here we introduce a new evidence-based genome-scale metabolic reconstruction of maize, with significant improvements in the quality of the gene-reaction associations included within our model. We also present a new approach for applying our model to predict active metabolic genes based on transcriptome data. This method includes a minimal set of reactions associated with low expression genes to enable activity of a maximum number of reactions associated with high expression genes. We apply this method to construct an organ-specific model for the maize leaf, and tissue specific models for maize embryo and endosperm cells. We validate our models using fluxomics data for the endosperm and embryo, demonstrating an improved capacity of our models to fit the available fluxomics data. All models are publicly available via the DOE Systems Biology Knowledgebase and PlantSEED, and our new method is generally applicable for analysis transcript profiles from any plant, paving the way for further in silico studies with a wide variety of plant genomes.

JA - Front Plant Sci VL - 6 M3 - 10.3389/fpls.2015.00142 ER - TY - JOUR T1 - Independent Emergence of Artemisinin Resistance Mutations Among Plasmodium falciparum in Southeast Asia JF - Journal of Infectious Diseases Y1 - 2015 A1 - Takala-Harrison, S. A1 - Jacob, C. G. A1 - Arze, C. A1 - Michael P. Cummings A1 - Silva, J. C. A1 - Dondorp, A. M. A1 - Fukuda, M. M. A1 - Hien, T. T. A1 - Mayxay, M. A1 - Noedl, H. A1 - Nosten, F. A1 - Kyaw, M. P. A1 - Nhien, N. T. T. A1 - Imwong, M. A1 - Bethell, D. A1 - Se, Y. A1 - Lon, C. A1 - Tyner, S. D. A1 - Saunders, D. L. A1 - Ariey, F. A1 - Mercereau-Puijalon, O. A1 - Menard, D. A1 - Newton, P. N. A1 - Khanthavong, M. A1 - Hongvanthong, B. A1 - Starzengruber, P. A1 - Fuehrer, H.-P. A1 - Swoboda, P. A1 - Khan, W. A. A1 - Phyo, A. P. A1 - Nyunt, M. M. A1 - Nyunt, M. H. A1 - Brown, T. S. A1 - Adams, M. A1 - Pepin, C. S. A1 - Bailey, J. A1 - Tan, J. C. A1 - Ferdig, M. T. A1 - Clark, T. G. A1 - Miotto, O. A1 - MacInnis, B. A1 - Kwiatkowski, D. P. A1 - White, N. J. A1 - Ringwald, P. A1 - Plowe, CV VL - 211 M3 - 10.1093/infdis/jiu491 ER - TY - Generic T1 - Insights from GWAS: emerging landscape of mechanisms underlying complex trait disease. Y1 - 2015 A1 - Pal, Lipika R A1 - Yu, Chen-Hsin A1 - Mount, Stephen M A1 - Moult, John AB -

BACKGROUND: There are now over 2000 loci in the human genome where genome wide association studies (GWAS) have found one or more SNPs to be associated with altered risk of a complex trait disease. At each of these loci, there must be some molecular level mechanism relevant to the disease. What are these mechanisms and how do they contribute to disease?

RESULTS: Here we consider the roles of three primary mechanism classes: changes that directly alter protein function (missense SNPs), changes that alter transcript abundance as a consequence of variants close-by in sequence, and changes that affect splicing. Missense SNPs are divided into those predicted to have a high impact on in vivo protein function, and those with a low impact. Splicing is divided into SNPs with a direct impact on splice sites, and those with a predicted effect on auxiliary splicing signals. The analysis was based on associations found for seven complex trait diseases in the classic Wellcome Trust Case Control Consortium (WTCCC1) GWA study and subsequent studies and meta-analyses, collected from the GWAS catalog. Linkage disequilibrium information was used to identify possible candidate SNPs for involvement in disease mechanism in each of the 356 loci associated with these seven diseases. With the parameters used, we find that 76% of loci have at least of these mechanisms. Overall, except for the low incidence of direct impact on splice sites, the mechanisms are found at similar frequencies, with changes in transcript abundance the most common. But the distribution of mechanisms over diseases varies markedly, as does the fraction of loci with assigned mechanisms. Many of the implicated proteins have previously been suggested as relevant, but the specific mechanism assignments are new. In addition, a number of new disease relevant proteins are proposed.

CONCLUSIONS: The high fraction of GWAS loci with proposed mechanisms suggests that these classes of mechanism play a major role. Other mechanism types, such as variants affecting expression of genes remote in the DNA sequence, will contribute in other loci. Each of the identified putative mechanisms provides a hypothesis for further investigation.

JA - BMC Genomics VL - 16 Suppl 8 M3 - 10.1186/1471-2164-16-S8-S4 ER - TY - JOUR T1 - Maligner: a fast ordered restriction map aligner JF - Bioinformatics Y1 - 2015 A1 - Mendelowitz, Lee M. A1 - Schwartz, David C. A1 - Pop, Mihai UR - http://bioinformatics.oxfordjournals.org/lookup/doi/10.1093/bioinformatics/btv711 J1 - Bioinformatics M3 - 10.1093/bioinformatics/btv711 ER - TY - JOUR T1 - Microbiota that affect risk for shigellosis in children in low-income countries JF - Emerg Infect DisEmerg Infect Dis Y1 - 2015 A1 - Lindsay, B. A1 - Oundo, J. A1 - Hossain, M. A. A1 - Antonio, M. A1 - Tamboura, B. A1 - Walker, A. W. A1 - Paulson, J. N. A1 - Parkhill, J. A1 - Omore, R. A1 - Faruque, A. S. A1 - Das, S. K. A1 - Ikumapayi, U. N. A1 - Adeyemi, M. A1 - Sanogo, D. A1 - Saha, D. A1 - Sow, S. A1 - Farag, T. H. A1 - Nasrin, D. A1 - Li, S. A1 - Panchalingam, S. A1 - Levine, M. M. A1 - Kotloff, K. A1 - Magder, L. S. A1 - Hungerford, L. A1 - Sommerfelt, H. A1 - Pop, M. A1 - Nataro, J. P. A1 - Stine, O. C. AB - Pathogens in the gastrointestinal tract exist within a vast population of microbes. We examined associations between pathogens and composition of gut microbiota as they relate to Shigella spp./enteroinvasive Escherichia coli infection. We analyzed 3,035 stool specimens (1,735 nondiarrheal and 1,300 moderate-to-severe diarrheal) from the Global Enteric Multicenter Study for 9 enteropathogens. Diarrheal specimens had a higher number of enteropathogens (diarrheal mean 1.4, nondiarrheal mean 0.95; p<0.0001). Rotavirus showed a negative association with Shigella spp. in cases of diarrhea (odds ratio 0.31, 95% CI 0.17-0.55) and had a large combined effect on moderate-to-severe diarrhea (odds ratio 29, 95% CI 3.8-220). In 4 Lactobacillus taxa identified by 16S rRNA gene sequencing, the association between pathogen and disease was decreased, which is consistent with the possibility that Lactobacillus spp. are protective against Shigella spp.-induced diarrhea. Bacterial diversity of gut microbiota was associated with diarrhea status, not high levels of the Shigella spp. ipaH gene. VL - 21 SN - 1080-6059 (Electronic)
1080-6040 (Linking) N1 - Lindsay, Brianna
Oundo, Joe
Hossain, M Anowar
Antonio, Martin
Tamboura, Boubou
Walker, Alan W
Paulson, Joseph N
Parkhill, Julian
Omore, Richard
Faruque, Abu S G
Das, Suman Kumar
Ikumapayi, Usman N
Adeyemi, Mitchell
Sanogo, Doh
Saha, Debasish
Sow, Samba
Farag, Tamer H
Nasrin, Dilruba
Li, Shan
Panchalingam, Sandra
Levine, Myron M
Kotloff, Karen
Magder, Laurence S
Hungerford, Laura
Sommerfelt, Halvor
Pop, Mihai
Nataro, James P
Stine, O Colin
U19 090873/PHS HHS/United States
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
United States
Emerg Infect Dis. 2015 Feb;21(2):242-50. doi: 10.3201/eid2101.140795. U2 - PMC4313639 ER - TY - Generic T1 - Modeling cancer metabolism on a genome scale Y1 - 2015 A1 - Yizhak, K. A1 - Chaneton, B. A1 - Gottlieb, E. A1 - Ruppin, E. JA - Molecular Systems Biology VL - 11 UR - http://msb.embopress.org/cgi/doi/10.15252/msb.20145307 CP - 6 J1 - Molecular Systems Biology M3 - 10.15252/msb.20145307 ER - TY - JOUR T1 - A molecular phylogeny for the oldest (nonditrysian) lineages of extant Lepidoptera, with implications for classification, comparative morphology and life-history evolution JF - Systematic Entomology Y1 - 2015 A1 - Regier, Jerome C A1 - Mitter, Charles A1 - KRISTENSEN, NIELS P. A1 - Davis, Donald R. A1 - VAN NIEUKERKEN, ERIK J. A1 - ROTA, JADRANKA A1 - Simonsen, Thomas J. A1 - Mitter, Kim T. A1 - Kawahara, Akito Y. A1 - Yen, Shen-Horn A1 - Michael P. Cummings A1 - Zwick, Andreas M3 - 10.1111/syen.12129 ER - TY - Generic T1 - Moving ahead on harnessing synthetic lethality to fight cancer Y1 - 2015 A1 - Jerby-Arnon, Livnat A1 - Ruppin, Eytan JA - Molecular & Cellular Oncology VL - 2 UR - http://www.tandfonline.com/doi/abs/10.4161/23723556.2014.977150 CP - 2 J1 - Molecular & Cellular Oncology M3 - 10.4161/23723556.2014.977150 ER - TY - Generic T1 - Orchestrating high-throughput genomic analysis with Bioconductor. Y1 - 2015 A1 - Huber, Wolfgang A1 - Carey, Vincent J A1 - Gentleman, Robert A1 - Anders, Simon A1 - Carlson, Marc A1 - Carvalho, Benilton S A1 - Bravo, Héctor Corrada A1 - Davis, Sean A1 - Gatto, Laurent A1 - Girke, Thomas A1 - Gottardo, Raphael A1 - Hahne, Florian A1 - Hansen, Kasper D A1 - Irizarry, Rafael A A1 - Lawrence, Michael A1 - Love, Michael I A1 - MacDonald, James A1 - Obenchain, Valerie A1 - Oleś, Andrzej K A1 - Pagès, Hervé A1 - Reyes, Alejandro A1 - Shannon, Paul A1 - Smyth, Gordon K A1 - Tenenbaum, Dan A1 - Waldron, Levi A1 - Morgan, Martin KW - Computational Biology KW - Gene Expression Profiling KW - Genomics KW - High-Throughput Screening Assays KW - Programming Languages KW - software KW - User-Computer Interface AB -

Bioconductor is an open-source, open-development software project for the analysis and comprehension of high-throughput data in genomics and molecular biology. The project aims to enable interdisciplinary research, collaboration and rapid development of scientific software. Based on the statistical programming language R, Bioconductor comprises 934 interoperable packages contributed by a large, diverse community of scientists. Packages cover a range of bioinformatic and statistical applications. They undergo formal initial review and continuous automated testing. We present an overview for prospective users and contributors.

JA - Nat Methods VL - 12 CP - 2 M3 - 10.1038/nmeth.3252 ER - TY - Generic T1 - Phenotype-Dependent Coexpression Gene Clusters: Application to Normal and Premature Ageing Y1 - 2015 A1 - Wang, Kun A1 - Das, Avinash A1 - Xiong, Zheng-Mei A1 - Cao, Kan A1 - Hannenhalli, Sridhar JA - IEEE/ACM Transactions on Computational Biology and Bioinformatics VL - 12 UR - http://ieeexplore.ieee.org/lpdocs/epic03/wrapper.htm?arnumber=6948331http://xplorestaging.ieee.org/iel7/8857/7035191/06948331.pdf?arnumber=6948331 CP - 1 J1 - IEEE/ACM Trans. Comput. Biol. and Bioinf. M3 - 10.1109/TCBB.2014.2359446 ER - TY - JOUR T1 - Plasmodium falciparum field isolates from areas of repeated emergence of drug resistant malaria show no evidence of hypermutator phenotype JF - Infection, Genetics and Evolution Y1 - 2015 A1 - Brown, Tyler S. A1 - Jacob, Christopher G A1 - Silva, Joana C A1 - Takala-Harrison, Shannon A1 - Djimdé, Abdoulaye A1 - Dondorp, Arjen M A1 - Fukuda, Mark A1 - Noedl, Harald A1 - Nyunt, Myaing Myaing A1 - Kyaw, Myat Phone A1 - Mayxay, Mayfong A1 - Hien, Tran Tinh A1 - Plowe, Christopher V A1 - Michael P. Cummings VL - 30 M3 - 10.1016/j.meegid.2014.12.010 ER - TY - RPRT T1 - Privacy-Preserving Microbiome Analysis Using Secure Computation Y1 - 2015 A1 - Wagner, Justin A1 - Paulson, Joseph N. A1 - Wang, Xiao-Shun A1 - Bhattacharjee, Bobby A1 - Corrada Bravo, Hector UR - http://biorxiv.org/lookup/doi/10.1101/025999 M3 - 10.1101/025999 ER - TY - Generic T1 - Proteomics-based metabolic modeling reveals that fatty acid oxidation (FAO) controls endothelial cell (EC) permeability. Y1 - 2015 A1 - Patella, Francesca A1 - Schug, Zachary T A1 - Persi, Erez A1 - Neilson, Lisa J A1 - Erami, Zahra A1 - Avanzato, Daniele A1 - Maione, Federica A1 - Hernandez-Fernaud, Juan R A1 - Mackay, Gillian A1 - Zheng, Liang A1 - Reid, Steven A1 - Frezza, Christian A1 - Giraudo, Enrico A1 - Fiorio Pla, Alessandra A1 - Anderson, Kurt A1 - Ruppin, Eytan A1 - Gottlieb, Eyal A1 - Zanivan, Sara AB -

Endothelial cells (ECs) play a key role to maintain the functionality of blood vessels. Altered EC permeability causes severe impairment in vessel stability and is a hallmark of pathologies such as cancer and thrombosis. Integrating label-free quantitative proteomics data into genome-wide metabolic modeling, we built up a model that predicts the metabolic fluxes in ECs when cultured on a tridimensional matrix and organize into a vascular-like network. We discovered how fatty acid oxidation increases when ECs are assembled into a fully formed network that can be disrupted by inhibiting CPT1A, the fatty acid oxidation rate-limiting enzyme. Acute CPT1A inhibition reduces cellular ATP levels and oxygen consumption, which are restored by replenishing the tricarboxylic acid cycle. Remarkably, global phosphoproteomic changes measured upon acute CPT1A inhibition pinpointed altered calcium signaling. Indeed, CPT1A inhibition increases intracellular calcium oscillations. Finally, inhibiting CPT1A induces hyperpermeability in vitro and leakage of blood vessel in vivo, which were restored blocking calcium influx or replenishing the tricarboxylic acid cycle. Fatty acid oxidation emerges as central regulator of endothelial functions and blood vessel stability and druggable pathway to control pathological vascular permeability.

JA - Mol Cell Proteomics VL - 14 CP - 3 M3 - 10.1074/mcp.M114.045575 ER - TY - JOUR T1 - Recognizing the 35th anniversary of the proposal that snRNPs are involved in splicing. JF - Mol Biol Cell Y1 - 2015 A1 - Mount, Stephen M A1 - Wolin, Sandra L AB -

Thirty-five years ago, as young graduate students, we had the pleasure and privilege of being in Joan Steitz's laboratory at a pivotal point in the history of RNA molecular biology. Introns had recently been discovered in the laboratories of Philip Sharp and Richard Roberts, but the machinery for removing them from mRNA precursors was entirely unknown. This Retrospective describes our hypothesis that recently discovered snRNPs functioned in pre-mRNA splicing. The proposal was proven correct, as has Joan's intuition that small RNAs provide specificity to RNA processing reactions through base pairing in diverse settings. However, research over the intervening years has revealed that both splice site selection and splicing itself are much more complex and dynamic than we imagined.

VL - 26 CP - 20 M3 - 10.1091/mbc.E14-10-1486 ER - TY - JOUR T1 - Regulated CRISPR Modules Exploit a Dual Defense Strategy of Restriction and Abortive Infection in a Model of Prokaryote-Phage Coevolution. JF - PLoS Comput Biol Y1 - 2015 A1 - Kumar, M Senthil A1 - Plotkin, Joshua B A1 - Hannenhalli, Sridhar AB -

CRISPRs offer adaptive immunity in prokaryotes by acquiring genomic fragments from infecting phage and subsequently exploiting them for phage restriction via an RNAi-like mechanism. Here, we develop and analyze a dynamical model of CRISPR-mediated prokaryote-phage coevolution that incorporates classical CRISPR kinetics along with the recently discovered infection-induced activation and autoimmunity side effects. Our analyses reveal two striking characteristics of the CRISPR defense strategy: that both restriction and abortive infections operate during coevolution with phages, driving phages to much lower densities than possible with restriction alone, and that CRISPR maintenance is determined by a key dimensionless combination of parameters, which upper bounds the activation level of CRISPRs in uninfected populations. We contrast these qualitative observations with experimental data on CRISPR kinetics, which offer insight into the spacer deletion mechanism and the observed low CRISPR prevalence in clinical isolates. More generally, we exploit numerical simulations to delineate four regimes of CRISPR dynamics in terms of its host, kinetic, and regulatory parameters.

VL - 11 CP - 11 M3 - 10.1371/journal.pcbi.1004603 ER - TY - JOUR T1 - Relationships within Cladobranchia (Gastropoda: Nudibranchia) based on RNA-Seq data: an initial investigation JF - Royal Society Open Science Y1 - 2015 A1 - Goodheart, Jessica A1 - Bazinet, Adam L. A1 - Collins, Allen G. A1 - CUMMINGS, MICHAEL P. VL - 23547143619757560685451171766 UR - http://rsos.royalsocietypublishing.org/lookup/doi/10.1098/rsos.150196 CP - 9 J1 - R. Soc. open sci. M3 - 10.1098/rsos.150196 ER - TY - Generic T1 - RNA-Seq identifies novel myocardial gene expression signatures of heart failure. Y1 - 2015 A1 - Liu, Yichuan A1 - Morley, Michael A1 - Brandimarto, Jeffrey A1 - Hannenhalli, Sridhar A1 - Hu, Yu A1 - Ashley, Euan A A1 - Tang, W H Wilson A1 - Moravec, Christine S A1 - Margulies, Kenneth B A1 - Cappola, Thomas P A1 - Li, Mingyao AB -

Heart failure is a complex clinical syndrome and has become the most common reason for adult hospitalization in developed countries. Two subtypes of heart failure, ischemic heart disease (ISCH) and dilated cardiomyopathy (DCM), have been studied using microarray platforms. However, microarray has limited resolution. Here we applied RNA sequencing (RNA-Seq) to identify gene signatures for heart failure from six individuals, including three controls, one ISCH and two DCM patients. Using genes identified from this small RNA-Seq dataset, we were able to accurately classify heart failure status in a much larger set of 313 individuals. The identified genes significantly overlapped with genes identified via genome-wide association studies for cardiometabolic traits and the promoters of those genes were enriched for binding sites for transcriptions factors. Our results indicate that it is possible to use RNA-Seq to classify disease status for complex diseases such as heart failure using an extremely small training dataset.

JA - Genomics VL - 105 CP - 2 M3 - 10.1016/j.ygeno.2014.12.002 ER - TY - JOUR T1 - Robust Parameter Estimation for Biological Systems: A Study on the Dynamics of Microbial Communities JF - arXiv preprint arXiv:1509.06926 Y1 - 2015 A1 - Matthias Chung A1 - Justin Krueger A1 - Mihai Pop ER - TY - Generic T1 - Shape analysis of high-throughput transcriptomics experiment data. Y1 - 2015 A1 - Okrah, Kwame A1 - Corrada Bravo, Hector AB -

The recent growth of high-throughput transcriptome technology has been paralleled by the development of statistical methodologies to analyze the data they produce. Some of these newly developed methods are based on the assumption that the data observed or a transformation of the data are relatively symmetric with light tails, usually summarized by assuming a Gaussian random component. It is indeed very difficult to assess this assumption for small sample sizes. In this article, we utilize L-moments statistics as the basis of exploratory data analysis, the assessment of distributional assumptions, and the hypothesis testing of high-throughput transcriptomic data. In particular, we use L-moments ratios for assessing the shape (skewness and kurtosis) of high-throughput transcriptome data. Based on these statistics, we propose an algorithm for identifying genes with distributions that are markedly different from the majority in the data. In addition, we also illustrate the utility of this framework to characterize the robustness of distributional assumptions. We apply it to RNA-seq data and find that methods based on the simple [Formula: see text]-test for differential expression analysis using L-moments as weights are robust.

JA - Biostatistics VL - 16 CP - 4 M3 - 10.1093/biostatistics/kxv018 ER - TY - JOUR T1 - Simultaneous transcriptional profiling of Leishmania major and its murine macrophage host cell reveals insights into host-pathogen interactions. JF - BMC Genomics Y1 - 2015 A1 - Dillon, Laura A L A1 - Suresh, Rahul A1 - Okrah, Kwame A1 - Corrada Bravo, Hector A1 - Mosser, David M A1 - El-Sayed, Najib M AB -

BACKGROUND: Parasites of the genus Leishmania are the causative agents of leishmaniasis, a group of diseases that range in manifestations from skin lesions to fatal visceral disease. The life cycle of Leishmania parasites is split between its insect vector and its mammalian host, where it resides primarily inside of macrophages. Once intracellular, Leishmania parasites must evade or deactivate the host's innate and adaptive immune responses in order to survive and replicate.

RESULTS: We performed transcriptome profiling using RNA-seq to simultaneously identify global changes in murine macrophage and L. major gene expression as the parasite entered and persisted within murine macrophages during the first 72 h of an infection. Differential gene expression, pathway, and gene ontology analyses enabled us to identify modulations in host and parasite responses during an infection. The most substantial and dynamic gene expression responses by both macrophage and parasite were observed during early infection. Murine genes related to both pro- and anti-inflammatory immune responses and glycolysis were substantially upregulated and genes related to lipid metabolism, biogenesis, and Fc gamma receptor-mediated phagocytosis were downregulated. Upregulated parasite genes included those aimed at mitigating the effects of an oxidative response by the host immune system while downregulated genes were related to translation, cell signaling, fatty acid biosynthesis, and flagellum structure.

CONCLUSIONS: The gene expression patterns identified in this work yield signatures that characterize multiple developmental stages of L. major parasites and the coordinated response of Leishmania-infected macrophages in the real-time setting of a dual biological system. This comprehensive dataset offers a clearer and more sensitive picture of the interplay between host and parasite during intracellular infection, providing additional insights into how pathogens are able to evade host defenses and modulate the biological functions of the cell in order to survive in the mammalian environment.

VL - 16 CP - 1 M3 - 10.1186/s12864-015-2237-2 ER - TY - JOUR T1 - Synthetic dosage lethality in the human metabolic network is highly predictive of tumor growth and cancer patient survival. JF - Proc Natl Acad Sci U S A Y1 - 2015 A1 - Megchelenbrink, Wout A1 - Katzir, Rotem A1 - Lu, Xiaowen A1 - Ruppin, Eytan A1 - Notebaart, Richard A AB -

Synthetic dosage lethality (SDL) denotes a genetic interaction between two genes whereby the underexpression of gene A combined with the overexpression of gene B is lethal. SDLs offer a promising way to kill cancer cells by inhibiting the activity of SDL partners of activated oncogenes in tumors, which are often difficult to target directly. As experimental genome-wide SDL screens are still scarce, here we introduce a network-level computational modeling framework that quantitatively predicts human SDLs in metabolism. For each enzyme pair (A, B) we systematically knock out the flux through A combined with a stepwise flux increase through B and search for pairs that reduce cellular growth more than when either enzyme is perturbed individually. The predictive signal of the emerging network of 12,000 SDLs is demonstrated in five different ways. (i) It can be successfully used to predict gene essentiality in shRNA cancer cell line screens. Moving to clinical tumors, we show that (ii) SDLs are significantly underrepresented in tumors. Furthermore, breast cancer tumors with SDLs active (iii) have smaller sizes and (iv) result in increased patient survival, indicating that activation of SDLs increases cancer vulnerability. Finally, (v) patient survival improves when multiple SDLs are present, pointing to a cumulative effect. This study lays the basis for quantitative identification of cancer SDLs in a model-based mechanistic manner. The approach presented can be used to identify SDLs in species and cell types in which "omics" data necessary for data-driven identification are missing.

M3 - 10.1073/pnas.1508573112 ER - TY - JOUR T1 - Systematics and biogeography of Pleurobranchus  Cuvier, 1804, sea slugs (Heterobranchia: Nudipleura: Pleurobranchidae) JF - Zoological Journal of the Linnean Society Y1 - 2015 A1 - Goodheart, Jessica A1 - Camacho-García, Yolanda A1 - Padula, Vinicius A1 - Schrödl, Michael A1 - Cervera, Juan L. A1 - Gosliner, Terrence M. A1 - Valdés, Ángel AB - Species of Pleurobranchus (Mollusca: Gastropoda: Heterobranchia: Nudipleura: Pleurobranchidae) are commonly found worldwide, but there is a substantial amount of confusion regarding the ranges and identification of individual species. Difficulties in phylogenetic reconstruction and identification of pleurobranchids using morphological traits has resulted in complex classification schemes, with several species having disjunct ranges across physical and biogeographical barriers (including the tropical Indo-Pacific, the eastern Pacific, and the Atlantic). A sizeable number of species of Pleurobranchus has been described; however, many of these species are morphologically and biogeographically similar to others, and probably constitute synonyms. This paper provides a phylogenetic framework of classification for Pleurobranchus based on the mitochondrial genes cytochrome c oxidase I (COI) and 16S rDNA and the nuclear gene histone 3 (H3) using Bayesian and maximum likelihood approaches. Molecular phylogenies obtained recovered most of the well-established species of Pleurobranchus and some morphological characters were found to have taxonomic value for delimiting species in this group. Automatic barcode gap discovery (ABGD) analyses substantiated the distinctiveness of units/species recovered in the phylogenetic analyses, with some exceptions. Morphological descriptions for the 14 species recovered in the molecular phylogeny and discussions on the biogeography and colour variation are included. UR - http://doi.wiley.com/10.1111/zoj.12237 J1 - Zool J Linn Soc M3 - 10.1111/zoj.12237 ER - TY - JOUR T1 - The Theory and Practice of Genome Sequence Assembly JF - Annu Rev Genomics Hum GenetAnnu Rev Genomics Hum Genet Y1 - 2015 A1 - Simpson, J. T. A1 - Pop, M. KW - algorithm KW - Bioinformatics KW - genome sequencing KW - sequence assembly KW - shotgun sequencing AB - The current genomic revolution was made possible by joint advances in genome sequencing technologies and computational approaches for analyzing sequence data. The close interaction between biologists and computational scientists is perhaps most apparent in the development of approaches for sequencing entire genomes, a feat that would not be possible without sophisticated computational tools called genome assemblers (short for genome sequence assemblers). Here, we survey the key developments in algorithms for assembling genome sequences since the development of the first DNA sequencing methods more than 35 years ago. VL - 16 SN - 1545-293X (Electronic)
1527-8204 (Linking) N1 - Simpson, Jared T
Pop, Mihai
eng
2015/05/06 06:00
Annu Rev Genomics Hum Genet. 2015 Aug 24;16:153-72. doi: 10.1146/annurev-genom-090314-050032. Epub 2015 Apr 22. ER - TY - Generic T1 - Transcriptomic profiling of gene expression and RNA processing during Leishmania major differentiation. Y1 - 2015 A1 - Dillon, Laura A L A1 - Okrah, Kwame A1 - Hughitt, V Keith A1 - Suresh, Rahul A1 - Li, Yuan A1 - Fernandes, Maria Cecilia A1 - Belew, A Trey A1 - Corrada Bravo, Hector A1 - Mosser, David M A1 - El-Sayed, Najib M AB -

Protozoan parasites of the genus Leishmania are the etiological agents of leishmaniasis, a group of diseases with a worldwide incidence of 0.9-1.6 million cases per year. We used RNA-seq to conduct a high-resolution transcriptomic analysis of the global changes in gene expression and RNA processing events that occur as L. major transforms from non-infective procyclic promastigotes to infective metacyclic promastigotes. Careful statistical analysis across multiple biological replicates and the removal of batch effects provided a high quality framework for comprehensively analyzing differential gene expression and transcriptome remodeling in this pathogen as it acquires its infectivity. We also identified precise 5' and 3' UTR boundaries for a majority of Leishmania genes and detected widespread alternative trans-splicing and polyadenylation. An investigation of possible correlations between stage-specific preferential trans-splicing or polyadenylation sites and differentially expressed genes revealed a lack of systematic association, establishing that differences in expression levels cannot be attributed to stage-regulated alternative RNA processing. Our findings build on and improve existing expression datasets and provide a substantially more detailed view of L. major biology that will inform the field and potentially provide a stronger basis for drug discovery and vaccine development efforts.

JA - Nucleic Acids Res VL - 43 CP - 14 M3 - 10.1093/nar/gkv656 ER - TY - JOUR T1 - Use and mis-use of supplementary material in science publications JF - BMC Bioinformatics Y1 - 2015 A1 - Pop, Mihai A1 - Salzberg, Steven L. VL - 1632733845166 UR - http://www.biomedcentral.com/1471-2105/16/237http://link.springer.com/content/pdf/10.1186/s12859-015-0668-z CP - 1 J1 - BMC Bioinformatics M3 - 10.1186/s12859-015-0668-z ER - TY - JOUR T1 - Automated ensemble assembly and validation of microbial genomes. JF - BMC Bioinformatics Y1 - 2014 A1 - Koren, Sergey A1 - Todd Treangen A1 - Hill, Christopher M A1 - Pop, Mihai A1 - Phillippy, Adam M KW - Genome, Bacterial KW - Genome, Microbial KW - Genomics KW - Mycobacterium tuberculosis KW - Rhodobacter sphaeroides KW - Sequence Analysis, DNA KW - software AB -

BACKGROUND: The continued democratization of DNA sequencing has sparked a new wave of development of genome assembly and assembly validation methods. As individual research labs, rather than centralized centers, begin to sequence the majority of new genomes, it is important to establish best practices for genome assembly. However, recent evaluations such as GAGE and the Assemblathon have concluded that there is no single best approach to genome assembly. Instead, it is preferable to generate multiple assemblies and validate them to determine which is most useful for the desired analysis; this is a labor-intensive process that is often impossible or unfeasible.

RESULTS: To encourage best practices supported by the community, we present iMetAMOS, an automated ensemble assembly pipeline; iMetAMOS encapsulates the process of running, validating, and selecting a single assembly from multiple assemblies. iMetAMOS packages several leading open-source tools into a single binary that automates parameter selection and execution of multiple assemblers, scores the resulting assemblies based on multiple validation metrics, and annotates the assemblies for genes and contaminants. We demonstrate the utility of the ensemble process on 225 previously unassembled Mycobacterium tuberculosis genomes as well as a Rhodobacter sphaeroides benchmark dataset. On these real data, iMetAMOS reliably produces validated assemblies and identifies potential contamination without user intervention. In addition, intelligent parameter selection produces assemblies of R. sphaeroides comparable to or exceeding the quality of those from the GAGE-B evaluation, affecting the relative ranking of some assemblers.

CONCLUSIONS: Ensemble assembly with iMetAMOS provides users with multiple, validated assemblies for each genome. Although computationally limited to small or mid-sized genomes, this approach is the most effective and reproducible means for generating high-quality assemblies and enables users to select an assembly best tailored to their specific needs.

VL - 15 M3 - 10.1186/1471-2105-15-126 ER - TY - Generic T1 - BlindCall: ultra-fast base-calling of high-throughput sequencing data by blind deconvolution. Y1 - 2014 A1 - Ye, Chengxi A1 - Hsiao, Chiaowen A1 - Corrada Bravo, Hector KW - algorithms KW - High-Throughput Nucleotide Sequencing KW - HUMANS KW - Probability KW - Reproducibility of Results KW - Sequence Analysis, DNA KW - software KW - Time factors AB -

MOTIVATION: Base-calling of sequencing data produced by high-throughput sequencing platforms is a fundamental process in current bioinformatics analysis. However, existing third-party probabilistic or machine-learning methods that significantly improve the accuracy of base-calls on these platforms are impractical for production use due to their computational inefficiency.

RESULTS: We directly formulate base-calling as a blind deconvolution problem and implemented BlindCall as an efficient solver to this inverse problem. BlindCall produced base-calls at accuracy comparable to state-of-the-art probabilistic methods while processing data at rates 10 times faster in most cases. The computational complexity of BlindCall scales linearly with read length making it better suited for new long-read sequencing technologies.

JA - Bioinformatics VL - 30 CP - 9 M3 - 10.1093/bioinformatics/btu010 ER - TY - JOUR T1 - Complete genome sequence of the quality control strain Staphylococcus aureus subsp. aureus ATCC 25923 JF - Genome announcements Y1 - 2014 A1 - Treangen, Todd J A1 - Maybank, Rosslyn A A1 - Enke, Sana A1 - Friss, Mary Beth A1 - Diviak, Lynn F A1 - Karaolis, David KR A1 - Koren, Sergey A1 - Ondov, Brian A1 - Phillippy, Adam M A1 - Bergman, Nicholas H VL - 2 ER - TY - JOUR T1 - Computational methods for optical mapping JF - GigaScienceGigaScience Y1 - 2014 A1 - Mendelowitz, Lee A1 - Pop, Mihai AB - Optical mapping and newer genome mapping technologies based on nicking enzymes provide low resolution but long-range genomic information. The optical mapping technique has been successfully used for assessing the quality of genome assemblies and for detecting large-scale structural variants and rearrangements that cannot be detected using current paired end sequencing protocols. Here, we review several algorithms and methods for building consensus optical maps and aligning restriction patterns to a reference map, as well as methods for using optical maps with sequence assemblies. VL - 3 SN - 2047-217X U2 - 4323141 ER - TY - JOUR T1 - A computational study of the Warburg effect identifies metabolic targets inhibiting cancer migration. JF - Mol Syst Biol Y1 - 2014 A1 - Yizhak, Keren A1 - Le Dévédec, Sylvia E A1 - Rogkoti, Vasiliki Maria A1 - Baenke, Franziska A1 - de Boer, Vincent C A1 - Frezza, Christian A1 - Schulze, Almut A1 - van de Water, Bob A1 - Ruppin, Eytan AB -

Over the last decade, the field of cancer metabolism has mainly focused on studying the role of tumorigenic metabolic rewiring in supporting cancer proliferation. Here, we perform the first genome‐scale computational study of the metabolic underpinnings of cancer migration. We build genome‐scale metabolic models of the NCI‐60 cell lines that capture the Warburg effect (aerobic glycolysis) typically occurring in cancer cells. The extent of the Warburg effect in each of these cell line models is quantified by the ratio of glycolytic to oxidative ATP flux (AFR), which is found to be highly positively associated with cancer cell migration. We hence predicted that targeting genes that mitigate the Warburg effect by reducing the AFR may specifically inhibit cancer migration. By testing the anti‐migratory effects of silencing such 17 top predicted genes in four breast and lung cancer cell lines, we find that up to 13 of these novel predictions significantly attenuate cell migration either in all or one cell line only, while having almost no effect on cell proliferation. Furthermore, in accordance with the predictions, a significant reduction is observed in the ratio between experimentally measured ECAR and OCR levels following these perturbations. Inhibiting anti‐migratory targets is a promising future avenue in treating cancer since it may decrease cytotoxic‐related side effects that plague current anti‐proliferative treatments. Furthermore, it may reduce cytotoxic‐related clonal selection of more aggressive cancer cells and the likelihood of emerging resistance.

VL - 10 M3 - 10.15252/msb.20145746 ER - TY - Generic T1 - Conservation in first introns is positively associated with the number of exons within genes and the presence of regulatory epigenetic signals Y1 - 2014 A1 - Park, Seung A1 - Hannenhalli, Sridhar A1 - Choi, Sun JA - BMC Genomics VL - 15 UR - http://www.biomedcentral.com/1471-2164/15/526 CP - 1 J1 - BMC GenomicsBMC Genomics M3 - 10.1186/1471-2164-15-526 ER - TY - JOUR T1 - Construction of a dairy microbial genome catalog opens new perspectives for the metagenomic analysis of dairy fermented products JF - BMC GenomicsBMC Genomics Y1 - 2014 A1 - Almeida, Mathieu A1 - Hebert, Agnes A1 - Abraham, Anne-Laure A1 - Rasmussen, Simon A1 - Monnet, Christophe A1 - Pons, Nicolas A1 - Delbes, Celine A1 - Loux, Valentin A1 - Batto, Jean-Michel A1 - Leonard, Pierre A1 - Kennedy, Sean A1 - Ehrlich, Stanislas A1 - Pop, Mihai A1 - Montel, Marie-Christine A1 - Irlinger, Francoise A1 - Renault, Pierre AB - BACKGROUND:Microbial communities of traditional cheeses are complex and insufficiently characterized. The origin, safety and functional role in cheese making of these microbial communities are still not well understood. Metagenomic analysis of these communities by high throughput shotgun sequencing is a promising approach to characterize their genomic and functional profiles. Such analyses, however, critically depend on the availability of appropriate reference genome databases against which the sequencing reads can be aligned.RESULTS:We built a reference genome catalog suitable for short read metagenomic analysis using a low-cost sequencing strategy. We selected 142 bacteria isolated from dairy products belonging to 137 different species and 67 genera, and succeeded to reconstruct the draft genome of 117 of them at a standard or high quality level, including isolates from the genera Kluyvera, Luteococcus and Marinilactibacillus, still missing from public database. To demonstrate the potential of this catalog, we analysed the microbial composition of the surface of two smear cheeses and one blue-veined cheese, and showed that a significant part of the microbiota of these traditional cheeses was composed of microorganisms newly sequenced in our study.CONCLUSIONS:Our study provides data, which combined with publicly available genome references, represents the most expansive catalog to date of cheese-associated bacteria. Using this extended dairy catalog, we revealed the presence in traditional cheese of dominant microorganisms not deliberately inoculated, mainly Gram-negative genera such as Pseudoalteromonas haloplanktis or Psychrobacter immobilis, that may contribute to the characteristics of cheese produced through traditional methods. VL - 15 SN - 1471-2164 ER - TY - JOUR T1 - CTCF binding site sequence differences are associated with unique regulatory and functional trends during embryonic stem cell differentiation JF - Nucleic Acids ResNucleic Acids ResNucleic Acids Res Y1 - 2014 A1 - Plasschaert, R. N. A1 - Vigneau, S. A1 - Tempera, I. A1 - Gupta, R. A1 - Maksimoska, J. A1 - Everett, L. A1 - Davuluri, R. A1 - Mamorstein, R. A1 - Lieberman, P. M. A1 - Schultz, D. A1 - Sridhar Hannenhalli A1 - Bartolomei, M. S. KW - *Gene Expression Regulation KW - *Regulatory Elements, Transcriptional KW - Animals KW - Binding Sites KW - Cell Differentiation/*genetics KW - Cells, Cultured KW - Embryonic Stem Cells/cytology/*metabolism KW - Mice KW - Nucleotide Motifs KW - Protein Binding KW - Repressor Proteins/*metabolism AB - CTCF (CCCTC-binding factor) is a highly conserved multifunctional DNA-binding protein with thousands of binding sites genome-wide. Our previous work suggested that differences in CTCF's binding site sequence may affect the regulation of CTCF recruitment and its function. To investigate this possibility, we characterized changes in genome-wide CTCF binding and gene expression during differentiation of mouse embryonic stem cells. After separating CTCF sites into three classes (LowOc, MedOc and HighOc) based on similarity to the consensus motif, we found that developmentally regulated CTCF binding occurs preferentially at LowOc sites, which have lower similarity to the consensus. By measuring the affinity of CTCF for selected sites, we show that sites lost during differentiation are enriched in motifs associated with weaker CTCF binding in vitro. Specifically, enrichment for T at the 18(th) position of the CTCF binding site is associated with regulated binding in the LowOc class and can predictably reduce CTCF affinity for binding sites. Finally, by comparing changes in CTCF binding with changes in gene expression during differentiation, we show that LowOc and HighOc sites are associated with distinct regulatory functions. Our results suggest that the regulatory control of CTCF is dependent in part on specific motifs within its binding site. VL - 42 SN - 1362-4962 (Electronic)
0305-1048 (Linking) N1 - Plasschaert, Robert N
Vigneau, Sebastien
Tempera, Italo
Gupta, Ravi
Maksimoska, Jasna
Everett, Logan
Davuluri, Ramana
Mamorstein, Ronen
Lieberman, Paul M
Schultz, David
Hannenhalli, Sridhar
Bartolomei, Marisa S
eng
K99AI099153/AI/NIAID NIH HHS/
P30 CA10815/CA/NCI NIH HHS/
R01 CA140652/CA/NCI NIH HHS/
R01-GM052880/GM/NIGMS NIH HHS/
R01CA140652/CA/NCI NIH HHS/
R01GM085226/GM/NIGMS NIH HHS/
R01HD042026/HD/NICHD NIH HHS/
T32GM008216/GM/NIGMS NIH HHS/
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
England
2013/10/15 06:00
Nucleic Acids Res. 2014 Jan;42(2):774-89. doi: 10.1093/nar/gkt910. Epub 2013 Oct 10. U2 - 3902912 J1 - Nucleic acids researchNucleic acids research ER - TY - Generic T1 - Determinants of expression variability Y1 - 2014 A1 - Alemu, E. Y. A1 - Carl, J. W. A1 - Corrada Bravo, H. A1 - Hannenhalli, S. JA - Nucleic Acids Research VL - 42 UR - http://nar.oxfordjournals.org/lookup/doi/10.1093/nar/gkt1364 CP - 6 J1 - Nucleic Acids Research M3 - 10.1093/nar/gkt1364 ER - TY - Generic T1 - Developmental expression of chicken FOXN1 and putative target genes during feather development. Y1 - 2014 A1 - Darnell, Diana K A1 - Zhang, Li S A1 - Hannenhalli, Sridhar A1 - Yaklichkin, Sergey Y KW - Amino Acid Sequence KW - Animals KW - Biological Evolution KW - Blotting, Western KW - Cell Differentiation KW - Cells, Cultured KW - Chick Embryo KW - Chickens KW - Cloning, Molecular KW - Embryo, Nonmammalian KW - Epidermis KW - Feathers KW - Forkhead Transcription Factors KW - Gene Expression Regulation, Developmental KW - In Situ Hybridization KW - Molecular Sequence Data KW - Morphogenesis KW - Phylogeny KW - Real-Time Polymerase Chain Reaction KW - Reverse Transcriptase Polymerase Chain Reaction KW - RNA, Messenger KW - Sequence Homology, Amino Acid AB -

FOXN1 is a member of the forkhead box family of transcription factors. FOXN1 is crucial for hair outgrowth and thymus differentiation in mammals. Unlike the thymus, which is found in all amniotes, hair is an epidermal appendage that arose after the last shared common ancestor between mammals and birds, and hair and feathers differ markedly in their differentiation and gene expression. Here, we show that FOXN1 is expressed in embryonic chicken feathers, nails and thymus, demonstrating an evolutionary conservation that goes beyond obvious homology. At embryonic day (ED) 12, FOXN1 is expressed in some feather buds and at ED13 expression extends along the length of the feather filament. At ED14 FOXN1 mRNA is restricted to the proximal feather filament and is not detectable in distal feather shafts. At the base of the feather, FOXN1 is expressed in the epithelium of the feather sheath and distal barb and marginal plate, whereas in the midsection FOXN1 transcripts are mainly detected in the barb plates of the feather filament. FOXN1 is also expressed in claws; however, no expression was detected in skin or scales. Despite expression of FOXN1 in developing feathers, examination of chick homologs of five putative mammalian FOXN1 target genes shows that, while these genes are expressed in feathers, there is little similarity to the FOXN1 expression pattern, suggesting that some gene regulatory networks may have diverged during evolution of epidermal appendages.

JA - Int J Dev Biol VL - 58 CP - 1 M3 - 10.1387/ijdb.130023sy ER - TY - Generic T1 - Diarrhea in young children from low-income countries leads to large-scale alterations in intestinal microbiota composition. Y1 - 2014 A1 - Pop, Mihai A1 - Walker, Alan W A1 - Paulson, Joseph A1 - Lindsay, Brianna A1 - Antonio, Martin A1 - Hossain, M Anowar A1 - Oundo, Joseph A1 - Tamboura, Boubou A1 - Mai, Volker A1 - Astrovskaya, Irina A1 - Corrada Bravo, Hector A1 - Rance, Richard A1 - Stares, Mark A1 - Levine, Myron M A1 - Panchalingam, Sandra A1 - Kotloff, Karen A1 - Ikumapayi, Usman N A1 - Ebruke, Chinelo A1 - Adeyemi, Mitchell A1 - Ahmed, Dilruba A1 - Ahmed, Firoz A1 - Alam, Meer Taifur A1 - Amin, Ruhul A1 - Siddiqui, Sabbir A1 - Ochieng, John B A1 - Ouma, Emmanuel A1 - Juma, Jane A1 - Mailu, Euince A1 - Omore, Richard A1 - Morris, J Glenn A1 - Breiman, Robert F A1 - Saha, Debasish A1 - Parkhill, Julian A1 - Nataro, James P A1 - Stine, O Colin KW - Bangladesh KW - Base Sequence KW - Case-Control Studies KW - Child, Preschool KW - Diarrhea, Infantile KW - Dysentery KW - Feces KW - Female KW - Gambia KW - HUMANS KW - Infant KW - Infant, Newborn KW - Intestines KW - Kenya KW - Male KW - Mali KW - Microbiota KW - Molecular Typing KW - Poverty KW - RNA, Bacterial KW - RNA, Ribosomal, 16S AB -

BACKGROUND: Diarrheal diseases continue to contribute significantly to morbidity and mortality in infants and young children in developing countries. There is an urgent need to better understand the contributions of novel, potentially uncultured, diarrheal pathogens to severe diarrheal disease, as well as distortions in normal gut microbiota composition that might facilitate severe disease.

RESULTS: We use high throughput 16S rRNA gene sequencing to compare fecal microbiota composition in children under five years of age who have been diagnosed with moderate to severe diarrhea (MSD) with the microbiota from diarrhea-free controls. Our study includes 992 children from four low-income countries in West and East Africa, and Southeast Asia. Known pathogens, as well as bacteria currently not considered as important diarrhea-causing pathogens, are positively associated with MSD, and these include Escherichia/Shigella, and Granulicatella species, and Streptococcus mitis/pneumoniae groups. In both cases and controls, there tend to be distinct negative correlations between facultative anaerobic lineages and obligate anaerobic lineages. Overall genus-level microbiota composition exhibit a shift in controls from low to high levels of Prevotella and in MSD cases from high to low levels of Escherichia/Shigella in younger versus older children; however, there was significant variation among many genera by both site and age.

CONCLUSIONS: Our findings expand the current understanding of microbiota-associated diarrhea pathogenicity in young children from developing countries. Our findings are necessarily based on correlative analyses and must be further validated through epidemiological and molecular techniques.

JA - Genome Biol VL - 15 CP - 6 M3 - 10.1186/gb-2014-15-6-r76 ER - TY - Generic T1 - Epiviz: interactive visual analytics for functional genomics data. Y1 - 2014 A1 - Chelaru, Florin A1 - Smith, Llewellyn A1 - Goldstein, Naomi A1 - Bravo, Héctor Corrada KW - algorithms KW - Chromosome mapping KW - Data Mining KW - database management systems KW - Databases, Genetic KW - Genomics KW - Internet KW - software KW - User-Computer Interface AB -

Visualization is an integral aspect of genomics data analysis. Algorithmic-statistical analysis and interactive visualization are most effective when used iteratively. Epiviz (http://epiviz.cbcb.umd.edu/), a web-based genome browser, and the Epivizr Bioconductor package allow interactive, extensible and reproducible visualization within a state-of-the-art data-analysis platform.

JA - Nat Methods VL - 11 CP - 9 M3 - 10.1038/nmeth.3038 ER - TY - Generic T1 - An evaluation of Monte-Carlo logic and logicFS motivated by a study of the regulation of gene expression in heart failure Y1 - 2014 A1 - Lu, Yun A1 - Hannenhalli, Sridhar A1 - Cappola, Tom A1 - Putt, Mary JA - Journal of Applied Statistics VL - 41 UR - http://www.tandfonline.com/doi/abs/10.1080/02664763.2014.898133 CP - 9 J1 - Journal of Applied Statistics M3 - 10.1080/02664763.2014.898133 ER - TY - JOUR T1 - A Gateway for Phylogenetic Analysis Powered by Grid Computing Featuring GARLI 2.0 JF - Syst Biol Y1 - 2014 A1 - Adam L. Bazinet A1 - Zwickl, Derrick J. A1 - Michael P. Cummings AB -

We introduce molecularevolution.org, a publicly available gateway for high-throughput, maximum likelihood phylogenetic analysis powered by grid computing. The gateway features a garli 2.0 web service that enables a user to quickly and easily submit thousands of maximum likelihood tree searches or bootstrap searches that are executed in parallel on distributed computing resources. The garli web service allows one to easily specify partitioned substitution models using a graphical interface, and it performs sophisticated post-processing of phylogenetic results. Although the garli web service has been used by the research community for over three years, here we formally announce the availability of the service, describe its capabilities, highlight new features and recent improvements, and provide details about how the grid system efficiently delivers high-quality phylogenetic results.

ER - TY - Generic T1 - Glycan Degradation (GlyDeR) Analysis Predicts Mammalian Gut Microbiota Abundance and Host Diet-Specific Adaptations Y1 - 2014 A1 - Eilam, O. A1 - Zarecki, R. A1 - Oberhardt, M. A1 - Ursell, L. K. A1 - Kupiec, M. A1 - Knight, R. A1 - Gophna, U. A1 - Ruppin, E. JA - mBio VL - 5 UR - http://mbio.asm.org/cgi/doi/10.1128/mBio.01526-14 CP - 4 J1 - mBio M3 - 10.1128/mBio.01526-14 ER - TY - JOUR T1 - The Harvest suite for rapid core-genome alignment and visualization of thousands of intraspecific microbial genomes JF - Genome biology Y1 - 2014 A1 - Todd Treangen A1 - Ondov, Brian D A1 - Koren, Sergey A1 - Phillippy, Adam M VL - 15 ER - TY - Generic T1 - Integrating Transcriptomics with Metabolic Modeling Predicts Biomarkers and Drug Targets for Alzheimer's Disease Y1 - 2014 A1 - Stempler, Shiri A1 - Yizhak, Keren A1 - Ruppin, Eytan ED - Fong, Stephen S. JA - PLoS ONE VL - 9 UR - http://www.cs.tau.ac.il/~ruppin/ad_plos1.pdf CP - 8 J1 - PLoS ONE M3 - 10.1371/journal.pone.0105383 ER - TY - Generic T1 - Large hypomethylated blocks as a universal defining epigenetic alteration in human solid tumors. Y1 - 2014 A1 - Timp, Winston A1 - Bravo, Héctor Corrada A1 - McDonald, Oliver G A1 - Goggins, Michael A1 - Umbricht, Chris A1 - Zeiger, Martha A1 - Feinberg, Andrew P A1 - Irizarry, Rafael A AB -

BACKGROUND: One of the most provocative recent observations in cancer epigenetics is the discovery of large hypomethylated blocks, including single copy genes, in colorectal cancer, that correspond in location to heterochromatic LOCKs (large organized chromatin lysine-modifications) and LADs (lamin-associated domains).

METHODS: Here we performed a comprehensive genome-scale analysis of 10 breast, 28 colon, nine lung, 38 thyroid, 18 pancreas cancers, and five pancreas neuroendocrine tumors as well as matched normal tissue from most of these cases, as well as 51 premalignant lesions. We used a new statistical approach that allows the identification of large hypomethylated blocks on the Illumina HumanMethylation450 BeadChip platform.

RESULTS: We find that hypomethylated blocks are a universal feature of common solid human cancer, and that they occur at the earliest stage of premalignant tumors and progress through clinical stages of thyroid and colon cancer development. We also find that the disrupted CpG islands widely reported previously, including hypermethylated island bodies and hypomethylated shores, are enriched in hypomethylated blocks, with flattening of the methylation signal within and flanking the islands. Finally, we found that genes showing higher between individual gene expression variability are enriched within these hypomethylated blocks.

CONCLUSION: Thus hypomethylated blocks appear to be a universal defining epigenetic alteration in human cancer, at least for common solid tumors.

JA - Genome Med VL - 6 CP - 8 M3 - 10.1186/s13073-014-0061-y ER - TY - Generic T1 - Maximal Sum of Metabolic Exchange Fluxes Outperforms Biomass Yield as a Predictor of Growth Rate of Microorganisms Y1 - 2014 A1 - Zarecki, Raphy A1 - Oberhardt, Matthew A. A1 - Yizhak, Keren A1 - Wagner, Allon A1 - Shtifman Segal, Ella A1 - Freilich, Shiri A1 - Henry, Christopher S. A1 - Gophna, Uri A1 - Ruppin, Eytan ED - Fong, Stephen S. JA - PLoS ONE VL - 9 UR - http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0098372 CP - 5 J1 - PLoS ONE M3 - 10.1371/journal.pone.0098372 ER - TY - Generic T1 - Minfi: a flexible and comprehensive Bioconductor package for the analysis of Infinium DNA methylation microarrays. Y1 - 2014 A1 - Aryee, Martin J A1 - Jaffe, Andrew E A1 - Corrada-Bravo, Hector A1 - Ladd-Acosta, Christine A1 - Feinberg, Andrew P A1 - Hansen, Kasper D A1 - Irizarry, Rafael A KW - Aged KW - algorithms KW - Colonic Neoplasms KW - DNA Methylation KW - Genome KW - High-Throughput Nucleotide Sequencing KW - HUMANS KW - Oligonucleotide Array Sequence Analysis KW - Polymorphism, Single Nucleotide KW - software AB -

MOTIVATION: The recently released Infinium HumanMethylation450 array (the '450k' array) provides a high-throughput assay to quantify DNA methylation (DNAm) at ∼450 000 loci across a range of genomic features. Although less comprehensive than high-throughput sequencing-based techniques, this product is more cost-effective and promises to be the most widely used DNAm high-throughput measurement technology over the next several years.

RESULTS: Here we describe a suite of computational tools that incorporate state-of-the-art statistical techniques for the analysis of DNAm data. The software is structured to easily adapt to future versions of the technology. We include methods for preprocessing, quality assessment and detection of differentially methylated regions from the kilobase to the megabase scale. We show how our software provides a powerful and flexible development platform for future methods. We also illustrate how our methods empower the technology to make discoveries previously thought to be possible only with sequencing-based methods.

AVAILABILITY AND IMPLEMENTATION: http://bioconductor.org/packages/release/bioc/html/minfi.html.

CONTACT: khansen@jhsph.edu; rafa@jimmy.harvard.edu

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

JA - Bioinformatics VL - 30 CP - 10 M3 - 10.1093/bioinformatics/btu049 ER - TY - JOUR T1 - A molecular phylogeny and revised classification for the oldest ditrysian moth lineages (Lepidoptera: Tineoidea), with implications for ancestral feeding habits of the mega-diverse Ditrysia JF - Systematic Entomology Y1 - 2014 A1 - Regier, Jerome C A1 - Mitter, Charles A1 - Davis, Donald R. A1 - HARRISON, TERRY L. A1 - Sohn, Jae-Cheon A1 - Michael P. Cummings A1 - Zwick, Andreas A1 - Mitter, Kim T. VL - 40 M3 - 10.1111/syen.12110 ER - TY - Generic T1 - Network-level architecture and the evolutionary potential of underground metabolism Y1 - 2014 A1 - Notebaart, R. A. A1 - Szappanos, B. A1 - Kintses, B. A1 - Pal, F. A1 - Gyorkei, A. A1 - Bogos, B. A1 - Lazar, V. A1 - Spohn, R. A1 - Bogos, B. A1 - Wagner, A. A1 - Ruppin, E. A1 - Pal, C. A1 - Papp, B. JA - Proceedings of the National Academy of Sciences VL - 111 UR - http://www.pnas.org/cgi/doi/10.1073/pnas.1406102111 CP - 32 J1 - Proceedings of the National Academy of Sciences M3 - 10.1073/pnas.1406102111 ER - TY - JOUR T1 - A new rhesus macaque assembly and annotation for next-generation sequencing analyses JF - Biology direct Y1 - 2014 A1 - Zimin, Aleksey V A1 - Cornish, Adam S A1 - Maudhoo, Mnirnal D A1 - Gibbs, Robert M A1 - Zhang, Xiongfei A1 - Pandey, Sanjit A1 - Meehan, Daniel T A1 - Wipfler, Kristin A1 - Bosinger, Steven E A1 - Johnson, Zachary P A1 - Todd Treangen VL - 9 ER - TY - JOUR T1 - A Novel Nutritional Predictor Links Microbial Fastidiousness with Lowered Ubiquity, Growth Rate, and Cooperativeness JF - PLoS Computational Biology Y1 - 2014 A1 - Zarecki, Raphy A1 - Oberhardt, Matthew A. A1 - Reshef, Leah A1 - Gophna, Uri A1 - Ruppin, Eytan ED - Maranas, Costas D. VL - 10 UR - http://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1003726 CP - 7 J1 - PLoS Comput Biol M3 - 10.1371/journal.pcbi.1003726 ER - TY - JOUR T1 - Phenotype-based cell-specific metabolic modeling reveals metabolic liabilities of cancer. JF - Elife Y1 - 2014 A1 - Yizhak, Keren A1 - Gaude, Edoardo A1 - Le Dévédec, Sylvia A1 - Waldman, Yedael Y A1 - Stein, Gideon Y A1 - van de Water, Bob A1 - Frezza, Christian A1 - Ruppin, Eytan KW - algorithms KW - Antineoplastic Agents KW - Biomarkers, Tumor KW - Carboxy-Lyases KW - Cell Line, Tumor KW - Cell Proliferation KW - Citric Acid Cycle KW - Fatty Acids KW - Gene Knockdown Techniques KW - Genome, Human KW - HUMANS KW - Lymphocytes KW - Models, Biological KW - Neoplasms KW - Oxidation-Reduction KW - PHENOTYPE KW - Precision Medicine AB -

Utilizing molecular data to derive functional physiological models tailored for specific cancer cells can facilitate the use of individually tailored therapies. To this end we present an approach termed PRIME for generating cell-specific genome-scale metabolic models (GSMMs) based on molecular and phenotypic data. We build >280 models of normal and cancer cell-lines that successfully predict metabolic phenotypes in an individual manner. We utilize this set of cell-specific models to predict drug targets that selectively inhibit cancerous but not normal cell proliferation. The top predicted target, MLYCD, is experimentally validated and the metabolic effects of MLYCD depletion investigated. Furthermore, we tested cell-specific predicted responses to the inhibition of metabolic enzymes, and successfully inferred the prognosis of cancer patients based on their PRIME-derived individual GSMMs. These results lay a computational basis and a counterpart experimental proof of concept for future personalized metabolic modeling applications, enhancing the search for novel selective anticancer therapies.

VL - 3 M3 - 10.7554/eLife.03641 ER - TY - JOUR T1 - Predicting cancer-specific vulnerability via data-driven detection of synthetic lethality. JF - Cell Y1 - 2014 A1 - Jerby-Arnon, Livnat A1 - Pfetzer, Nadja A1 - Waldman, Yedael Y A1 - McGarry, Lynn A1 - James, Daniel A1 - Shanks, Emma A1 - Seashore-Ludlow, Brinton A1 - Weinstock, Adam A1 - Geiger, Tamar A1 - Clemons, Paul A A1 - Gottlieb, Eyal A1 - Ruppin, Eytan KW - Breast Neoplasms KW - Cell Line, Tumor KW - Computational Biology KW - Data Mining KW - Genes, Tumor Suppressor KW - HUMANS KW - Neoplasms KW - Oncogenes KW - RNA, Small Interfering KW - workflow AB -

Synthetic lethality occurs when the inhibition of two genes is lethal while the inhibition of each single gene is not. It can be harnessed to selectively treat cancer by identifying inactive genes in a given cancer and targeting their synthetic lethal (SL) partners. We present a data-driven computational pipeline for the genome-wide identification of SL interactions in cancer by analyzing large volumes of cancer genomic data. First, we show that the approach successfully captures known SL partners of tumor suppressors and oncogenes. We then validate SL predictions obtained for the tumor suppressor VHL. Next, we construct a genome-wide network of SL interactions in cancer and demonstrate its value in predicting gene essentiality and clinical prognosis. Finally, we identify synthetic lethality arising from gene overactivation and use it to predict drug efficacy. These results form a computational basis for exploiting synthetic lethality to uncover cancer-specific susceptibilities.

VL - 158 CP - 5 M3 - 10.1016/j.cell.2014.07.027 ER - TY - JOUR T1 - Quantitative 4D analyses of epithelial folding during Drosophila gastrulation. JF - Development Y1 - 2014 A1 - Khan, Zia A1 - Wang, Yu-Chiun A1 - Wieschaus, Eric F A1 - Kaschube, Matthias KW - Animals KW - Body Patterning KW - Cell Shape KW - Cell Tracking KW - Drosophila melanogaster KW - Epithelial Cells KW - Epithelium KW - Gastrulation KW - Image Processing, Computer-Assisted KW - software AB -

Understanding the cellular and mechanical processes that underlie the shape changes of individual cells and their collective behaviors in a tissue during dynamic and complex morphogenetic events is currently one of the major frontiers in developmental biology. The advent of high-speed time-lapse microscopy and its use in monitoring the cellular events in fluorescently labeled developing organisms demonstrate tremendous promise in establishing detailed descriptions of these events and could potentially provide a foundation for subsequent hypothesis-driven research strategies. However, obtaining quantitative measurements of dynamic shapes and behaviors of cells and tissues in a rapidly developing metazoan embryo using time-lapse 3D microscopy remains technically challenging, with the main hurdle being the shortage of robust imaging processing and analysis tools. We have developed EDGE4D, a software tool for segmenting and tracking membrane-labeled cells using multi-photon microscopy data. Our results demonstrate that EDGE4D enables quantification of the dynamics of cell shape changes, cell interfaces and neighbor relations at single-cell resolution during a complex epithelial folding event in the early Drosophila embryo. We expect this tool to be broadly useful for the analysis of epithelial cell geometries and movements in a wide variety of developmental contexts.

VL - 141 CP - 14 M3 - 10.1242/dev.107730 ER - TY - Generic T1 - Removing batch effects for prediction problems with frozen surrogate variable analysis. Y1 - 2014 A1 - Parker, Hilary S A1 - Corrada Bravo, Hector A1 - Leek, Jeffrey T AB -

Batch effects are responsible for the failure of promising genomic prognostic signatures, major ambiguities in published genomic results, and retractions of widely-publicized findings. Batch effect corrections have been developed to remove these artifacts, but they are designed to be used in population studies. But genomic technologies are beginning to be used in clinical applications where samples are analyzed one at a time for diagnostic, prognostic, and predictive applications. There are currently no batch correction methods that have been developed specifically for prediction. In this paper, we propose an new method called frozen surrogate variable analysis (fSVA) that borrows strength from a training set for individual sample batch correction. We show that fSVA improves prediction accuracy in simulations and in public genomic studies. fSVA is available as part of the sva Bioconductor package.

JA - PeerJ VL - 2 M3 - 10.7717/peerj.561 ER - TY - JOUR T1 - Reply to: "A fair comparison" JF - Nature Methods Y1 - 2014 A1 - Paulson, Joseph N A1 - Bravo, éctor Corrada A1 - Pop, Mihai VL - 11 UR - http://www.nature.com/doifinder/10.1038/nmeth.2898 CP - 4 J1 - Nat Meth M3 - 10.1038/nmeth.2898 ER - TY - Generic T1 - RNA-sequencing of the brain transcriptome implicates dysregulation of neuroplasticity, circadian rhythms and GTPase binding in bipolar disorder. Y1 - 2014 A1 - Akula, N A1 - Barb, J A1 - Jiang, X A1 - Wendland, J R A1 - Choi, K H A1 - Sen, S K A1 - Hou, L A1 - Chen, D T W A1 - Laje, G A1 - Johnson, K A1 - Lipska, B K A1 - Kleinman, J E A1 - Corrada-Bravo, H A1 - Detera-Wadleigh, S A1 - Munson, P J A1 - McMahon, F J KW - Adult KW - Aged KW - Bipolar Disorder KW - Circadian Rhythm KW - Female KW - Genome-Wide Association Study KW - GTP Phosphohydrolases KW - HUMANS KW - Male KW - Meta-Analysis as Topic KW - Microarray Analysis KW - Middle Aged KW - Neuronal Plasticity KW - Polymerase Chain Reaction KW - Prefrontal Cortex KW - Principal Component Analysis KW - Sequence Analysis, RNA KW - Transcriptome KW - Young Adult AB -

RNA-sequencing (RNA-seq) is a powerful technique to investigate the complexity of gene expression in the human brain. We used RNA-seq to survey the brain transcriptome in high-quality postmortem dorsolateral prefrontal cortex from 11 individuals diagnosed with bipolar disorder (BD) and from 11 age- and gender-matched controls. Deep sequencing was performed, with over 350 million reads per specimen. At a false discovery rate of <5%, we detected five differentially expressed (DE) genes and 12 DE transcripts, most of which have not been previously implicated in BD. Among these, Prominin 1/CD133 and ATP-binding cassette-sub-family G-member2 (ABCG2) have important roles in neuroplasticity. We also show for the first time differential expression of long noncoding RNAs (lncRNAs) in BD. DE transcripts include those of serine/arginine-rich splicing factor 5 (SRSF5) and regulatory factor X4 (RFX4), which along with lncRNAs have a role in mammalian circadian rhythms. The DE genes were significantly enriched for several Gene Ontology categories. Of these, genes involved with GTPase binding were also enriched for BD-associated SNPs from previous genome-wide association studies, suggesting that differential expression of these genes is not simply a consequence of BD or its treatment. Many of these findings were replicated by microarray in an independent sample of 60 cases and controls. These results highlight common pathways for inherited and non-inherited influences on disease risk that may constitute good targets for novel therapies.

JA - Mol Psychiatry VL - 19 CP - 11 M3 - 10.1038/mp.2013.170 ER - TY - JOUR T1 - RNA-sequencing of the brain transcriptome implicates dysregulation of neuroplasticity, circadian rhythms and GTPase binding in bipolar disorder JF - Molecular psychiatry Y1 - 2014 A1 - Akula, N. A1 - Barb, J. A1 - Jiang, X. A1 - Wendland, J. R. A1 - Choi, K. H. A1 - Sen, S. K. A1 - Hou, L. A1 - Chen, D. T. W. A1 - Laje, G. A1 - Johnson, K. A1 - Lipska, B. K. A1 - Kleinman, J. E. A1 - Héctor Corrada Bravo A1 - Detera-Wadleigh, S. A1 - Munson, P. J. A1 - McMahon, F. J. AB - RNA-sequencing (RNA-seq) is a powerful technique to investigate the complexity of gene expression in the human brain. We used RNA-seq to survey the brain transcriptome in high-quality postmortem dorsolateral prefrontal cortex from 11 individuals diagnosed with bipolar disorder (BD) and from 11 age- and gender-matched controls. Deep sequencing was performed, with over 350 million reads per specimen. At a false discovery rate of <5%, we detected five differentially expressed (DE) genes and 12 DE transcripts, most of which have not been previously implicated in BD. Among these, Prominin 1/CD133 and ATP-binding cassette-sub-family G-member2 (ABCG2) have important roles in neuroplasticity. We also show for the first time differential expression of long noncoding RNAs (lncRNAs) in BD. DE transcripts include those of serine/arginine-rich splicing factor 5 (SRSF5) and regulatory factor X4 (RFX4), which along with lncRNAs have a role in mammalian circadian rhythms. The DE genes were significantly enriched for several Gene Ontology categories. Of these, genes involved with GTPase binding were also enriched for BD-associated SNPs from previous genome-wide association studies, suggesting that differential expression of these genes is not simply a consequence of BD or its treatment. Many of these findings were replicated by microarray in an independent sample of 60 cases and controls. These results highlight common pathways for inherited and non-inherited influences on disease risk that may constitute good targets for novel therapies.Molecular Psychiatry advance online publication, 7 January 2014; doi:10.1038/mp.2013.170. N1 - http://www.ncbi.nlm.nih.gov/pubmed/24393808?dopt=Abstract ER - TY - Generic T1 - Sailfish enables alignment-free isoform quantification from RNA-seq reads using lightweight algorithms. Y1 - 2014 A1 - Patro, Rob A1 - Mount, Stephen M A1 - Kingsford, Carl KW - algorithms KW - Brain Chemistry KW - Computational Biology KW - HUMANS KW - Models, Biological KW - RNA Isoforms KW - Sequence Analysis, RNA KW - software AB -

We introduce Sailfish, a computational method for quantifying the abundance of previously annotated RNA isoforms from RNA-seq data. Because Sailfish entirely avoids mapping reads, a time-consuming step in all current methods, it provides quantification estimates much faster than do existing approaches (typically 20 times faster) without loss of accuracy. By facilitating frequent reanalysis of data and reducing the need to optimize parameters, Sailfish exemplifies the potential of lightweight algorithms for efficiently processing sequencing reads.

JA - Nat Biotechnol VL - 32 CP - 5 M3 - 10.1038/nbt.2862 ER - TY - JOUR T1 - Stable isotope labeling of phosphoproteins for large-scale phosphorylation rate determination. JF - Mol Cell Proteomics Y1 - 2014 A1 - Molden, Rosalynn C A1 - Goya, Jonathan A1 - Khan, Zia A1 - Garcia, Benjamin A KW - cell cycle KW - HEK293 Cells KW - HeLa Cells KW - HUMANS KW - Isotope Labeling KW - Kinetics KW - Peptide Mapping KW - Phosphoproteins KW - Phosphorylation KW - proteomics KW - Tandem Mass Spectrometry AB -

Signals that control responses to stimuli and cellular function are transmitted through the dynamic phosphorylation of thousands of proteins by protein kinases. Many techniques have been developed to study phosphorylation dynamics, including several mass spectrometry (MS)-based methods. Over the past few decades, substantial developments have been made in MS techniques for the large-scale identification of proteins and their post-translational modifications. Nevertheless, all of the current MS-based techniques for quantifying protein phosphorylation dynamics rely on the measurement of changes in peptide abundance levels, and many methods suffer from low confidence in phosphopeptide identification due to poor fragmentation. Here we have optimized an approach for the stable isotope labeling of amino acids by phosphate using [γ-¹⁸O₄]ATP in nucleo to determine global site-specific phosphorylation rates. The advantages of this metabolic labeling technique are increased confidence in phosphorylated peptide identification, direct labeling of phosphorylation sites, measurement phosphorylation rates, and the identification of actively phosphorylated sites in a cell-like environment. In this study we calculated approximate rate constants for over 1,000 phosphorylation sites based on labeling progress curves. We measured a wide range of phosphorylation rate constants from 0.34 min⁻¹ to 0.001 min⁻¹. Finally, we applied stable isotope labeling of amino acids by phosphate to identify sites that have different phosphorylation kinetics during G1/S and M phase. We found that most sites had very similar phosphorylation rates under both conditions; however, a small subset of sites on proteins involved in the mitotic spindle were more actively phosphorylated during M phase, whereas proteins involved in DNA replication and transcription were more actively phosphorylated during G1/S phase. The data have been deposited to the ProteomeXchange with the identifier PXD000680.

VL - 13 CP - 4 M3 - 10.1074/mcp.O113.036145 ER - TY - JOUR T1 - Stoichiometry of site-specific lysine acetylation in an entire proteome. JF - J Biol Chem Y1 - 2014 A1 - Baeza, Josue A1 - Dowell, James A A1 - Smallegan, Michael J A1 - Fan, Jing A1 - Amador-Noguez, Daniel A1 - Khan, Zia A1 - Denu, John M KW - Acetylation KW - Amino Acid Sequence KW - Bacterial Proteins KW - Chromatography, High Pressure Liquid KW - Computational Biology KW - Escherichia coli KW - Lysine KW - Molecular Sequence Data KW - Proteome KW - Tandem Mass Spectrometry AB -

Acetylation of lysine ϵ-amino groups influences many cellular processes and has been mapped to thousands of sites across many organisms. Stoichiometric information of acetylation is essential to accurately interpret biological significance. Here, we developed and employed a novel method for directly quantifying stoichiometry of site-specific acetylation in the entire proteome of Escherichia coli. By coupling isotopic labeling and a novel pairing algorithm, our approach performs an in silico enrichment of acetyl peptides, circumventing the need for immunoenrichment. We investigated the function of the sole NAD(+)-dependent protein deacetylase, CobB, on both site-specific and global acetylation. We quantified 2206 peptides from 899 proteins and observed a wide distribution of acetyl stoichiometry, ranging from less than 1% up to 98%. Bioinformatic analysis revealed that metabolic enzymes, which either utilize or generate acetyl-CoA, and proteins involved in transcriptional and translational processes displayed the highest degree of acetylation. Loss of CobB led to increased global acetylation at low stoichiometry sites and induced site-specific changes at high stoichiometry sites, and biochemical analysis revealed altered acetyl-CoA metabolism. Thus, this study demonstrates that sirtuin deacetylase deficiency leads to both site-specific and global changes in protein acetylation stoichiometry, affecting central metabolism.

VL - 289 CP - 31 M3 - 10.1074/jbc.M114.581843 ER - TY - JOUR T1 - TIPP:Taxonomic Identification and Phylogenetic Profiling JF - BioinformaticsBioinformatics Y1 - 2014 A1 - Nguyen, Nam-phuong A1 - Mirarab, Siavash A1 - Liu, Bo A1 - Pop, Mihai A1 - Warnow, Tandy AB - Motivation: Abundance profiling (also called “phylogenetic profiling”) is a crucial step in understanding the diversity of a metagenomic sample, and one of the basic techniques used for this is taxonomic identification of the metagenomic reads.Results: We present TIPP (taxon identification and phylogenetic profiling), a new marker-based taxon identification and abundance profiling method. TIPP combines SEPP, a phylogenetic placement method, with statistical techniques to control the classification precision and recall, and results in improved abundance profiles. TIPP is highly accurate even in the presence of high indel errors and novel genomes, and matches or improves on previous approaches, including NBC, mOTU, PhymmBL, MetaPhyler, and MetaPhlAn.Availability: Software and supplementary materials are available at http://www.cs.utexas.edu/users/phylo/software/sepp/tipp-submission/.Contact: warnow@illinois.edu ER - TY - CHAP T1 - AWTY, BAMBE, BEAGLE, BEAST, BEAUti, Bio++, DataMonkey, DendroPy, DnaSP, ENCprime/SeqCount, FigTree, GARLI, genealogical sorting index (gsi), HyPhy, IMa2, jModelTest, JELLYFISH, LAMARC, MacClade, MEGA, Mesquite T2 - Dictionary of Bioinformatics Y1 - 2013 A1 - Michael P. Cummings ED - Hancock, J. ED - Zvelebil, M. JA - Dictionary of Bioinformatics PB - Wiley-Liss CY - Hoboken ER - TY - JOUR T1 - Can RNA-Seq resolve the rapid radiation of advanced moths and butterflies (Hexapoda: Lepidoptera: Apoditrysia)? An exploratory study JF - PLoS One Y1 - 2013 A1 - Adam L. Bazinet A1 - Michael P. Cummings A1 - Mitter, Kim T. A1 - Mitter, Charles W. AB -

Recent molecular phylogenetic studies of the insect order Lepidoptera have robustly resolved family-level divergences within most superfamilies, and most divergences among the relatively species-poor early-arising superfamilies. In sharp contrast, relationships among the superfamilies of more advanced moths and butterflies that comprise the mega-diverse clade Apoditrysia (ca. 145,000 spp.) remain mostly poorly supported. This uncertainty, in turn, limits our ability to discern the origins, ages and evolutionary consequences of traits hypothesized to promote the spectacular diversification of Apoditrysia. Low support along the apoditrysian "backbone" probably reflects rapid diversification. If so, it may be feasible to strengthen resolution by radically increasing the gene sample, but case studies have been few. We explored the potential of next-generation sequencing to conclusively resolve apoditrysian relationships. We used transcriptome RNA-Seq to generate 1579 putatively orthologous gene sequences across a broad sample of 40 apoditrysians plus four outgroups, to which we added two taxa from previously published data. Phylogenetic analysis of a 46-taxon, 741-gene matrix, resulting from a strict filter that eliminated ortholog groups containing any apparent paralogs, yielded dramatic overall increase in bootstrap support for deeper nodes within Apoditrysia as compared to results from previous and concurrent 19-gene analyses. High support was restricted mainly to the huge subclade Obtectomera broadly defined, in which 11 of 12 nodes subtending multiple superfamilies had bootstrap support of 100%. The strongly supported nodes showed little conflict with groupings from previous studies, and were little affected by changes in taxon sampling, suggesting that they reflect true signal rather than artifacts of massive gene sampling. In contrast, strong support was seen at only 2 of 11 deeper nodes among the "lower", non-obtectomeran apoditrysians. These represent a much harder phylogenetic problem, for which one path to resolution might include further increase in gene sampling, together with improved orthology assignments.

VL - 8 ER - TY - JOUR T1 - Contribution of nucleosome binding preferences and co-occurring DNA sequences to transcription factor binding JF - BMC Genomics Y1 - 2013 A1 - He, Ximiao A1 - Chatterjee, Raghunath A1 - John, Sam A1 - Bravo, Hector A1 - Sathyanarayana, B K A1 - Biddie, Simon C A1 - FitzGerald, Peter C A1 - Stamatoyannopoulos, John A A1 - Hager, Gordon L A1 - Vinson, Charles VL - 14 UR - http://bmcgenomics.biomedcentral.com/articles/10.1186/1471-2164-14-428 CP - 1 J1 - BMC GenomicsBMC Genomics M3 - 10.1186/1471-2164-14-428 ER - TY - Generic T1 - Correlated evolution of positions within mammalian cis elements Y1 - 2013 A1 - R. Mukherjee A1 - L. N. S. Singh A1 - Evans, P. A1 - Sridhar Hannenhalli JA - Plos One VL - 8 ER - TY - JOUR T1 - De novo likelihood-based measures for comparing genome assemblies JF - BMC research notes Y1 - 2013 A1 - Ghodsi, Mohammadreza A1 - Christopher M. Hill A1 - Irina Astrovskaya A1 - Lin, Henry A1 - Sommer, Dan D. A1 - Koren, Sergey A1 - M. Pop PB - BioMed Central Ltd VL - 6 ER - TY - CONF T1 - De novo likelihood-based measures for comparing metagenomic assemblies T2 - 2013 IEEE International Conference on Bioinformatics and Biomedicine (BIBM) Y1 - 2013 A1 - Hill, Christopher M A1 - Irina Astrovskaya A1 - Huang, Howard A1 - Koren, Sergey A1 - Memon, Atif A1 - Todd Treangen A1 - Pop, Mihai JA - 2013 IEEE International Conference on Bioinformatics and Biomedicine (BIBM) PB - IEEE CY - Shanghai, China ER - TY - JOUR T1 - A decision-theory approach to interpretable set analysis for high-dimensional data JF - BiometricsBiometrics Y1 - 2013 A1 - Boca, Simina M. A1 - Héctor Corrada Bravo A1 - Caffo, Brian A1 - Leek, Jeffrey T. A1 - Parmigiani, Giovanni AB - A key problem in high-dimensional significance analysis is to find pre-defined sets that show enrichment for a statistical signal of interest; the classic example is the enrichment of gene sets for differentially expressed genes. Here, we propose a new decision-theory approach to the analysis of gene sets which focuses on estimating the fraction of non-null variables in a set. We introduce the idea of "atoms," non-overlapping sets based on the original pre-defined set annotations. Our approach focuses on finding the union of atoms that minimizes a weighted average of the number of false discoveries and missed discoveries. We introduce a new false discovery rate for sets, called the atomic false discovery rate (afdr), and prove that the optimal estimator in our decision-theory framework is to threshold the afdr. These results provide a coherent and interpretable framework for the analysis of sets that addresses the key issues of overlapping annotations and difficulty in interpreting p values in both competitive and self-contained tests. We illustrate our method and compare it to a popular existing method using simulated examples, as well as gene-set and brain ROI data analyses. VL - 69 N1 - http://www.ncbi.nlm.nih.gov/pubmed/23909925?dopt=Abstract ER - TY - JOUR T1 - Derepression of Cancer/testis antigens in cancer is associated with distinct patterns of DNA hypomethylation JF - BMC CancerBMC CancerBMC Cancer Y1 - 2013 A1 - Kim, R. A1 - Kulkarni, P. A1 - Sridhar Hannenhalli KW - *DNA Methylation KW - *Gene Expression Regulation, Neoplastic KW - *Genes, X-Linked KW - Antigens, Neoplasm/*genetics KW - Binding Sites KW - Cluster Analysis KW - CpG Islands KW - Gene Expression Profiling KW - HUMANS KW - Male KW - Neoplasms/*genetics/*metabolism KW - Promoter Regions, Genetic KW - Protein Binding KW - Protein Interaction Domains and Motifs KW - Testis/*metabolism AB - BACKGROUND: The Cancer/Testis Antigens (CTAs) are a heterogeneous group of proteins whose expression is typically restricted to the testis. However, they are aberrantly expressed in most cancers that have been examined to date. Broadly speaking, the CTAs can be divided into two groups: the CTX antigens that are encoded by the X-linked genes and the non-X CT antigens that are encoded by the autosomes. Unlike the non-X CTAs, the CTX antigens form clusters of closely related gene families and their expression is frequently associated with advanced disease with poorer prognosis. Regardless however, the mechanism(s) underlying their selective derepression and stage-specific expression in cancer remain poorly understood, although promoter DNA demethylation is believed to be the major driver. METHODS: Here, we report a systematic analysis of DNA methylation profiling data from various tissue types to elucidate the mechanism underlying the derepression of the CTAs in cancer. We analyzed the methylation profiles of 501 samples including sperm, several cancer types, and their corresponding normal somatic tissue types. RESULTS: We found strong evidence for specific DNA hypomethylation of CTA promoters in the testis and cancer cells but not in their normal somatic counterparts. We also found that hypomethylation was clustered on the genome into domains that coincided with nuclear lamina-associated domains (LADs) and that these regions appeared to be insulated by CTCF sites. Interestingly, we did not observe any significant differences in the hypomethylation pattern between the CTAs without CpG islands and the CTAs with CpG islands in the proximal promoter. CONCLUSION: Our results corroborate that widespread DNA hypomethylation appears to be the driver in the derepression of CTA expression in cancer and furthermore, demonstrate that these hypomethylated domains are associated with the nuclear lamina-associated domains (LADS). Taken together, our results suggest that wide-spread methylation changes in cancer are linked to derepression of germ-line-specific genes that is orchestrated by the three dimensional organization of the cancer genome. VL - 13 SN - 1471-2407 (Electronic)
1471-2407 (Linking) N1 - Kim, Robert
Kulkarni, Prakash
Hannenhalli, Sridhar
eng
R01 GM100335/GM/NIGMS NIH HHS/
R01GM100335/GM/NIGMS NIH HHS/
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
England
2013/03/26 06:00
BMC Cancer. 2013 Mar 22;13:144. doi: 10.1186/1471-2407-13-144. U2 - 3618251 J1 - BMC cancerBMC cancer ER - TY - JOUR T1 - Differential abundance analysis for microbial marker-gene surveys JF - Nature methods Y1 - 2013 A1 - Joseph N. Paulson A1 - Stine, O. Colin A1 - Héctor Corrada Bravo A1 - M. Pop AB - We introduce a methodology to assess differential abundance in sparse high-throughput microbial marker-gene survey data. Our approach, implemented in the metagenomeSeq Bioconductor package, relies on a novel normalization technique and a statistical model that accounts for undersampling—a common feature of large-scale marker-gene studies. Using simulated data and several published microbiota data sets, we show that metagenomeSeq outperforms the tools currently used in this field. PB - Nature Publishing Group VL - 10 SN - 1548-7091 UR - http://www.nature.com/nmeth/journal/v10/n12/full/nmeth.2658.html M3 - 10.1038/nmeth.2658 ER - TY - JOUR T1 - Distinct Rap1 activity states control the extent of epithelial invagination via α-catenin. JF - Dev Cell Y1 - 2013 A1 - Wang, Yu-Chiun A1 - Khan, Zia A1 - Wieschaus, Eric F KW - Actins KW - alpha Catenin KW - Animals KW - Cell Adhesion KW - Cell Adhesion Molecules KW - Cell Membrane KW - Cell Shape KW - Drosophila KW - Drosophila Proteins KW - Embryo, Nonmammalian KW - Enzyme Activation KW - Epithelial Cells KW - Genes, Insect KW - Green Fluorescent Proteins KW - GTP Phosphohydrolases KW - GTPase-Activating Proteins KW - Intercellular Junctions KW - RNA Interference KW - Time factors KW - Time-Lapse Imaging AB -

Localized cell shape change initiates epithelial folding, while neighboring cell invagination determines the final depth of an epithelial fold. The mechanism that controls the extent of invagination remains unknown. During Drosophila gastrulation, a higher number of cells undergo invagination to form the deep posterior dorsal fold, whereas far fewer cells become incorporated into the initially very similar anterior dorsal fold. We find that a decrease in α-catenin activity causes the anterior fold to invaginate as extensively as the posterior fold. In contrast, constitutive activation of the small GTPase Rap1 restricts invagination of both dorsal folds in an α-catenin-dependent manner. Rap1 activity appears spatially modulated by Rapgap1, whose expression levels are high in the cells that flank the posterior fold but low in the anterior fold. We propose a model whereby distinct activity states of Rap1 modulate α-catenin-dependent coupling between junctions and actin to control the extent of epithelial invagination.

VL - 25 CP - 3 M3 - 10.1016/j.devcel.2013.04.002 ER - TY - Generic T1 - Distinct Rap1 Activity States Control the Extent of Epithelial Invagination via α-Catenin Y1 - 2013 A1 - Wang, Yu-Chiun A1 - Khan, Zia A1 - Wieschaus,  F. JA - Developmental Cell VL - 25 UR - http://linkinghub.elsevier.com/retrieve/pii/S1534580713001937http://api.elsevier.com/content/article/PII:S1534580713001937?httpAccept=text/xmlhttp://api.elsevier.com/content/article/PII:S1534580713001937?httpAccept=text/plain CP - 3 J1 - Developmental Cell M3 - 10.1016/j.devcel.2013.04.002 ER - TY - JOUR T1 - Enhancer networks revealed by correlated DNAse hypersensitivity states of enhancers JF - Nucleic Acids ResNucleic Acids ResNucleic Acids Res Y1 - 2013 A1 - Malin, J. A1 - Aniba, M. R. A1 - Sridhar Hannenhalli KW - *Deoxyribonucleases KW - *Enhancer Elements, Genetic KW - Chromatin/chemistry KW - Gene expression KW - Gene Regulatory Networks KW - HUMANS KW - Transcription Factors/metabolism AB - Mammalian gene expression is often regulated by distal enhancers. However, little is known about higher order functional organization of enhancers. Using approximately 100 K P300-bound regions as candidate enhancers, we investigated their correlated activity across 72 cell types based on DNAse hypersensitivity. We found widespread correlated activity between enhancers, which decreases with increasing inter-enhancer genomic distance. We found that correlated enhancers tend to share common transcription factor (TF) binding motifs, and several chromatin modification enzymes preferentially interact with these TFs. Presence of shared motifs in enhancer pairs can predict correlated activity with 73% accuracy. Also, genes near correlated enhancers exhibit correlated expression and share common function. Correlated enhancers tend to be spatially proximal. Interestingly, weak enhancers tend to correlate with significantly greater numbers of other enhancers relative to strong enhancers. Furthermore, strong/weak enhancers preferentially correlate with strong/weak enhancers, respectively. We constructed enhancer networks based on shared motif and correlated activity and show significant functional enrichment in their putative target gene clusters. Overall, our analyses show extensive correlated activity among enhancers and reveal clusters of enhancers whose activities are coordinately regulated by multiple potential mechanisms involving shared TF binding, chromatin modifying enzymes and 3D chromatin structure, which ultimately co-regulate functionally linked genes. VL - 41 SN - 1362-4962 (Electronic)
0305-1048 (Linking) N1 - Malin, Justin
Aniba, Mohamed Radhouane
Hannenhalli, Sridhar
eng
R01 GM100335/GM/NIGMS NIH HHS/
R01GM100335/GM/NIGMS NIH HHS/
Research Support, N.I.H., Extramural
England
2013/05/24 06:00
Nucleic Acids Res. 2013 Aug;41(14):6828-38. doi: 10.1093/nar/gkt374. Epub 2013 May 21. U2 - 3737527 J1 - Nucleic acids researchNucleic acids research ER - TY - JOUR T1 - Exploring variation-aware contig graphs for (comparative) metagenomics using MaryGold JF - Bioinformatics (Oxford, England)Bioinformatics (Oxford, England) Y1 - 2013 A1 - Nijkamp, Jurgen F. A1 - M. Pop A1 - Reinders, Marcel J. T. A1 - de Ridder, Dick AB - MOTIVATION: Although many tools are available to study variation and its impact in single genomes, there is a lack of algorithms for finding such variation in metagenomes. This hampers the interpretation of metagenomics sequencing datasets, which are increasingly acquired in research on the (human) microbiome, in environmental studies and in the study of processes in the production of foods and beverages. Existing algorithms often depend on the use of reference genomes, which pose a problem when a metagenome of a priori unknown strain composition is studied. In this article, we develop a method to perform reference-free detection and visual exploration of genomic variation, both within a single metagenome and between metagenomes. RESULTS: We present the MaryGold algorithm and its implementation, which efficiently detects bubble structures in contig graphs using graph decomposition. These bubbles represent variable genomic regions in closely related strains in metagenomic samples. The variation found is presented in a condensed Circos-based visualization, which allows for easy exploration and interpretation of the found variation. We validated the algorithm on two simulated datasets containing three respectively seven Escherichia coli genomes and showed that finding allelic variation in these genomes improves assemblies. Additionally, we applied MaryGold to publicly available real metagenomic datasets, enabling us to find within-sample genomic variation in the metagenomes of a kimchi fermentation process, the microbiome of a premature infant and in microbial communities living on acid mine drainage. Moreover, we used MaryGold for between-sample variation detection and exploration by comparing sequencing data sampled at different time points for both of these datasets. AVAILABILITY: MaryGold has been written in C++ and Python and can be downloaded from http://bioinformatics.tudelft.nl/software VL - 29 N1 - http://www.ncbi.nlm.nih.gov/pubmed/24058058?dopt=Abstract ER - TY - JOUR T1 - Genetic loci associated with delayed clearance of Plasmodium falciparum following artemisinin treatment in Southeast Asia JF - Proceedings of the National Academy of Sciences of the United States of AmericaProceedings of the National Academy of Sciences of the United States of America Y1 - 2013 A1 - Takala-Harrison, Shannon A1 - Clark, Taane G. A1 - Jacob, Christopher G. A1 - Michael P. Cummings A1 - Miotto, Olivo A1 - Dondorp, Arjen M. A1 - Fukuda, Mark M. A1 - Nosten, Francois A1 - Noedl, Harald A1 - Imwong, Mallika A1 - Bethell, Delia A1 - Se, Youry A1 - Lon, Chanthap A1 - Tyner, Stuart D. A1 - Saunders, David L. A1 - Socheat, Duong A1 - Ariey, Frederic A1 - Phyo, Aung Pyae A1 - Starzengruber, Peter A1 - Fuehrer, Hans-Peter A1 - Swoboda, Paul A1 - Stepniewska, Kasia A1 - Flegg, Jennifer A1 - Arze, Cesar A1 - Cerqueira, Gustavo C. A1 - Silva, Joana C. A1 - Ricklefs, Stacy M. A1 - Porcella, Stephen F. A1 - Stephens, Robert M. A1 - Adams, Matthew A1 - Kenefic, Leo J. A1 - Campino, Susana A1 - Auburn, Sarah A1 - Macinnis, Bronwyn A1 - Kwiatkowski, Dominic P. A1 - Su, Xin-Zhuan A1 - White, Nicholas J. A1 - Ringwald, Pascal A1 - Plowe, Christopher V. AB - The recent emergence of artemisinin-resistant Plasmodium falciparum malaria in western Cambodia could threaten prospects for malaria elimination. Identification of the genetic basis of resistance would provide tools for molecular surveillance, aiding efforts to contain resistance. Clinical trials of artesunate efficacy were conducted in Bangladesh, in northwestern Thailand near the Myanmar border, and at two sites in western Cambodia. Parasites collected from trial participants were genotyped at 8,079 single nucleotide polymorphisms (SNPs) using a P. falciparum-specific SNP array. Parasite genotypes were examined for signatures of recent positive selection and association with parasite clearance phenotypes to identify regions of the genome associated with artemisinin resistance. Four SNPs on chromosomes 10 (one), 13 (two), and 14 (one) were significantly associated with delayed parasite clearance. The two SNPs on chromosome 13 are in a region of the genome that appears to be under strong recent positive selection in Cambodia. The SNPs on chromosomes 10 and 13 lie in or near genes involved in postreplication repair, a DNA damage-tolerance pathway. Replication and validation studies are needed to refine the location of loci responsible for artemisinin resistance and to understand the mechanism behind it; however, two SNPs on chromosomes 10 and 13 may be useful markers of delayed parasite clearance in surveillance for artemisinin resistance in Southeast Asia. VL - 110 ER - TY - JOUR T1 - Genome sequence of the attenuated Carbosap vaccine strain of Bacillus anthracis JF - Genome announcements Y1 - 2013 A1 - Harrington, Robin A1 - Ondov, Brian D A1 - Radune, Diana A1 - Friss, Mary Beth A1 - Klubnik, Joy A1 - Diviak, Lynn A1 - Hnath, Jonathan A1 - Cendrowski, Stephen R A1 - Blank, Thomas E A1 - Karaolis, David A1 - Todd Treangen VL - 1 ER - TY - JOUR T1 - Genome sequencing of four strains of Rickettsia prowazekii, the causative agent of epidemic typhus, including one flying squirrel isolate JF - Genome announcementsGenome announcements Y1 - 2013 A1 - Bishop-Lilly, Kimberly A. A1 - Ge, Hong A1 - Butani, Amy A1 - Osborne, Brian A1 - Verratti, Kathleen A1 - Mokashi, Vishwesh A1 - Nagarajan, Niranjan A1 - M. Pop A1 - Read, Timothy D. A1 - Richards, Allen L. PB - American Society for Microbiology VL - 1 SN - 2169-8287 ER - TY - Generic T1 - Genomic analysis of sequence-dependent DNA curvature in Leishmania. Y1 - 2013 A1 - Smircich, Pablo A1 - Forteza, Diego A1 - El-Sayed, Najib M A1 - Garat, Beatriz KW - Chromosome mapping KW - Comparative Genomic Hybridization KW - Computational Biology KW - DNA, Protozoan KW - Genome, Protozoan KW - Genomics KW - HUMANS KW - Leishmania KW - Nucleic Acid Conformation AB -

Leishmania major is a flagellated protozoan parasite of medical importance. Like other members of the Trypanosomatidae family, it possesses unique mechanisms of gene expression such as constitutive polycistronic transcription of directional gene clusters, gene amplification, mRNA trans-splicing, and extensive editing of mitochondrial transcripts. The molecular signals underlying most of these processes remain under investigation. In order to investigate the role of DNA secondary structure signals in gene expression, we carried out a genome-wide in silico analysis of the intrinsic DNA curvature. The L. major genome revealed a lower frequency of high intrinsic curvature regions as well as inter- and intra- chromosomal distribution heterogeneity, when compared to prokaryotic and eukaryotic organisms. Using a novel method aimed at detecting region-integrated intrinsic curvature (RIIC), high DNA curvature was found to be associated with regions implicated in transcription initiation. Those include divergent strand-switch regions between directional gene clusters and regions linked to markers of active transcription initiation such as acetylated H3 histone, TRF4 and SNAP50. These findings suggest a role for DNA curvature in transcription initiation in Leishmania supporting the relevance of DNA secondary structures signals.

JA - PLoS One VL - 8 CP - 4 M3 - 10.1371/journal.pone.0063068 ER - TY - JOUR T1 - Hawkeye and AMOS: visualizing and assessing the quality of genome assemblies JF - Briefings in bioinformaticsBriefings in bioinformatics Y1 - 2013 A1 - Schatz, Michael C. A1 - Phillippy, Adam M. A1 - Sommer, Daniel D. A1 - Delcher, Arthur L. A1 - Puiu, Daniela A1 - Narzisi, Giuseppe A1 - Salzberg, Steven L. A1 - M. Pop PB - Oxford University Press VL - 14 ER - TY - CONF T1 - Identification of gene clusters with phenotype-dependent expression with application to normal and premature ageing T2 - Proceedings of the International Conference on Bioinformatics, Computational Biology and Biomedical Informatics Y1 - 2013 A1 - Kun Wang A1 - Avinash Das A1 - Zheng-Mei Xiong A1 - Kan Cao A1 - Sridhar Hannenhalli JA - Proceedings of the International Conference on Bioinformatics, Computational Biology and Biomedical Informatics PB - ACM CY - Wshington DC, USA U1 - 2506652 ER - TY - JOUR T1 - Intrinsically disordered proteins and conformational noise: Implications in cancer JF - Cell CycleCell Cycle Y1 - 2013 A1 - Mahmoudabadi, Gita A1 - Rajagopalan, Krithika A1 - Getzenberg, Robert H. A1 - Sridhar Hannenhalli A1 - Rangarajan, Govindan A1 - Kulkarni, Prakash VL - 12 N1 - cc ER - TY - ABST T1 - K-mulus: Strategies for BLAST in the cloud Y1 - 2013 A1 - Christopher M. Hill A1 - Albach, Carl H. A1 - Angel, Sebastian A1 - M. Pop JA - 10th International Conference on Parallel Processing and Applied Mathematics (PPAM) ER - TY - JOUR T1 - A large-scale, higher-level, molecular phylogenetic study of the insect order Lepidoptera (moths and butterflies) JF - PLoS OnePLoS One Y1 - 2013 A1 - Regier, Jerome C. A1 - Mitter, Charles A1 - Zwick, Andreas A1 - Adam L. Bazinet A1 - Michael P. Cummings A1 - Kawahara, Akito Y. A1 - Sohn, Jae-Cheon A1 - Zwickl, Derrick J. A1 - Cho, Soowon A1 - Davis, Donald R. A1 - Baixeras, Joaquin A1 - Brown, John A1 - Parr, Cynthia A1 - Weller, Susan A1 - Lees, David C. A1 - Mitter, Kim T. KW - Animals KW - Butterflies KW - Moths KW - Phylogeny AB -

BACKGROUND: Higher-level relationships within the Lepidoptera, and particularly within the species-rich subclade Ditrysia, are generally not well understood, although recent studies have yielded progress. We present the most comprehensive molecular analysis of lepidopteran phylogeny to date, focusing on relationships among superfamilies.

METHODOLOGY PRINCIPAL FINDINGS: 483 taxa spanning 115 of 124 families were sampled for 19 protein-coding nuclear genes, from which maximum likelihood tree estimates and bootstrap percentages were obtained using GARLI. Assessment of heuristic search effectiveness showed that better trees and higher bootstrap percentages probably remain to be discovered even after 1000 or more search replicates, but further search proved impractical even with grid computing. Other analyses explored the effects of sampling nonsynonymous change only versus partitioned and unpartitioned total nucleotide change; deletion of rogue taxa; and compositional heterogeneity. Relationships among the non-ditrysian lineages previously inferred from morphology were largely confirmed, plus some new ones, with strong support. Robust support was also found for divergences among non-apoditrysian lineages of Ditrysia, but only rarely so within Apoditrysia. Paraphyly for Tineoidea is strongly supported by analysis of nonsynonymous-only signal; conflicting, strong support for tineoid monophyly when synonymous signal was added back is shown to result from compositional heterogeneity. CONCLUSIONS SIGNIFICANCE: Support for among-superfamily relationships outside the Apoditrysia is now generally strong. Comparable support is mostly lacking within Apoditrysia, but dramatically increased bootstrap percentages for some nodes after rogue taxon removal, and concordance with other evidence, strongly suggest that our picture of apoditrysian phylogeny is approximately correct. This study highlights the challenge of finding optimal topologies when analyzing hundreds of taxa. It also shows that some nodes get strong support only when analysis is restricted to nonsynonymous change, while total change is necessary for strong support of others. Thus, multiple types of analyses will be necessary to fully resolve lepidopteran phylogeny.

VL - 8 ER - TY - JOUR T1 - MetAMOS: a modular and open source metagenomic assembly and analysis pipeline JF - Genome BiolGenome Biol Y1 - 2013 A1 - Todd Treangen A1 - Koren, S. A1 - Sommer, D. D. A1 - Liu, B. A1 - Irina Astrovskaya A1 - Ondov, B. A1 - Darling, A. E. A1 - Phillippy, A. M. A1 - M. Pop AB - ABSTRACT: We describe MetAMOS, an open source and modular metagenomic assembly and analysis pipeline. MetAMOS represents an important step towards fully automated metagenomic analysis, starting with next-generation sequencing reads and producing genomic scaffolds, open-reading frames and taxonomic or functional annotations. MetAMOS can aid in reducing assembly errors, commonly encountered when assembling metagenomic samples, and improves taxonomic assignment accuracy while also reducing computational cost. MetAMOS can be downloaded from: https://github.com/treangen/MetAMOS. VL - 14 SN - 1465-6914 (Electronic)1465-6906 (Linking) N1 - Treangen, Todd JKoren, SergeySommer, Daniel DLiu, BoAstrovskaya, IrinaOndov, BrianDarling, Aaron EPhillippy, Adam MPop, MihaiGenome Biol. 2013 Jan 15;14(1):R2.
Genome biology ER - TY - JOUR T1 - A molecular phylogeny for Yponomeutoidea (Insecta, Lepidoptera, Ditrysia) and its implications for classification, biogeography and\ the evolution of host plant use JF - PLoS One Y1 - 2013 A1 - J. C. Sohn A1 - Regier, J. C. A1 - Mitter, C. A1 - D. Davis A1 - J. F. Landry A1 - Zwick, A. A1 - Michael P. Cummings ER - TY - JOUR T1 - Primate transcript and protein expression levels evolve under compensatory selection pressures. JF - Science Y1 - 2013 A1 - Khan, Zia A1 - Ford, Michael J A1 - Cusanovich, Darren A A1 - Mitrano, Amy A1 - Pritchard, Jonathan K A1 - Gilad, Yoav KW - Animals KW - Evolution, Molecular KW - Gene Expression Regulation KW - HUMANS KW - Macaca mulatta KW - Pan troglodytes KW - Protein Biosynthesis KW - RNA, Messenger KW - Selection, Genetic KW - Species Specificity KW - Transcription, Genetic AB -

Changes in gene regulation have likely played an important role in the evolution of primates. Differences in messenger RNA (mRNA) expression levels across primates have often been documented; however, it is not yet known to what extent measurements of divergence in mRNA levels reflect divergence in protein expression levels, which are probably more important in determining phenotypic differences. We used high-resolution, quantitative mass spectrometry to collect protein expression measurements from human, chimpanzee, and rhesus macaque lymphoblastoid cell lines and compared them to transcript expression data from the same samples. We found dozens of genes with significant expression differences between species at the mRNA level yet little or no difference in protein expression. Overall, our data suggest that protein expression levels evolve under stronger evolutionary constraint than mRNA levels.

VL - 342 CP - 6162 M3 - 10.1126/science.1242379 ER - TY - Generic T1 - Primate Transcript and Protein Expression Levels Evolve Under Compensatory Selection Pressures Y1 - 2013 A1 - Khan, Z. A1 - Ford, M. J. A1 - Cusanovich, D. A. A1 - Mitrano, A. A1 - Pritchard, J. K. A1 - Gilad, Y. JA - Science VL - 342 UR - http://www.sciencemag.org/cgi/doi/10.1126/science.1242379 CP - 6162 J1 - Science M3 - 10.1126/science.1242379 ER - TY - JOUR T1 - Quantitative PCR for Detection of Shigella Improves Ascertainment of Shigella Burden in Children with Moderate-to-Severe Diarrhea in Low-Income Countries JF - Journal of Clinical MicrobiologyJournal of Clinical Microbiology Y1 - 2013 A1 - Lindsay, Brianna A1 - Ochieng, John B. A1 - Ikumapayi, Usman N. A1 - Toure, Aliou A1 - Ahmed, Dilruba A1 - Li, Shan A1 - Panchalingam, Sandra A1 - Levine, Myron M. A1 - Kotloff, Karen A1 - Rasko, David A. PB - American Society for Microbiology VL - 51 SN - 0095-1137 ER - TY - JOUR T1 - Re-evaluation of the Doriopsilla areolata Bergh, 1880 (Mollusca: Opisthobranchia) subspecies complex in the eastern Atlantic Ocean and its relationship to South African Doriopsilla miniata (Alder & Hancock, 1864) based on molecular data JF - Marine Biodiversity Y1 - 2013 A1 - Goodheart, Jessica A1 - Valdés, Ángel VL - 43 UR - http://link.springer.com/10.1007/s12526-012-0136-1http://link.springer.com/content/pdf/10.1007/s12526-012-0136-1 CP - 2 J1 - Mar Biodiv M3 - 10.1007/s12526-012-0136-1 ER - TY - BOOK T1 - Sea Slug Systematics: Using Molecular and Morphological Tools to Infer Species Relationships in Opisthobracnchs Y1 - 2013 A1 - Goodheart, Jessica A1 - California State Polytechnic University, Pomona. Department of Biological Sciences PB - California State Polytechnic University, Pomona UR - https://books.google.com/books?id=LZw3nwEACAAJ ER - TY - JOUR T1 - Sequence assembly demystified JF - Nature Reviews GeneticsNature Reviews Genetics Y1 - 2013 A1 - Nagarajan, Niranjan A1 - M. Pop PB - Nature Publishing Group VL - 14 SN - 1471-0056 ER - TY - JOUR T1 - Somatic alterations contributing to metastasis of a castration-resistant prostate cancer JF - Human mutationHuman mutation Y1 - 2013 A1 - Nickerson, Michael L. A1 - Im, Kate M. A1 - Misner, Kevin J. A1 - Tan, Wei A1 - Lou, Hong A1 - Gold, Bert A1 - Wells, David W. A1 - Héctor Corrada Bravo A1 - Fredrikson, Karin M. A1 - Harkins, Timothy T. A1 - Milos, Patrice A1 - Zbar, Berton A1 - Linehan, W. Marston A1 - Yeager, Meredith A1 - Andresson, Thorkell A1 - Dean, Michael A1 - Bova, G. Steven AB - Metastatic castration-resistant prostate cancer (mCRPC) is a lethal disease, and molecular markers that differentiate indolent from aggressive subtypes are needed. We sequenced the exomes of five metastatic tumors and healthy kidney tissue from an index case with mCRPC to identify lesions associated with disease progression and metastasis. An Ashkenazi Jewish (AJ) germline founder mutation, del185AG in BRCA1, was observed and AJ ancestry was confirmed. Sixty-two somatic variants altered proteins in tumors, including cancer-associated genes, TMPRSS2-ERG, PBRM1, and TET2. The majority (n = 53) of somatic variants were present in all metastases and only a subset (n = 31) was observed in the primary tumor. Integrating tumor next-generation sequencing and DNA copy number showed somatic loss of BRCA1 and TMPRSS2-ERG. We sequenced 19 genes with deleterious mutations in the index case in additional mCRPC samples and detected a frameshift, two somatic missense alterations, tumor loss of heterozygosity, and combinations of germline missense SNPs in TET2. In summary, genetic analysis of metastases from an index case permitted us to infer a chronology for the clonal spread of disease based on sequential accrual of somatic lesions. The role of TET2 in mCRPC deserves additional analysis and may define a subset of metastatic disease. VL - 34 N1 - http://www.ncbi.nlm.nih.gov/pubmed/23636849?dopt=Abstract ER - TY - JOUR T1 - Survey of Culture, GoldenGate Assay, Universal Biosensor Assay, and 16S rRNA Gene Sequencing as Alternative Methods of Bacterial Pathogen Detection JF - Journal of Clinical MicrobiologyJournal of Clinical Microbiology Y1 - 2013 A1 - Lindsay, Brianna A1 - M. Pop A1 - Antonio, Martin A1 - Walker, Alan W. A1 - Mai, Volker A1 - Ahmed, Dilruba A1 - Oundo, Joseph A1 - Tamboura, Boubou A1 - Panchalingam, Sandra A1 - Levine, Myron M. PB - American Society for Microbiology VL - 51 SN - 0095-1137 ER - TY - JOUR T1 - Three independent determinants of protein evolutionary rate JF - J Mol EvolJ Mol EvolJ Mol Evol Y1 - 2013 A1 - Choi, S. S. A1 - Sridhar Hannenhalli KW - *Evolution, Molecular KW - *Mutation Rate KW - Animals KW - Genes/physiology KW - Genetic Fitness KW - HUMANS KW - Models, Genetic KW - Protein Biosynthesis/genetics KW - Protein Folding KW - Protein Interaction Domains and Motifs/genetics KW - Proteins/chemistry/*genetics/metabolism AB - One of the most widely accepted ideas related to the evolutionary rates of proteins is that functionally important residues or regions evolve slower than other regions, a reasonable outcome of which should be a slower evolutionary rate of the proteins with a higher density of functionally important sites. Oddly, the role of functional importance, mainly measured by essentiality, in determining evolutionary rate has been challenged in recent studies. Several variables other than protein essentiality, such as expression level, gene compactness, protein-protein interactions, etc., have been suggested to affect protein evolutionary rate. In the present review, we try to refine the concept of functional importance of a gene, and consider three factors-functional importance, expression level, and gene compactness, as independent determinants of evolutionary rate of a protein, based not only on their known correlation with evolutionary rate but also on a reasonable mechanistic model. We suggest a framework based on these mechanistic models to correctly interpret the correlations between evolutionary rates and the various variables as well as the interrelationships among the variables. VL - 76 SN - 1432-1432 (Electronic)
0022-2844 (Linking) N1 - Choi, Sun Shim
Hannenhalli, Sridhar
eng
R01GM085226/GM/NIGMS NIH HHS/
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review
Germany
2013/02/13 06:00
J Mol Evol. 2013 Mar;76(3):98-111. doi: 10.1007/s00239-013-9543-6. Epub 2013 Feb 12. J1 - Journal of molecular evolutionJournal of molecular evolution ER - TY - JOUR T1 - TIGRFAMs and Genome Properties in 2013 JF - Nucleic acids researchNucleic Acids Research Y1 - 2013 A1 - Haft, Daniel H. A1 - J. Selengut A1 - Richter, Roland A. A1 - Harkins, Derek A1 - Basu, Malay K. A1 - Beck, Erin KW - Databases, Protein KW - Genome, Archaeal KW - Genome, Bacterial KW - Genomics KW - Internet KW - Markov chains KW - Molecular Sequence Annotation KW - Proteins KW - sequence alignment AB - TIGRFAMs, available online at http://www.jcvi.org/tigrfams is a database of protein family definitions. Each entry features a seed alignment of trusted representative sequences, a hidden Markov model (HMM) built from that alignment, cutoff scores that let automated annotation pipelines decide which proteins are members, and annotations for transfer onto member proteins. Most TIGRFAMs models are designated equivalog, meaning they assign a specific name to proteins conserved in function from a common ancestral sequence. Models describing more functionally heterogeneous families are designated subfamily or domain, and assign less specific but more widely applicable annotations. The Genome Properties database, available at http://www.jcvi.org/genome-properties, specifies how computed evidence, including TIGRFAMs HMM results, should be used to judge whether an enzymatic pathway, a protein complex or another type of molecular subsystem is encoded in a genome. TIGRFAMs and Genome Properties content are developed in concert because subsystems reconstruction for large numbers of genomes guides selection of seed alignment sequences and cutoff values during protein family construction. Both databases specialize heavily in bacterial and archaeal subsystems. At present, 4284 models appear in TIGRFAMs, while 628 systems are described by Genome Properties. Content derives both from subsystem discovery work and from biocuration of the scientific literature. VL - 41 N1 - http://www.ncbi.nlm.nih.gov/pubmed/23197656?dopt=Abstract ER - TY - JOUR T1 - TIGRFAMs and Genome Properties in 2013. JF - Nucleic Acids Res Y1 - 2013 A1 - Haft, Daniel H A1 - Selengut, Jeremy D A1 - Richter, Roland A A1 - Harkins, Derek A1 - Basu, Malay K A1 - Beck, Erin KW - Databases, Protein KW - Genome, Archaeal KW - Genome, Bacterial KW - Genomics KW - Internet KW - Markov chains KW - Molecular Sequence Annotation KW - Proteins KW - sequence alignment AB -

TIGRFAMs, available online at http://www.jcvi.org/tigrfams is a database of protein family definitions. Each entry features a seed alignment of trusted representative sequences, a hidden Markov model (HMM) built from that alignment, cutoff scores that let automated annotation pipelines decide which proteins are members, and annotations for transfer onto member proteins. Most TIGRFAMs models are designated equivalog, meaning they assign a specific name to proteins conserved in function from a common ancestral sequence. Models describing more functionally heterogeneous families are designated subfamily or domain, and assign less specific but more widely applicable annotations. The Genome Properties database, available at http://www.jcvi.org/genome-properties, specifies how computed evidence, including TIGRFAMs HMM results, should be used to judge whether an enzymatic pathway, a protein complex or another type of molecular subsystem is encoded in a genome. TIGRFAMs and Genome Properties content are developed in concert because subsystems reconstruction for large numbers of genomes guides selection of seed alignment sequences and cutoff values during protein family construction. Both databases specialize heavily in bacterial and archaeal subsystems. At present, 4284 models appear in TIGRFAMs, while 628 systems are described by Genome Properties. Content derives both from subsystem discovery work and from biocuration of the scientific literature.

VL - 41 CP - Database issue M3 - 10.1093/nar/gks1234 ER - TY - CONF T1 - Topological properties of chromosome conformation graphs reflect spatial proximities within chromatin T2 - Proceedings of the International Conference on Bioinformatics, Computational Biology and Biomedical Informatics Y1 - 2013 A1 - Hao Wang A1 - Geet Duggal A1 - Rob Patro A1 - Michelle Girvan A1 - Sridhar Hannenhalli A1 - Carl Kingsford JA - Proceedings of the International Conference on Bioinformatics, Computational Biology and Biomedical Informatics PB - ACM CY - Wshington DC, USA U1 - 2506633 ER - TY - JOUR T1 - AGORA: Assembly Guided by Optical Restriction Alignment JF - BMC bioinformaticsBMC Bioinformatics Y1 - 2012 A1 - Lin, H. C. A1 - Goldstein, S. A1 - L. Mendelowitz A1 - Zhou, S. A1 - Wetzel, J. A1 - Schwartz, D. C. A1 - M. Pop PB - BioMed Central Ltd VL - 13 ER - TY - JOUR T1 - Archaeosortases and exosortases are widely distributed systems linking membrane transit with posttranslational modification JF - Journal of bacteriologyJournal of bacteriology Y1 - 2012 A1 - Haft, Daniel H. A1 - Payne, Samuel H. A1 - J. Selengut KW - Amino Acid Sequence KW - Aminoacyltransferases KW - Archaeal Proteins KW - Bacterial Proteins KW - Cell Membrane KW - Cysteine Endopeptidases KW - Gene Expression Regulation, Archaeal KW - Gene Expression Regulation, Bacterial KW - Gene Expression Regulation, Enzymologic KW - Molecular Sequence Data KW - Protein Processing, Post-Translational AB - Multiple new prokaryotic C-terminal protein-sorting signals were found that reprise the tripartite architecture shared by LPXTG and PEP-CTERM: motif, TM helix, basic cluster. Defining hidden Markov models were constructed for all. PGF-CTERM occurs in 29 archaeal species, some of which have more than 50 proteins that share the domain. PGF-CTERM proteins include the major cell surface protein in Halobacterium, a glycoprotein with a partially characterized diphytanylglyceryl phosphate linkage near its C terminus. Comparative genomics identifies a distant exosortase homolog, designated archaeosortase A (ArtA), as the likely protein-processing enzyme for PGF-CTERM. Proteomics suggests that the PGF-CTERM region is removed. Additional systems include VPXXXP-CTERM/archeaosortase B in two of the same archaea and PEF-CTERM/archaeosortase C in four others. Bacterial exosortases often fall into subfamilies that partner with very different cohorts of extracellular polymeric substance biosynthesis proteins; several species have multiple systems. Variant systems include the VPDSG-CTERM/exosortase C system unique to certain members of the phylum Verrucomicrobia, VPLPA-CTERM/exosortase D in several alpha- and deltaproteobacterial species, and a dedicated (single-target) VPEID-CTERM/exosortase E system in alphaproteobacteria. Exosortase-related families XrtF in the class Flavobacteria and XrtG in Gram-positive bacteria mark distinctive conserved gene neighborhoods. A picture emerges of an ancient and now well-differentiated superfamily of deeply membrane-embedded protein-processing enzymes. Their target proteins are destined to transit cellular membranes during their biosynthesis, during which most undergo additional posttranslational modifications such as glycosylation. VL - 194 N1 - http://www.ncbi.nlm.nih.gov/pubmed/22037399?dopt=Abstract ER - TY - JOUR T1 - Archaeosortases and exosortases are widely distributed systems linking membrane transit with posttranslational modification. JF - J Bacteriol Y1 - 2012 A1 - Haft, Daniel H A1 - Payne, Samuel H A1 - Selengut, Jeremy D KW - Amino Acid Sequence KW - Aminoacyltransferases KW - Archaeal Proteins KW - Bacterial Proteins KW - Cell Membrane KW - Cysteine Endopeptidases KW - Gene Expression Regulation, Archaeal KW - Gene Expression Regulation, Bacterial KW - Gene Expression Regulation, Enzymologic KW - Molecular Sequence Data KW - Protein Processing, Post-Translational AB -

Multiple new prokaryotic C-terminal protein-sorting signals were found that reprise the tripartite architecture shared by LPXTG and PEP-CTERM: motif, TM helix, basic cluster. Defining hidden Markov models were constructed for all. PGF-CTERM occurs in 29 archaeal species, some of which have more than 50 proteins that share the domain. PGF-CTERM proteins include the major cell surface protein in Halobacterium, a glycoprotein with a partially characterized diphytanylglyceryl phosphate linkage near its C terminus. Comparative genomics identifies a distant exosortase homolog, designated archaeosortase A (ArtA), as the likely protein-processing enzyme for PGF-CTERM. Proteomics suggests that the PGF-CTERM region is removed. Additional systems include VPXXXP-CTERM/archeaosortase B in two of the same archaea and PEF-CTERM/archaeosortase C in four others. Bacterial exosortases often fall into subfamilies that partner with very different cohorts of extracellular polymeric substance biosynthesis proteins; several species have multiple systems. Variant systems include the VPDSG-CTERM/exosortase C system unique to certain members of the phylum Verrucomicrobia, VPLPA-CTERM/exosortase D in several alpha- and deltaproteobacterial species, and a dedicated (single-target) VPEID-CTERM/exosortase E system in alphaproteobacteria. Exosortase-related families XrtF in the class Flavobacteria and XrtG in Gram-positive bacteria mark distinctive conserved gene neighborhoods. A picture emerges of an ancient and now well-differentiated superfamily of deeply membrane-embedded protein-processing enzymes. Their target proteins are destined to transit cellular membranes during their biosynthesis, during which most undergo additional posttranslational modifications such as glycosylation.

VL - 194 CP - 1 M3 - 10.1128/JB.06026-11 ER - TY - JOUR T1 - BclAF1 restriction factor is neutralized by proteasomal degradation and microRNA repression during human cytomegalovirus infection. JF - Proc Natl Acad Sci U S A Y1 - 2012 A1 - Lee, Song Hee A1 - Kalejta, Robert F A1 - Kerry, Julie A1 - Semmes, Oliver John A1 - O'Connor, Christine M A1 - Khan, Zia A1 - Garcia, Benjamin A A1 - Shenk, Thomas A1 - Murphy, Eain KW - Cytomegalovirus KW - Cytomegalovirus Infections KW - Genes, Immediate-Early KW - HUMANS KW - Hydrolysis KW - MicroRNAs KW - Proteasome Endopeptidase Complex KW - Repressor Proteins KW - Tumor Suppressor Proteins AB -

Cell proteins can restrict the replication of viruses. Here, we identify the cellular BclAF1 protein as a human cytomegalovirus restriction factor and describe two independent mechanisms the virus uses to decrease its steady-state levels. Immediately following infection, the viral pp71 and UL35 proteins, which are delivered to cells within virions, direct the proteasomal degradation of BclAF1. Although BclAF1 reaccumulates through the middle stages of infection, it is subsequently down-regulated at late times by miR-UL112-1, a virus-encoded microRNA. In the absence of BclAF1 neutralization, viral gene expression and replication are inhibited. These data identify two temporally and mechanistically distinct functions used by human cytomegalovirus to down-regulate a cellular antiviral protein.

VL - 109 CP - 24 M3 - 10.1073/pnas.1207496109 ER - TY - Generic T1 - BclAF1 restriction factor is neutralized by proteasomal degradation and microRNA repression during human cytomegalovirus infection Y1 - 2012 A1 - Lee, S. H. A1 - Kalejta, R. F. A1 - Kerry, J. A1 - Semmes, O. J. A1 - O'Connor, C. M. A1 - Khan, Z. A1 - Garcia, B. A. A1 - Shenk, T. A1 - Murphy, E. JA - Proceedings of the National Academy of Sciences VL - 109 UR - http://www.pnas.org/cgi/doi/10.1073/pnas.1207496109 CP - 24 J1 - Proceedings of the National Academy of Sciences M3 - 10.1073/pnas.1207496109 ER - TY - JOUR T1 - BclAF1 restriction factor is neutralized by proteasomal degradation and microRNA repression during human cytomegalovirus infection JF - Proceedings of the National Academy of Sciences Y1 - 2012 A1 - Lee, S. H. A1 - Kalejta, R. F. A1 - Kerry, J. A1 - Semmes, O. J. A1 - O'Connor, C. M. A1 - Khan, Z. A1 - Garcia, B. A. A1 - Shenk, T. A1 - Murphy, E. VL - 109 UR - http://www.pnas.org/cgi/doi/10.1073/pnas.1207496109 CP - 24 J1 - Proceedings of the National Academy of Sciences M3 - 10.1073/pnas.1207496109 ER - TY - JOUR T1 - BEAGLE: An Application Programming Interface and High-Performance Computing Library for Statistical Phylogenetics JF - Systematic BiologySyst BiolSystematic BiologySyst Biol Y1 - 2012 A1 - Ayres, Daniel L. A1 - Darling, Aaron A1 - Zwickl, Derrick J. A1 - Beerli, Peter A1 - Holder, Mark T. A1 - Lewis, Paul O. A1 - Huelsenbeck, John P. A1 - Ronquist, Fredrik A1 - Swofford, David L. A1 - Michael P. Cummings A1 - Rambaut, Andrew A1 - Suchard, Marc A. KW - Bayesian phylogenetics KW - gpu KW - maximum likelihood KW - parallel computing AB - Phylogenetic inference is fundamental to our understanding of most aspects of the origin and evolution of life, and in recent years, there has been a concentration of interest in statistical approaches such as Bayesian inference and maximum likelihood estimation. Yet, for large data sets and realistic or interesting models of evolution, these approaches remain computationally demanding. High-throughput sequencing can yield data for thousands of taxa, but scaling to such problems using serial computing often necessitates the use of nonstatistical or approximate approaches. The recent emergence of graphics processing units (GPUs) provides an opportunity to leverage their excellent floating-point computational performance to accelerate statistical phylogenetic inference. A specialized library for phylogenetic calculation would allow existing software packages to make more effective use of available computer hardware, including GPUs. Adoption of a common library would also make it easier for other emerging computing architectures, such as field programmable gate arrays, to be used in the future. We present BEAGLE, an application programming interface (API) and library for high-performance statistical phylogenetic inference. The API provides a uniform interface for performing phylogenetic likelihood calculations on a variety of compute hardware platforms. The library includes a set of efficient implementations and can currently exploit hardware including GPUs using NVIDIA CUDA, central processing units (CPUs) with Streaming SIMD Extensions and related processor supplementary instruction sets, and multicore CPUs via OpenMP. To demonstrate the advantages of a common API, we have incorporated the library into several popular phylogenetic software packages. The BEAGLE library is free open source software licensed under the Lesser GPL and available from http://beagle-lib.googlecode.com. An example client program is available as public domain software. VL - 61 SN - 1063-5157, 1076-836X ER - TY - JOUR T1 - Bioinformatics for the Human Microbiome Project JF - PLOS Computational BiologyPLOS Computational Biology Y1 - 2012 A1 - Gevers, Dirk A1 - M. Pop A1 - Schloss, Patrick D. A1 - Huttenhower, Curtis PB - Public Library of Science VL - 8 SN - 1553-7358 ER - TY - JOUR T1 - A comparative evaluation of sequence classification programs JF - BMC BioinformaticsBMC Bioinformatics Y1 - 2012 A1 - Adam L. Bazinet A1 - Michael P. Cummings AB - Background A fundamental problem in modern genomics is to taxonomically or functionally classify DNA sequence fragments derived from environmental sampling (i.e., metagenomics). Several different methods have been proposed for doing this effectively and efficiently, and many have been implemented in software. In addition to varying their basic algorithmic approach to classification, some methods screen sequence reads for ’barcoding genes’ like 16S rRNA, or various types of protein-coding genes. Due to the sheer number and complexity of methods, it can be difficult for a researcher to choose one that is well-suited for a particular analysis. Results We divided the very large number of programs that have been released in recent years for solving the sequence classification problem into three main categories based on the general algorithm they use to compare a query sequence against a database of sequences. We also evaluated the performance of the leading programs in each category on data sets whose taxonomic and functional composition is known. Conclusions We found significant variability in classification accuracy, precision, and resource consumption of sequence classification programs when used to analyze various metagenomics data sets. However, we observe some general trends and patterns that will be useful to researchers who use sequence classification programs. VL - 13 ER - TY - JOUR T1 - Deep Sequencing of the Oral Microbiome Reveals Signatures of Periodontal Disease JF - PloS onePLoS One Y1 - 2012 A1 - Liu, B. A1 - Faller, L. L. A1 - Klitgord, N. A1 - Mazumdar, V. A1 - Ghodsi, M. A1 - Sommer, D. D. A1 - Gibbons, T. R. A1 - Todd Treangen A1 - Chang, Y. C. A1 - Li, S. A1 - others, PB - Public Library of Science VL - 7 ER - TY - Generic T1 - Differential positioning of adherens junctions is associated with initiation of epithelial folding Y1 - 2012 A1 - Wang, Yu-Chiun A1 - Khan, Zia A1 - Kaschube, Matthias A1 - Wieschaus, Eric F. JA - Nature VL - 484 UR - http://www.nature.com/doifinder/10.1038/nature10938 CP - 7394 J1 - Nature M3 - 10.1038/nature10938 ER - TY - JOUR T1 - Differential positioning of adherens junctions is associated with initiation of epithelial folding. JF - Nature Y1 - 2012 A1 - Wang, Yu-Chiun A1 - Khan, Zia A1 - Kaschube, Matthias A1 - Wieschaus, Eric F KW - Adherens Junctions KW - Animals KW - Cell Polarity KW - Cell Shape KW - Choristoma KW - Drosophila melanogaster KW - Drosophila Proteins KW - Epithelial Cells KW - Epithelium KW - Gastrula KW - Gastrulation KW - Glycogen Synthase Kinase 3 KW - Intracellular Signaling Peptides and Proteins KW - Protein-Serine-Threonine Kinases AB -

During tissue morphogenesis, simple epithelial sheets undergo folding to form complex structures. The prevailing model underlying epithelial folding involves cell shape changes driven by myosin-dependent apical constriction. Here we describe an alternative mechanism that requires differential positioning of adherens junctions controlled by modulation of epithelial apical-basal polarity. Using live embryo imaging, we show that before the initiation of dorsal transverse folds during Drosophila gastrulation, adherens junctions shift basally in the initiating cells, but maintain their original subapical positioning in the neighbouring cells. Junctional positioning in the dorsal epithelium depends on the polarity proteins Bazooka and Par-1. In particular, the basal shift that occurs in the initiating cells is associated with a progressive decrease in Par-1 levels. We show that uniform reduction of the activity of Bazooka or Par-1 results in uniform apical or lateral positioning of junctions and in each case dorsal fold initiation is abolished. In addition, an increase in the Bazooka/Par-1 ratio causes formation of ectopic dorsal folds. The basal shift of junctions not only alters the apical shape of the initiating cells, but also forces the lateral membrane of the adjacent cells to bend towards the initiating cells, thereby facilitating tissue deformation. Our data thus establish a direct link between modification of epithelial polarity and initiation of epithelial folding.

VL - 484 CP - 7394 M3 - 10.1038/nature10938 ER - TY - JOUR T1 - Drosophila Src regulates anisotropic apical surface growth to control epithelial tube size. JF - Nat Cell Biol Y1 - 2012 A1 - Nelson, Kevin S A1 - Khan, Zia A1 - Molnár, Imre A1 - Mihály, József A1 - Kaschube, Matthias A1 - Beitel, Greg J KW - Animals KW - Drosophila KW - Epithelium KW - src-Family Kinases AB -

Networks of epithelial and endothelial tubes are essential for the function of organs such as the lung, kidney and vascular system. The sizes and shapes of these tubes are highly regulated to match their individual functions. Defects in tube size can cause debilitating diseases such as polycystic kidney disease and ischaemia. It is therefore critical to understand how tube dimensions are regulated. Here we identify the tyrosine kinase Src as an instructive regulator of epithelial-tube length in the Drosophila tracheal system. Loss-of-function Src42 mutations shorten tracheal tubes, whereas Src42 overexpression elongates them. Surprisingly, Src42 acts distinctly from known tube-size pathways and regulates both the amount of apical surface growth and, with the conserved formin dDaam, the direction of growth. Quantitative three-dimensional image analysis reveals that Src42- and dDaam-mutant tracheal cells expand more in the circumferential than the axial dimension, resulting in tubes that are shorter in length-but larger in diameter-than wild-type tubes. Thus, Src42 and dDaam control tube dimensions by regulating the direction of anisotropic growth, a mechanism that has not previously been described.

VL - 14 CP - 5 M3 - 10.1038/ncb2467 ER - TY - Generic T1 - Drosophila Src regulates anisotropic apical surface growth to control epithelial tube size Y1 - 2012 A1 - Nelson, Kevin S. A1 - Khan, Zia A1 - ár, Imre A1 - ály, ózsef A1 - Kaschube, Matthias A1 - Beitel, Greg J. JA - Nature Cell Biology VL - 14 UR - http://www.nature.com/doifinder/10.1038/ncb2467 CP - 5 J1 - Nat Cell Biol M3 - 10.1038/ncb2467 ER - TY - JOUR T1 - Epigenomic model of cardiac enhancers with application to Genome wideassociation studies JF - Pacific Symposium on BiocomputingPacific Symposium on Biocomputing Y1 - 2012 A1 - Avinash, D. Sahu A1 - R. Aniba A1 - Y. C. Chang A1 - Sridhar Hannenhalli ER - TY - JOUR T1 - Exploiting sparseness in de novo genome assembly JF - BMC bioinformaticsBMC Bioinformatics Y1 - 2012 A1 - Chengxi Ye A1 - Ma, Z. S. A1 - Cannon, C. H. A1 - M. Pop A1 - Yu, D. W. PB - BioMed Central Ltd VL - 13 ER - TY - JOUR T1 - A framework for human microbiome research JF - NatureNature Y1 - 2012 A1 - Methé, B. A. A1 - Nelson, K. E. A1 - M. Pop A1 - Creasy, H. H. A1 - Giglio, M. G. A1 - Huttenhower, C. A1 - Gevers, D. A1 - Petrosino, J. F. A1 - Abubucker, S. A1 - Badger, J. H. A1 - others, VL - 486 ER - TY - JOUR T1 - A framework for human microbiome research JF - Nature Y1 - 2012 A1 - Human Microbiome Project Consortium A1 - Todd Treangen VL - 486 ER - TY - JOUR T1 - Functional Divergence of Gene Duplicates a Domain-centric view JF - BMC Evolutionary BiologyBMC Evolutionary Biology Y1 - 2012 A1 - Khaladkar, Mugdha A1 - Sridhar Hannenhalli ER - TY - JOUR T1 - Functional genomics of trypanosomatids. JF - Parasite Immunol Y1 - 2012 A1 - Choi, J A1 - El-Sayed, N M KW - Animals KW - Genome, Protozoan KW - Genomics KW - HUMANS KW - Proteome KW - Protozoan Proteins KW - Transcriptome KW - Trypanosomatina AB -

The decoding of the Tritryp reference genomes nearly 7 years ago provided a first peek into the biology of pathogenic trypanosomatids and a blueprint that has paved the way for genome-wide studies. Although 60-70% of the predicted protein coding genes in Trypanosoma brucei, Trypanosoma cruzi and Leishmania major remain unannotated, the functional genomics landscape is rapidly changing. Facilitated by the advent of next-generation sequencing technologies, improved structural and functional annotation and genes and their products are emerging. Information is also growing for the interactions between cellular components as transcriptomes, regulatory networks and metabolomes are characterized, ushering in a new era of systems biology. Simultaneously, the launch of comparative sequencing of multiple strains of kinetoplastids will finally lead to the investigation of a vast, yet to be explored, evolutionary and pathogenomic space.

VL - 34 CP - 2-3 M3 - 10.1111/j.1365-3024.2011.01347.x ER - TY - JOUR T1 - GAGE: A critical evaluation of genome assemblies and assembly algorithms JF - Genome researchGenome Research Y1 - 2012 A1 - Salzberg, S. L. A1 - Phillippy, A. M. A1 - Zimin, A. A1 - Puiu, D. A1 - Magoc, T. A1 - Koren, S. A1 - Todd Treangen A1 - Schatz, M. C. A1 - Delcher, A. L. A1 - Roberts, M. A1 - others, PB - Cold Spring Harbor Lab VL - 22 ER - TY - JOUR T1 - Gene expression anti-profiles as a basis for accurate universal cancer signatures JF - BMC bioinformaticsBMC Bioinformatics Y1 - 2012 A1 - Héctor Corrada Bravo A1 - Pihur, Vasyl A1 - McCall, Matthew A1 - Irizarry, Rafael A. A1 - Leek, Jeffrey T. KW - Area Under Curve KW - Colonic Neoplasms KW - Gene Expression Profiling KW - Genetic Variation KW - Genomics KW - HUMANS KW - Oligonucleotide Array Sequence Analysis KW - Prognosis KW - Transcriptome KW - Tumor Markers, Biological AB - BACKGROUND: Early screening for cancer is arguably one of the greatest public health advances over the last fifty years. However, many cancer screening tests are invasive (digital rectal exams), expensive (mammograms, imaging) or both (colonoscopies). This has spurred growing interest in developing genomic signatures that can be used for cancer diagnosis and prognosis. However, progress has been slowed by heterogeneity in cancer profiles and the lack of effective computational prediction tools for this type of data. RESULTS: We developed anti-profiles as a first step towards translating experimental findings suggesting that stochastic across-sample hyper-variability in the expression of specific genes is a stable and general property of cancer into predictive and diagnostic signatures. Using single-chip microarray normalization and quality assessment methods, we developed an anti-profile for colon cancer in tissue biopsy samples. To demonstrate the translational potential of our findings, we applied the signature developed in the tissue samples, without any further retraining or normalization, to screen patients for colon cancer based on genomic measurements from peripheral blood in an independent study (AUC of 0.89). This method achieved higher accuracy than the signature underlying commercially available peripheral blood screening tests for colon cancer (AUC of 0.81). We also confirmed the existence of hyper-variable genes across a range of cancer types and found that a significant proportion of tissue-specific genes are hyper-variable in cancer. Based on these observations, we developed a universal cancer anti-profile that accurately distinguishes cancer from normal regardless of tissue type (ten-fold cross-validation AUC > 0.92). CONCLUSIONS: We have introduced anti-profiles as a new approach for developing cancer genomic signatures that specifically takes advantage of gene expression heterogeneity. We have demonstrated that anti-profiles can be successfully applied to develop peripheral-blood based diagnostics for cancer and used anti-profiles to develop a highly accurate universal cancer signature. By using single-chip normalization and quality assessment methods, no further retraining of signatures developed by the anti-profile approach would be required before their application in clinical settings. Our results suggest that anti-profiles may be used to develop inexpensive and non-invasive universal cancer screening tests. VL - 13 N1 - http://www.ncbi.nlm.nih.gov/pubmed/23088656?dopt=Abstract ER - TY - JOUR T1 - Gene Prediction with Glimmer for Metagenomic Sequences Augmented by Classification and Clustering JF - Nucleic Acids ResearchNucl. Acids Res.Nucleic Acids ResearchNucl. Acids Res. Y1 - 2012 A1 - Kelley, David R. A1 - Liu, Bo A1 - Delcher, Arthur L. A1 - M. Pop A1 - Salzberg, Steven L. AB - Environmental shotgun sequencing (or metagenomics) is widely used to survey the communities of microbial organisms that live in many diverse ecosystems, such as the human body. Finding the protein-coding genes within the sequences is an important step for assessing the functional capacity of a metagenome. In this work, we developed a metagenomics gene prediction system Glimmer-MG that achieves significantly greater accuracy than previous systems via novel approaches to a number of important prediction subtasks. First, we introduce the use of phylogenetic classifications of the sequences to model parameterization. We also cluster the sequences, grouping together those that likely originated from the same organism. Analogous to iterative schemes that are useful for whole genomes, we retrain our models within each cluster on the initial gene predictions before making final predictions. Finally, we model both insertion/deletion and substitution sequencing errors using a different approach than previous software, allowing Glimmer-MG to change coding frame or pass through stop codons by predicting an error. In a comparison among multiple gene finding methods, Glimmer-MG makes the most sensitive and precise predictions on simulated and real metagenomes for all read lengths and error rates tested. VL - 40 SN - 0305-1048, 1362-4962 ER - TY - JOUR T1 - Genomic analysis of ICEVchBan8: An atypical genetic element in Vibrio cholerae JF - FEBS LettersFEBS Letters Y1 - 2012 A1 - Taviani, Elisa A1 - Spagnoletti, Matteo A1 - Ceccarelli, Daniela A1 - Haley, Bradd J. A1 - Hasan, Nur A. A1 - Chen, Arlene A1 - Colombo, Mauro M. A1 - Huq, Anwar A1 - Rita R. Colwell KW - Genomic islands KW - Integrative conjugative elements KW - Lateral gene transfer KW - Vibrio cholerae AB - Genomic islands (GIs) and integrative conjugative elements (ICEs) are major players in bacterial evolution since they encode genes involved in adaptive functions of medical or environmental importance. Here we performed the genomic analysis of ICEVchBan8, an unusual ICE found in the genome of a clinical non-toxigenic Vibrio cholerae O37 isolate. ICEVchBan8 shares most of its genetic structure with SXT/R391 ICEs. However, this ICE codes for a different integration/excision module is located at a different insertion site, and part of its genetic cargo shows homology to other pathogenicity islands of V. cholerae. SN - 0014-5793 ER - TY - JOUR T1 - Genomic analysis of sleep deprivation reveals translational regulation in the hippocampus JF - Physiological GenomicsPhysiological Genomics Y1 - 2012 A1 - Christopher, G. Vecsey A1 - Lucia, Peixoto A1 - Jennifer, H. K. Choi A1 - Mathieu, Wimmer A1 - Devan, Jaganath A1 - Pepe, J. Hernandez A1 - Jennifer, Blackwell A1 - Karuna, Meda A1 - Alan, J. Park A1 - Sridhar Hannenhalli A1 - Abel, Ted ER - TY - JOUR T1 - Genomic insights to SAR86, an abundant and uncultivated marine bacterial lineage. JF - ISME J Y1 - 2012 A1 - Dupont, Chris L A1 - Rusch, Douglas B A1 - Yooseph, Shibu A1 - Lombardo, Mary-Jane A1 - Richter, R Alexander A1 - Valas, Ruben A1 - Novotny, Mark A1 - Yee-Greenbaum, Joyclyn A1 - Selengut, Jeremy D A1 - Haft, Dan H A1 - Halpern, Aaron L A1 - Lasken, Roger S A1 - Nealson, Kenneth A1 - Friedman, Robert A1 - Venter, J Craig KW - Computational Biology KW - Gammaproteobacteria KW - Genome, Bacterial KW - Genomic Library KW - metagenomics KW - Oceans and Seas KW - Phylogeny KW - plankton KW - Rhodopsin KW - Rhodopsins, Microbial KW - RNA, Ribosomal, 16S KW - Seawater AB -

Bacteria in the 16S rRNA clade SAR86 are among the most abundant uncultivated constituents of microbial assemblages in the surface ocean for which little genomic information is currently available. Bioinformatic techniques were used to assemble two nearly complete genomes from marine metagenomes and single-cell sequencing provided two more partial genomes. Recruitment of metagenomic data shows that these SAR86 genomes substantially increase our knowledge of non-photosynthetic bacteria in the surface ocean. Phylogenomic analyses establish SAR86 as a basal and divergent lineage of γ-proteobacteria, and the individual genomes display a temperature-dependent distribution. Modestly sized at 1.25-1.7 Mbp, the SAR86 genomes lack several pathways for amino-acid and vitamin synthesis as well as sulfate reduction, trends commonly observed in other abundant marine microbes. SAR86 appears to be an aerobic chemoheterotroph with the potential for proteorhodopsin-based ATP generation, though the apparent lack of a retinal biosynthesis pathway may require it to scavenge exogenously-derived pigments to utilize proteorhodopsin. The genomes contain an expanded capacity for the degradation of lipids and carbohydrates acquired using a wealth of tonB-dependent outer membrane receptors. Like the abundant planktonic marine bacterial clade SAR11, SAR86 exhibits metabolic streamlining, but also a distinct carbon compound specialization, possibly avoiding competition.

VL - 6 CP - 6 M3 - 10.1038/ismej.2011.189 ER - TY - JOUR T1 - Genomic insights to SAR86, an abundant and uncultivated marine bacterial lineage JF - The ISME journalThe ISME journal Y1 - 2012 A1 - Dupont, Chris L. A1 - Rusch, Douglas B. A1 - Yooseph, Shibu A1 - Lombardo, Mary-Jane A1 - Richter, R. Alexander A1 - Valas, Ruben A1 - Novotny, Mark A1 - Yee-Greenbaum, Joyclyn A1 - J. Selengut A1 - Haft, Dan H. A1 - Halpern, Aaron L. A1 - Lasken, Roger S. A1 - Nealson, Kenneth A1 - Friedman, Robert A1 - Venter, J. Craig KW - Computational Biology KW - Gammaproteobacteria KW - Genome, Bacterial KW - Genomic Library KW - metagenomics KW - Oceans and Seas KW - Phylogeny KW - plankton KW - Rhodopsin KW - RNA, Ribosomal, 16S KW - Seawater AB - Bacteria in the 16S rRNA clade SAR86 are among the most abundant uncultivated constituents of microbial assemblages in the surface ocean for which little genomic information is currently available. Bioinformatic techniques were used to assemble two nearly complete genomes from marine metagenomes and single-cell sequencing provided two more partial genomes. Recruitment of metagenomic data shows that these SAR86 genomes substantially increase our knowledge of non-photosynthetic bacteria in the surface ocean. Phylogenomic analyses establish SAR86 as a basal and divergent lineage of γ-proteobacteria, and the individual genomes display a temperature-dependent distribution. Modestly sized at 1.25-1.7 Mbp, the SAR86 genomes lack several pathways for amino-acid and vitamin synthesis as well as sulfate reduction, trends commonly observed in other abundant marine microbes. SAR86 appears to be an aerobic chemoheterotroph with the potential for proteorhodopsin-based ATP generation, though the apparent lack of a retinal biosynthesis pathway may require it to scavenge exogenously-derived pigments to utilize proteorhodopsin. The genomes contain an expanded capacity for the degradation of lipids and carbohydrates acquired using a wealth of tonB-dependent outer membrane receptors. Like the abundant planktonic marine bacterial clade SAR11, SAR86 exhibits metabolic streamlining, but also a distinct carbon compound specialization, possibly avoiding competition. VL - 6 N1 - http://www.ncbi.nlm.nih.gov/pubmed/22170421?dopt=Abstract ER - TY - JOUR T1 - Global secretome analysis identifies novel mediators of bone metastasis. JF - Cell Res Y1 - 2012 A1 - Blanco, Mario Andres A1 - LeRoy, Gary A1 - Khan, Zia A1 - Alečković, Maša A1 - Zee, Barry M A1 - Garcia, Benjamin A A1 - Kang, Yibin KW - Animals KW - Biomarkers, Tumor KW - Bone Neoplasms KW - Cell Line, Tumor KW - Collagen Type VI KW - Computational Biology KW - HUMANS KW - Mass Spectrometry KW - Mice KW - Neoplasms KW - Plasminogen Activators KW - Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase KW - Proteome KW - proteomics KW - Salivary Cystatins AB -

Bone is the one of the most common sites of distant metastasis of solid tumors. Secreted proteins are known to influence pathological interactions between metastatic cancer cells and the bone stroma. To comprehensively profile secreted proteins associated with bone metastasis, we used quantitative and non-quantitative mass spectrometry to globally analyze the secretomes of nine cell lines of varying bone metastatic ability from multiple species and cancer types. By comparing the secretomes of parental cells and their bone metastatic derivatives, we identified the secreted proteins that were uniquely associated with bone metastasis in these cell lines. We then incorporated bioinformatic analyses of large clinical metastasis datasets to obtain a list of candidate novel bone metastasis proteins of several functional classes that were strongly associated with both clinical and experimental bone metastasis. Functional validation of selected proteins indicated that in vivo bone metastasis can be promoted by high expression of (1) the salivary cystatins CST1, CST2, and CST4; (2) the plasminogen activators PLAT and PLAU; or (3) the collagen functionality proteins PLOD2 and COL6A1. Overall, our study has uncovered several new secreted mediators of bone metastasis and therefore demonstrated that secretome analysis is a powerful method for identification of novel biomarkers and candidate therapeutic targets.

VL - 22 CP - 9 M3 - 10.1038/cr.2012.89 ER - TY - Generic T1 - Global secretome analysis identifies novel mediators of bone metastasis Y1 - 2012 A1 - Blanco, Mario Andres A1 - LeRoy, Gary A1 - Khan, Zia A1 - čković, ša A1 - Zee, Barry M A1 - Garcia, Benjamin A A1 - Kang, Yibin JA - Cell Research VL - 22 UR - http://www.nature.com/doifinder/10.1038/cr.2012.89 CP - 9 J1 - Cell Res M3 - 10.1038/cr.2012.89 ER - TY - JOUR T1 - Identification of Coli Surface Antigen 23, a Novel Adhesin of Enterotoxigenic Escherichia coli JF - Infection and immunityInfection and immunity Y1 - 2012 A1 - Del Canto, F. A1 - Botkin, D. J. A1 - Valenzuela, P. A1 - Popov, V. A1 - Ruiz-Perez, F. A1 - Nataro, J. P. A1 - Levine, M. M. A1 - Stine, O. C. A1 - M. Pop A1 - Torres, A. G. A1 - others, PB - American Society for Microbiology VL - 80 ER - TY - JOUR T1 - Inferring Evolution of Gene Duplicates Using Probabilistic Models and Nonparametric Belief Propagation JF - BMC GenomicsBMC Genomics Y1 - 2012 A1 - Jia, Zeng A1 - Sridhar Hannenhalli ER - TY - JOUR T1 - InterPro in 2011: new developments in the family and domain prediction database JF - Nucleic acids researchNucleic Acids Research Y1 - 2012 A1 - Hunter, Sarah A1 - Jones, Philip A1 - Mitchell, Alex A1 - Apweiler, Rolf A1 - Attwood, Teresa K. A1 - Bateman, Alex A1 - Bernard, Thomas A1 - Binns, David A1 - Bork, Peer A1 - Burge, Sarah A1 - de Castro, Edouard A1 - Coggill, Penny A1 - Corbett, Matthew A1 - Das, Ujjwal A1 - Daugherty, Louise A1 - Duquenne, Lauranne A1 - Finn, Robert D. A1 - Fraser, Matthew A1 - Gough, Julian A1 - Haft, Daniel A1 - Hulo, Nicolas A1 - Kahn, Daniel A1 - Kelly, Elizabeth A1 - Letunic, Ivica A1 - Lonsdale, David A1 - Lopez, Rodrigo A1 - Madera, Martin A1 - Maslen, John A1 - McAnulla, Craig A1 - McDowall, Jennifer A1 - McMenamin, Conor A1 - Mi, Huaiyu A1 - Mutowo-Muellenet, Prudence A1 - Mulder, Nicola A1 - Natale, Darren A1 - Orengo, Christine A1 - Pesseat, Sebastien A1 - Punta, Marco A1 - Quinn, Antony F. A1 - Rivoire, Catherine A1 - Sangrador-Vegas, Amaia A1 - J. Selengut A1 - Sigrist, Christian J. A. A1 - Scheremetjew, Maxim A1 - Tate, John A1 - Thimmajanarthanan, Manjulapramila A1 - Thomas, Paul D. A1 - Wu, Cathy H. A1 - Yeats, Corin A1 - Yong, Siew-Yit KW - Databases, Protein KW - Protein Structure, Tertiary KW - Proteins KW - Sequence Analysis, Protein KW - software KW - Terminology as Topic KW - User-Computer Interface AB - InterPro (http://www.ebi.ac.uk/interpro/) is a database that integrates diverse information about protein families, domains and functional sites, and makes it freely available to the public via Web-based interfaces and services. Central to the database are diagnostic models, known as signatures, against which protein sequences can be searched to determine their potential function. InterPro has utility in the large-scale analysis of whole genomes and meta-genomes, as well as in characterizing individual protein sequences. Herein we give an overview of new developments in the database and its associated software since 2009, including updates to database content, curation processes and Web and programmatic interfaces. VL - 40 N1 - http://www.ncbi.nlm.nih.gov/pubmed/22096229?dopt=Abstract ER - TY - JOUR T1 - InterPro in 2011: new developments in the family and domain prediction database. JF - Nucleic Acids Res Y1 - 2012 A1 - Hunter, Sarah A1 - Jones, Philip A1 - Mitchell, Alex A1 - Apweiler, Rolf A1 - Attwood, Teresa K A1 - Bateman, Alex A1 - Bernard, Thomas A1 - Binns, David A1 - Bork, Peer A1 - Burge, Sarah A1 - de Castro, Edouard A1 - Coggill, Penny A1 - Corbett, Matthew A1 - Das, Ujjwal A1 - Daugherty, Louise A1 - Duquenne, Lauranne A1 - Finn, Robert D A1 - Fraser, Matthew A1 - Gough, Julian A1 - Haft, Daniel A1 - Hulo, Nicolas A1 - Kahn, Daniel A1 - Kelly, Elizabeth A1 - Letunic, Ivica A1 - Lonsdale, David A1 - Lopez, Rodrigo A1 - Madera, Martin A1 - Maslen, John A1 - McAnulla, Craig A1 - McDowall, Jennifer A1 - McMenamin, Conor A1 - Mi, Huaiyu A1 - Mutowo-Muellenet, Prudence A1 - Mulder, Nicola A1 - Natale, Darren A1 - Orengo, Christine A1 - Pesseat, Sebastien A1 - Punta, Marco A1 - Quinn, Antony F A1 - Rivoire, Catherine A1 - Sangrador-Vegas, Amaia A1 - Selengut, Jeremy D A1 - Sigrist, Christian J A A1 - Scheremetjew, Maxim A1 - Tate, John A1 - Thimmajanarthanan, Manjulapramila A1 - Thomas, Paul D A1 - Wu, Cathy H A1 - Yeats, Corin A1 - Yong, Siew-Yit KW - Databases, Protein KW - Protein Structure, Tertiary KW - Proteins KW - Sequence Analysis, Protein KW - software KW - Terminology as Topic KW - User-Computer Interface AB -

InterPro (http://www.ebi.ac.uk/interpro/) is a database that integrates diverse information about protein families, domains and functional sites, and makes it freely available to the public via Web-based interfaces and services. Central to the database are diagnostic models, known as signatures, against which protein sequences can be searched to determine their potential function. InterPro has utility in the large-scale analysis of whole genomes and meta-genomes, as well as in characterizing individual protein sequences. Herein we give an overview of new developments in the database and its associated software since 2009, including updates to database content, curation processes and Web and programmatic interfaces.

VL - 40 CP - Database issue M3 - 10.1093/nar/gkr948 ER - TY - JOUR T1 - Irreconcilable differences: divorcing geographic mutation and recombination rates within a global MRSA clone JF - Genome Biology Y1 - 2012 A1 - Phillippy, Adam A1 - Todd Treangen VL - 13 ER - TY - JOUR T1 - A molecular phylogeny for the leaf-roller moths (Lepidoptera: Tortricidae) and its implications for classification and life history evolution. JF - PloS one Y1 - 2012 A1 - Regier, Jerome C A1 - Brown, John W A1 - Mitter, Charles A1 - Baixeras, Joaquin A1 - Cho, Soowon A1 - Michael P. Cummings A1 - Zwick, Andreas AB - Tortricidae, one of the largest families of microlepidopterans, comprise about 10,000 described species worldwide, including important pests, biological control agents and experimental models. Understanding of tortricid phylogeny, the basis for a predictive classification, is currently provisional. We present the first detailed molecular estimate of relationships across the tribes and subfamilies of Tortricidae, assess its concordance with previous morphological evidence, and re-examine postulated evolutionary trends in host plant use and biogeography. VL - 7 ER - TY - JOUR T1 - A molecular phylogeny for the pyraloid moths (Lepidoptera: Pyraloidea) and its implications for higher-level classification JF - Systematic Entomology Y1 - 2012 A1 - Regier, Jerome C. A1 - Mitter, Charles A1 - SOLIS, M. ALMA A1 - HAYDEN, JAMES E. A1 - LANDRY, BERNARD A1 - NUSS, MATTHIAS A1 - Simonsen, Thomas J. A1 - Yen, Shen-Horn A1 - Zwick, Andreas A1 - Michael P. Cummings VL - 37 UR - http://doi.wiley.com/10.1111/sen.2012.37.issue-4http://doi.wiley.com/10.1111/j.1365-3113.2012.00641.x CP - 4 M3 - 10.1111/sen.2012.37.issue-410.1111/j.1365-3113.2012.00641.x ER - TY - JOUR T1 - MrBayes 3.2: Efficient Bayesian Phylogenetic Inference and Model Choice Across a Large Model Space JF - Systematic Biology Y1 - 2012 A1 - F. Ronquist A1 - Teslenko, M. A1 - van der Mark, P. A1 - Ayres, D. L. A1 - Darling, A. A1 - Hohna, S. A1 - B. Larget A1 - Liu, L. A1 - Suchard, M. A. A1 - J. P. Huelsenbeck VL - 61 M3 - 10.1093/sysbio/sys029 ER - TY - JOUR T1 - Myocardin-like Protein (MKL)-2 Regulates TGF-beta Signaling JF - Embryonic Stem Cells and the Developing Vasculature DevelopmentEmbryonic Stem Cells and the Developing Vasculature Development Y1 - 2012 A1 - Li, Jian A1 - Nina, Bowens A1 - Lan, Cheng A1 - Mary, Chen A1 - Sridhar Hannenhalli A1 - Xiaohong, Zhu A1 - Thomas, P. Cappola A1 - Parmacek, Michael S. ER - TY - JOUR T1 - Occurrence of protozoans & their limnological relationships in some ponds of Mathbaria, Bangladesh JF - University Journal of Zoology, Rajshahi UniversityUniversity Journal of Zoology, Rajshahi University Y1 - 2012 A1 - Mozumder, P. K. A1 - Banu, M. A. A1 - Naser, M. N. A1 - Ali, M. S. A1 - Alam, M. A1 - Sack, R. B. A1 - Rita R. Colwell A1 - Huq, A. VL - 29 SN - 1023-6104 ER - TY - JOUR T1 - The partitioned LASSO-patternsearch algorithm with application to gene expression data JF - BMC bioinformaticsBMC Bioinformatics Y1 - 2012 A1 - Shi, Weiliang A1 - Wahba, Grace A1 - Irizarry, Rafael A. A1 - Héctor Corrada Bravo A1 - Wright, Stephen J. KW - algorithms KW - Breast Neoplasms KW - Computer simulation KW - Female KW - Gene expression KW - Gene Expression Profiling KW - Genomics KW - HUMANS KW - Models, Genetic AB - BACKGROUND: In systems biology, the task of reverse engineering gene pathways from data has been limited not just by the curse of dimensionality (the interaction space is huge) but also by systematic error in the data. The gene expression barcode reduces spurious association driven by batch effects and probe effects. The binary nature of the resulting expression calls lends itself perfectly to modern regularization approaches that thrive in high-dimensional settings. RESULTS: The Partitioned LASSO-Patternsearch algorithm is proposed to identify patterns of multiple dichotomous risk factors for outcomes of interest in genomic studies. A partitioning scheme is used to identify promising patterns by solving many LASSO-Patternsearch subproblems in parallel. All variables that survive this stage proceed to an aggregation stage where the most significant patterns are identified by solving a reduced LASSO-Patternsearch problem in just these variables. This approach was applied to genetic data sets with expression levels dichotomized by gene expression bar code. Most of the genes and second-order interactions thus selected and are known to be related to the outcomes. CONCLUSIONS: We demonstrate with simulations and data analyses that the proposed method not only selects variables and patterns more accurately, but also provides smaller models with better prediction accuracy, in comparison to several alternative methodologies. VL - 13 N1 - http://www.ncbi.nlm.nih.gov/pubmed/22587526?dopt=Abstract ER - TY - Generic T1 - Plasmodium falciparum merozoite surface protein 1 blocks the proinflammatory protein S100P. Y1 - 2012 A1 - Waisberg, Michael A1 - Cerqueira, Gustavo C A1 - Yager, Stephanie B A1 - Francischetti, Ivo M B A1 - Lu, Jinghua A1 - Gera, Nidhi A1 - Srinivasan, Prakash A1 - Miura, Kazutoyo A1 - Rada, Balazs A1 - Lukszo, Jan A1 - Barbian, Kent D A1 - Leto, Thomas L A1 - Porcella, Stephen F A1 - Narum, David L A1 - El-Sayed, Najib A1 - Miller, Louis H A1 - Pierce, Susan K KW - Amino Acid Sequence KW - Animals KW - Calcium-Binding Proteins KW - Chromatography, Gel KW - Electrophoresis, Polyacrylamide Gel KW - Enzyme-Linked Immunosorbent Assay KW - HUMANS KW - Merozoite Surface Protein 1 KW - Microscopy, Confocal KW - Molecular Sequence Data KW - Neoplasm Proteins KW - Plasmodium falciparum KW - Sequence Homology, Amino Acid KW - Surface Plasmon Resonance AB -

The malaria parasite, Plasmodium falciparum, and the human immune system have coevolved to ensure that the parasite is not eliminated and reinfection is not resisted. This relationship is likely mediated through a myriad of host-parasite interactions, although surprisingly few such interactions have been identified. Here we show that the 33-kDa fragment of P. falciparum merozoite surface protein 1 (MSP1(33)), an abundant protein that is shed during red blood cell invasion, binds to the proinflammatory protein, S100P. MSP1(33) blocks S100P-induced NFκB activation in monocytes and chemotaxis in neutrophils. Remarkably, S100P binds to both dimorphic alleles of MSP1, estimated to have diverged >27 Mya, suggesting an ancient, conserved relationship between these parasite and host proteins that may serve to attenuate potentially damaging inflammatory responses.

JA - Proc Natl Acad Sci U S A VL - 109 CP - 14 M3 - 10.1073/pnas.1202689109 ER - TY - JOUR T1 - Quantitative measurement of allele-specific protein expression in a diploid yeast hybrid by LC-MS JF - Molecular Systems Biology Y1 - 2012 A1 - Khan, Zia A1 - Bloom, Joshua S A1 - Amini, Sasan A1 - Singh, Mona A1 - Perlman, David H A1 - Caudy, Amy A A1 - Kruglyak, Leonid VL - 8 UR - http://msb.embopress.org/cgi/doi/10.1038/msb.2012.34 J1 - Mol Syst Biol M3 - 10.1038/msb.2012.34 ER - TY - Generic T1 - Quantitative measurement of allele-specific protein expression in a diploid yeast hybrid by LC-MS. Y1 - 2012 A1 - Khan, Zia A1 - Bloom, Joshua S A1 - Amini, Sasan A1 - Singh, Mona A1 - Perlman, David H A1 - Caudy, Amy A A1 - Kruglyak, Leonid KW - Alleles KW - Chromatography, Liquid KW - Fungal Proteins KW - Gene Expression Profiling KW - Gene Expression Regulation, Fungal KW - HUMANS KW - Mass Spectrometry KW - proteomics KW - Regression Analysis KW - Saccharomyces KW - Saccharomyces cerevisiae KW - Saccharomyces cerevisiae Proteins KW - Species Specificity AB -

Understanding the genetic basis of gene regulatory variation is a key goal of evolutionary and medical genetics. Regulatory variation can act in an allele-specific manner (cis-acting) or it can affect both alleles of a gene (trans-acting). Differential allele-specific expression (ASE), in which the expression of one allele differs from another in a diploid, implies the presence of cis-acting regulatory variation. While microarrays and high-throughput sequencing have enabled genome-wide measurements of transcriptional ASE, methods for measurement of protein ASE (pASE) have lagged far behind. We describe a flexible, accurate, and scalable strategy for measurement of pASE by liquid chromatography-coupled mass spectrometry (LC-MS). We apply this approach to a hybrid between the yeast species Saccharomyces cerevisiae and Saccharomyces bayanus. Our results provide the first analysis of the relative contribution of cis-acting and trans-acting regulatory differences to protein expression divergence between yeast species.

JA - Mol Syst Biol VL - 8 M3 - 10.1038/msb.2012.34 ER - TY - JOUR T1 - Role of Shrimp Chitin in the Ecology of Toxigenic Vibrio cholerae and Cholera Transmission JF - Frontiers in MicrobiologyFront MicrobiolFrontiers in MicrobiologyFront Microbiol Y1 - 2012 A1 - Nahar, Shamsun A1 - Sultana, Marzia A1 - Naser, M. Niamul A1 - Nair, Gopinath B. A1 - Watanabe, Haruo A1 - Ohnishi, Makoto A1 - Yamamoto, Shouji A1 - Endtz, Hubert A1 - Cravioto, Alejandro A1 - Sack, R. Bradley A1 - Hasan, Nur A. A1 - Sadique, Abdus A1 - Huq, Anwar A1 - Rita R. Colwell A1 - Alam, Munirul AB - Seasonal plankton blooms correlate with occurrence of cholera in Bangladesh, although the mechanism of how dormant Vibrio cholerae, enduring interepidemic period in biofilms and plankton, initiates seasonal cholera is not fully understood. In this study, laboratory microcosms prepared with estuarine Mathbaria water (MW) samples supported active growth of toxigenic V. cholerae O1 up to 7 weeks as opposed to 6 months when microcosms were supplemented with dehydrated shrimp chitin chips (CC) as the single source of nutrient. Bacterial counting and detection of wbe and ctxA genes were done employing culture, direct fluorescent antibody (DFA) assay, and multiplex-polymerase chain reaction methods. In MW microcosm, the aqueous phase became clear as the non-culturable cells settled, whereas the aqueous phase of the MW–CC microcosm became turbid from bacterial growth stimulated by chitin. Bacterial chitin degradation and biofilm formation proceeded from an initial steady state to a gradually declining bacterial culturable count. V. cholerae within the microenvironments of chitin and chitin-associated biofilms remained metabolically active even in a high acidic environment without losing either viability or virulence. It is concluded that the abundance of chitin that occurs during blooms plays an important role in the aquatic life cycle of V. cholerae and, ultimately, in the seasonal transmission of cholera. VL - 2 SN - 1664-302X ER - TY - JOUR T1 - Speeding Up Particle Trajectory Simulations under Moving Force Fields using GPUs JF - Journal of Computing and Information Science in EngineeringJournal of Computing and Information Science in Engineering Y1 - 2012 A1 - Patro, R. A1 - Dickerson, J. P. A1 - Bista, S. A1 - Gupta, S. K. A1 - Varshney, Amitabh AB - In this paper, we introduce a GPU-based framework forsimulating particle trajectories under both static and dynamic force fields. By exploiting the highly parallel nature of the problem and making efficient use of the available hardware, our simulator exhibits a significant speedup over its CPU- based analog. We apply our framework to a specific experi- mental simulation: the computation of trapping probabilities associated with micron-sized silica beads in optical trapping workbenches. When evaluating large numbers of trajectories (4096), we see approximately a 356 times speedup of the GPU-based simulator over its CPU-based counterpart. ER - TY - JOUR T1 - Structure, function and diversity of the healthy human microbiome JF - NatureNature Y1 - 2012 A1 - Huttenhower, C. A1 - Gevers, D. A1 - Knight, R. A1 - Abubucker, S. A1 - Badger, J. H. A1 - Chinwalla, A. T. A1 - Creasy, H. H. A1 - Earl, A. M. A1 - Fitzgerald, M. G. A1 - Fulton, R. S. A1 - others, VL - 486 ER - TY - JOUR T1 - Structure, function and diversity of the healthy human microbiome JF - Nature Y1 - 2012 A1 - Human Microbiome Project Consortium A1 - Todd Treangen VL - 486 ER - TY - JOUR T1 - Temporal and Spatial Variability in the Distribution of Vibrio vulnificus in the Chesapeake Bay: A Hindcast Study JF - EcoHealthEcoHealth Y1 - 2012 A1 - Banakar, V. A1 - Constantin de Magny, G. A1 - Jacobs, J. A1 - Murtugudde, R. A1 - Huq, A. A1 - J. Wood, R. A1 - Rita R. Colwell AB - Vibrio vulnificus, an estuarine bacterium, is the causative agent of seafood-related gastroenteritis, primary septicemia, and wound infections worldwide. It occurs as part of the normal microflora of coastal marine environments and can be isolated from water, sediment, and oysters. Hindcast prediction was undertaken to determine spatial and temporal variability in the likelihood of occurrence of V. vulnificus in surface waters of the Chesapeake Bay. Hindcast predictions were achieved by forcing a multivariate habitat suitability model with simulated sea surface temperature and salinity in the Bay for the period between 1991 and 2005 and the potential hotspots of occurrence of V. vulnificus in the Chesapeake Bay were identified. The likelihood of occurrence of V. vulnificus during high and low rainfall years was analyzed. From results of the study, it is concluded that hindcast prediction yields an improved understanding of environmental conditions associated with occurrence of V. vulnificus in the Chesapeake Bay. ER - TY - Generic T1 - Transcript expression analysis of putative Trypanosoma brucei GPI-anchored surface proteins during development in the tsetse and mammalian hosts. Y1 - 2012 A1 - Savage, Amy F A1 - Cerqueira, Gustavo C A1 - Regmi, Sandesh A1 - Wu, Yineng A1 - El Sayed, Najib M A1 - Aksoy, Serap KW - Animals KW - Computational Biology KW - Gastrointestinal Tract KW - Gene Expression Profiling KW - GPI-Linked Proteins KW - HUMANS KW - Male KW - Membrane Proteins KW - Protozoan Proteins KW - Real-Time Polymerase Chain Reaction KW - Salivary Glands KW - Trypanosoma brucei brucei KW - Trypanosomiasis, African KW - Tsetse Flies AB -

Human African Trypanosomiasis is a devastating disease caused by the parasite Trypanosoma brucei. Trypanosomes live extracellularly in both the tsetse fly and the mammal. Trypanosome surface proteins can directly interact with the host environment, allowing parasites to effectively establish and maintain infections. Glycosylphosphatidylinositol (GPI) anchoring is a common posttranslational modification associated with eukaryotic surface proteins. In T. brucei, three GPI-anchored major surface proteins have been identified: variant surface glycoproteins (VSGs), procyclic acidic repetitive protein (PARP or procyclins), and brucei alanine rich proteins (BARP). The objective of this study was to select genes encoding predicted GPI-anchored proteins with unknown function(s) from the T. brucei genome and characterize the expression profile of a subset during cyclical development in the tsetse and mammalian hosts. An initial in silico screen of putative T. brucei proteins by Big PI algorithm identified 163 predicted GPI-anchored proteins, 106 of which had no known functions. Application of a second GPI-anchor prediction algorithm (FragAnchor), signal peptide and trans-membrane domain prediction software resulted in the identification of 25 putative hypothetical proteins. Eighty-one gene products with hypothetical functions were analyzed for stage-regulated expression using semi-quantitative RT-PCR. The expression of most of these genes were found to be upregulated in trypanosomes infecting tsetse salivary gland and proventriculus tissues, and 38% were specifically expressed only by parasites infecting salivary gland tissues. Transcripts for all of the genes specifically expressed in salivary glands were also detected in mammalian infective metacyclic trypomastigotes, suggesting a possible role for these putative proteins in invasion and/or establishment processes in the mammalian host. These results represent the first large-scale report of the differential expression of unknown genes encoding predicted T. brucei surface proteins during the complete developmental cycle. This knowledge may form the foundation for the development of future novel transmission blocking strategies against metacyclic parasites.

JA - PLoS Negl Trop Dis VL - 6 CP - 6 M3 - 10.1371/journal.pntd.0001708 ER - TY - JOUR T1 - Vibrio Cholerae Classical Biotype Strains Reveal Distinct Signatures in Mexico JF - Journal of Clinical MicrobiologyJ. Clin. Microbiol.Journal of Clinical MicrobiologyJ. Clin. Microbiol. Y1 - 2012 A1 - Alam, Munirul A1 - Islam, M. Tarequl A1 - Rashed, Shah Manzur A1 - Johura, Fatema-Tuz A1 - Bhuiyan, Nurul A. A1 - Delgado, Gabriela A1 - Morales, Rosario A1 - Mendez, Jose Luis A1 - Navarro, Armando A1 - Watanabe, Haruo A1 - Hasan, Nur- A. A1 - Rita R. Colwell A1 - Cravioto, Alejandro AB - Vibrio cholerae O1 Classical (CL) biotype caused the 5th and 6th, and probably the earlier cholera pandemics, before the El Tor (ET) biotype initiated the 7th pandemic in Asia in the 1970's by completely displacing the CL biotype. Although the CL biotype was thought to be extinct in Asia, and it had never been reported from Latin America, V. cholerae CL and ET biotypes, including hybrid ET were found associated with endemic cholera in Mexico between 1991 and 1997. In this study, CL biotype strains isolated from endemic cholera in Mexico, between 1983 and 1997 were characterized in terms of major phenotypic and genetic traits, and compared with CL biotype strains isolated in Bangladesh between 1962 and 1989. According to sero- and bio-typing data, all V. cholerae strains tested had the major phenotypic and genotypic characteristics specific for the CL biotype. Antibiograms revealed the majority of the Bangladeshi strains to be resistant to trimethoprim/sulfamethoxazole, furazolidone, ampicillin, and gentamycin, while the Mexican strains were sensitive to all of these drugs, as well as to ciprofloxacin, erythromycin, and tetracycline. Pulsed-field gel electrophoresis (PFGE) of NotI-digested genomic DNA revealed characteristic banding patterns for all the CL biotype strains, although the Mexican strains differed with the Bangladeshi strains in 1-2 DNA bands. The difference may be subtle, but consistent, as confirmed by the sub-clustering patterns in the PFGE-based dendrogram, and can serve as regional signature, suggesting pre-1991 existence and evolution of the CL biotype strains in the Americas, independent from that of Asia. SN - 0095-1137, 1098-660X ER - TY - JOUR T1 - We are what we eat: how the diet of infants affects their gut microbiome JF - Genome BiologyGenome Biology Y1 - 2012 A1 - M. Pop PB - BioMed Central Ltd VL - 13 ER - TY - JOUR T1 - Whole genome analysis of Leptospira licerasiae provides insight into leptospiral evolution and pathogenicity JF - PLoS neglected tropical diseasesPLoS neglected tropical diseases Y1 - 2012 A1 - Ricaldi, Jessica N. A1 - Fouts, Derrick E. A1 - J. Selengut A1 - Harkins, Derek M. A1 - Patra, Kailash P. A1 - Moreno, Angelo A1 - Lehmann, Jason S. A1 - Purushe, Janaki A1 - Sanka, Ravi A1 - Torres, Michael A1 - Webster, Nicholas J. A1 - Vinetz, Joseph M. A1 - Matthias, Michael A. KW - DNA, Bacterial KW - Evolution, Molecular KW - Gene Transfer, Horizontal KW - Genome, Bacterial KW - Genomic islands KW - HUMANS KW - Leptospira KW - Molecular Sequence Data KW - Multigene Family KW - Prophages KW - Sequence Analysis, DNA KW - Virulence factors AB - The whole genome analysis of two strains of the first intermediately pathogenic leptospiral species to be sequenced (Leptospira licerasiae strains VAR010 and MMD0835) provides insight into their pathogenic potential and deepens our understanding of leptospiral evolution. Comparative analysis of eight leptospiral genomes shows the existence of a core leptospiral genome comprising 1547 genes and 452 conserved genes restricted to infectious species (including L. licerasiae) that are likely to be pathogenicity-related. Comparisons of the functional content of the genomes suggests that L. licerasiae retains several proteins related to nitrogen, amino acid and carbohydrate metabolism which might help to explain why these Leptospira grow well in artificial media compared with pathogenic species. L. licerasiae strains VAR010(T) and MMD0835 possess two prophage elements. While one element is circular and shares homology with LE1 of L. biflexa, the second is cryptic and homologous to a previously identified but unnamed region in L. interrogans serovars Copenhageni and Lai. We also report a unique O-antigen locus in L. licerasiae comprised of a 6-gene cluster that is unexpectedly short compared with L. interrogans in which analogous regions may include >90 such genes. Sequence homology searches suggest that these genes were acquired by lateral gene transfer (LGT). Furthermore, seven putative genomic islands ranging in size from 5 to 36 kb are present also suggestive of antecedent LGT. How Leptospira become naturally competent remains to be determined, but considering the phylogenetic origins of the genes comprising the O-antigen cluster and other putative laterally transferred genes, L. licerasiae must be able to exchange genetic material with non-invasive environmental bacteria. The data presented here demonstrate that L. licerasiae is genetically more closely related to pathogenic than to saprophytic Leptospira and provide insight into the genomic bases for its infectiousness and its unique antigenic characteristics. VL - 6 N1 - http://www.ncbi.nlm.nih.gov/pubmed/23145189?dopt=Abstract ER - TY - JOUR T1 - Whole genome analysis of Leptospira licerasiae provides insight into leptospiral evolution and pathogenicity. JF - PLoS Negl Trop Dis Y1 - 2012 A1 - Ricaldi, Jessica N A1 - Fouts, Derrick E A1 - Selengut, Jeremy D A1 - Harkins, Derek M A1 - Patra, Kailash P A1 - Moreno, Angelo A1 - Lehmann, Jason S A1 - Purushe, Janaki A1 - Sanka, Ravi A1 - Torres, Michael A1 - Webster, Nicholas J A1 - Vinetz, Joseph M A1 - Matthias, Michael A KW - DNA, Bacterial KW - Evolution, Molecular KW - Gene Transfer, Horizontal KW - Genome, Bacterial KW - Genomic islands KW - HUMANS KW - Leptospira KW - Molecular Sequence Data KW - Multigene Family KW - Prophages KW - Sequence Analysis, DNA KW - Virulence factors AB -

The whole genome analysis of two strains of the first intermediately pathogenic leptospiral species to be sequenced (Leptospira licerasiae strains VAR010 and MMD0835) provides insight into their pathogenic potential and deepens our understanding of leptospiral evolution. Comparative analysis of eight leptospiral genomes shows the existence of a core leptospiral genome comprising 1547 genes and 452 conserved genes restricted to infectious species (including L. licerasiae) that are likely to be pathogenicity-related. Comparisons of the functional content of the genomes suggests that L. licerasiae retains several proteins related to nitrogen, amino acid and carbohydrate metabolism which might help to explain why these Leptospira grow well in artificial media compared with pathogenic species. L. licerasiae strains VAR010(T) and MMD0835 possess two prophage elements. While one element is circular and shares homology with LE1 of L. biflexa, the second is cryptic and homologous to a previously identified but unnamed region in L. interrogans serovars Copenhageni and Lai. We also report a unique O-antigen locus in L. licerasiae comprised of a 6-gene cluster that is unexpectedly short compared with L. interrogans in which analogous regions may include >90 such genes. Sequence homology searches suggest that these genes were acquired by lateral gene transfer (LGT). Furthermore, seven putative genomic islands ranging in size from 5 to 36 kb are present also suggestive of antecedent LGT. How Leptospira become naturally competent remains to be determined, but considering the phylogenetic origins of the genes comprising the O-antigen cluster and other putative laterally transferred genes, L. licerasiae must be able to exchange genetic material with non-invasive environmental bacteria. The data presented here demonstrate that L. licerasiae is genetically more closely related to pathogenic than to saprophytic Leptospira and provide insight into the genomic bases for its infectiousness and its unique antigenic characteristics.

VL - 6 CP - 10 M3 - 10.1371/journal.pntd.0001853 ER - TY - JOUR T1 - Widespread evidence of viral miRNAs targeting host pathways JF - BMC GenomicsBMC Genomics Y1 - 2012 A1 - Joseph Carl, Joanne Trgovcich A1 - Sridhar Hannenhalli ER - TY - JOUR T1 - Accelerated evolution of 3'avian FOXE1 genes, and thyroid and feather specific expression of chicken FoxE1 JF - BMC Evolutionary BiologyBMC Evolutionary Biology Y1 - 2011 A1 - Yaklichkin, Sergey Yu A1 - Darnell, Diana K. A1 - Pier, Maricela V. A1 - Antin, Parker B. A1 - Sridhar Hannenhalli AB - The forkhead transcription factor gene E1 (FOXE1) plays an important role in regulation of thyroid development, palate formation and hair morphogenesis in mammals. However, avian FOXE1 genes have not been characterized and as such, codon evolution of FOXE1 orthologs in a broader evolutionary context of mammals and birds is not known. VL - 11 SN - 1471-2148 ER - TY - JOUR T1 - Accurate and fast estimation of taxonomic profiles from metagenomic shotgun sequences JF - BMC GenomicsBMC Genomics Y1 - 2011 A1 - Liu, Bo A1 - Gibbons, Theodore A1 - Ghodsi, Mohammad A1 - Todd Treangen A1 - M. Pop AB - A major goal of metagenomics is to characterize the microbial composition of an environment. The most popular approach relies on 16S rRNA sequencing, however this approach can generate biased estimates due to differences in the copy number of the gene between even closely related organisms, and due to PCR artifacts. The taxonomic composition can also be determined from metagenomic shotgun sequencing data by matching individual reads against a database of reference sequences. One major limitation of prior computational methods used for this purpose is the use of a universal classification threshold for all genes at all taxonomic levels. VL - 12 SN - 1471-2164 ER - TY - Generic T1 - Accurate proteome-wide protein quantification from high-resolution 15N mass spectra Y1 - 2011 A1 - Khan, Zia A1 - Amini, Sasan A1 - Bloom, Joshua S A1 - Ruse, Cristian A1 - Caudy, Amy A A1 - Kruglyak, Leonid A1 - Singh, Mona A1 - Perlman, David H A1 - Tavazoie, Saeed JA - Genome Biology VL - 12 UR - http://genomebiology.com/2012/12/12/R122 CP - 12 J1 - Genome BiolGenome Biology M3 - 10.1186/gb-2011-12-12-r122 ER - TY - JOUR T1 - Accurate proteome-wide protein quantification from high-resolution 15N mass spectra. JF - Genome Biol Y1 - 2011 A1 - Khan, Zia A1 - Amini, Sasan A1 - Bloom, Joshua S A1 - Ruse, Cristian A1 - Caudy, Amy A A1 - Kruglyak, Leonid A1 - Singh, Mona A1 - Perlman, David H A1 - Tavazoie, Saeed KW - algorithms KW - Amino Acid Sequence KW - Bacterial Proteins KW - Escherichia coli KW - Isotope Labeling KW - Mass Spectrometry KW - Molecular Sequence Data KW - Nitrogen Isotopes KW - Proteome KW - proteomics KW - Sensitivity and Specificity KW - software AB -

In quantitative mass spectrometry-based proteomics, the metabolic incorporation of a single source of 15N-labeled nitrogen has many advantages over using stable isotope-labeled amino acids. However, the lack of a robust computational framework for analyzing the resulting spectra has impeded wide use of this approach. We have addressed this challenge by introducing a new computational methodology for analyzing 15N spectra in which quantification is integrated with identification. Application of this method to an Escherichia coli growth transition reveals significant improvement in quantification accuracy over previous methods.

VL - 12 CP - 12 M3 - 10.1186/gb-2011-12-12-r122 ER - TY - JOUR T1 - Aquatic Realm and Cholera JF - Epidemiological and Molecular Aspects on CholeraEpidemiological and Molecular Aspects on Cholera Y1 - 2011 A1 - Huq, A. A1 - Grim, C. J. A1 - Rita R. Colwell AB - Cholera is an ancient disease that can be severe and life threatening. It occurs predominantly in areas of the world where populations lack safe drinking water. Epidemics of cholera are linked with malnutrition, poor sanitation, and conditions resulting from natural disasters such as severe flooding. According to a report published by WHO in 2000 [1], cholera remains a major public health problem and is becoming increasingly important since the number of countries in which cholera is endemic continues to increase. Unfortunately, outbreaks of the disease continue into the twenty-first century with ominous portent in the wake of global climate change [1]. Yet cholera is a preventable disease if people have access to safe drinking water and are properly educated how to protect themselves from the risk of infection with vibrios. Cholera also is an easily treatable disease. Oral rehydration therapy, a solution containing glucose and appropriate salts, has proven to be effective for treatment of most cholera victims [2]. Nevertheless, each year, tens of thousands of people are victims of the disease, bringing this “curse of humankind” to modern civilization. Present understanding of cholera is based on studies conducted over the past three decades and significant new information has been gained concerning environmental factors associated with this disease, especially how to detect the bacterium and where it lives in the natural environment, outside the human gut, and what triggers the annual outbreaks that occur with remarkable regularity. Environmental research on Vibrio cholerae and cholera has provided insights for prediction and prevention of the disease it causes, while the race for effective vaccines against cholera continues. ER - TY - JOUR T1 - Assessing the benefits of using mate-pairs to resolve repeats in de novo short-read prokaryotic assemblies JF - BMC bioinformaticsBMC Bioinformatics Y1 - 2011 A1 - Wetzel, J. A1 - Kingsford, Carl A1 - M. Pop PB - BioMed Central Ltd VL - 12 ER - TY - JOUR T1 - Bacillus anthracis comparative genome analysis in support of the Amerithrax investigation JF - Proceedings of the National Academy of SciencesProceedings of the National Academy of Sciences Y1 - 2011 A1 - Rasko, D. A. A1 - Worsham, P. L. A1 - Abshire, T. G. A1 - Stanley, S. T. A1 - Bannan, J. D. A1 - Wilson, M. R. A1 - Langham, R. J. A1 - Decker, R. S. A1 - Jiang, L. A1 - Read, T. D. A1 - others, PB - National Acad Sciences VL - 108 ER - TY - JOUR T1 - Bambus 2: Scaffolding Metagenomes JF - Bioinformatics Y1 - 2011 A1 - Koren, Sergey A1 - Todd Treangen A1 - M. Pop AB - Motivation: Sequencing projects increasingly target samples from non-clonal sources. In particular, metagenomics has enabled scientists to begin to characterize the structure of microbial communities. The software tools developed for assembling and analyzing sequencing data for clonal organisms are, however, unable to adequately process data derived from non-clonal sources.Results: We present a new scaffolder, Bambus 2, to address some of the challenges encountered when analyzing metagenomes. Our approach relies on a combination of a novel method for detecting genomic repeats and algorithms that analyze assembly graphs to identify biologically meaningful genomic variants. We compare our software to current assemblers using simulated and real data. We demonstrate that the repeat detection algorithms have higher sensitivity than current approaches without sacrificing specificity. In metagenomic datasets, the scaffolder avoids false joins between distantly related organisms while obtaining long-range contiguity. Bambus 2 represents a first step toward automated metagenomic assembly. Availability: Bambus 2 is open source and available from http://amos.sf.net. Contact: mpop@umiacs.umd.edu Supplementary Information: Supplementary data are available at Bioinformatics online. VL - 27 SN - 1367-4803, 1460-2059 ER - TY - JOUR T1 - Can Deliberately Incomplete Gene Sample Augmentation Improve a Phylogeny Estimate for the Advanced Moths and Butterflies (Hexapoda: Lepidoptera)? JF - Systematic BiologySyst BiolSystematic BiologySyst Biol Y1 - 2011 A1 - Cho, Soowon A1 - Zwick, Andreas A1 - Regier, Jerome C. A1 - Mitter, Charles A1 - Michael P. Cummings A1 - Yao, Jianxiu A1 - Du, Zaile A1 - Zhao, Hong A1 - Kawahara, Akito Y. A1 - Weller, Susan A1 - Davis, Donald R. A1 - Baixeras, Joaquin A1 - Brown, John W. A1 - Parr, Cynthia KW - Ditrysia KW - gene sampling KW - Hexapoda KW - Lepidoptera KW - missing data KW - molecular phylogenetics KW - nuclear genes KW - taxon sampling AB - This paper addresses the question of whether one can economically improve the robustness of a molecular phylogeny estimate by increasing gene sampling in only a subset of taxa, without having the analysis invalidated by artifacts arising from large blocks of missing data. Our case study stems from an ongoing effort to resolve poorly understood deeper relationships in the large clade Ditrysia ( > 150,000 species) of the insect order Lepidoptera (butterflies and moths). Seeking to remedy the overall weak support for deeper divergences in an initial study based on five nuclear genes (6.6 kb) in 123 exemplars, we nearly tripled the total gene sample (to 26 genes, 18.4 kb) but only in a third (41) of the taxa. The resulting partially augmented data matrix (45% intentionally missing data) consistently increased bootstrap support for groupings previously identified in the five-gene (nearly) complete matrix, while introducing no contradictory groupings of the kind that missing data have been predicted to produce. Our results add to growing evidence that data sets differing substantially in gene and taxon sampling can often be safely and profitably combined. The strongest overall support for nodes above the family level came from including all nucleotide changes, while partitioning sites into sets undergoing mostly nonsynonymous versus mostly synonymous change. In contrast, support for the deepest node for which any persuasive molecular evidence has yet emerged (78–85% bootstrap) was weak or nonexistent unless synonymous change was entirely excluded, a result plausibly attributed to compositional heterogeneity. This node (Gelechioidea + Apoditrysia), tentatively proposed by previous authors on the basis of four morphological synapomorphies, is the first major subset of ditrysian superfamilies to receive strong statistical support in any phylogenetic study. A “more-genes-only” data set (41 taxa×26 genes) also gave strong signal for a second deep grouping (Macrolepidoptera) that was obscured, but not strongly contradicted, in more taxon-rich analyses. VL - 60 SN - 1063-5157, 1076-836X ER - TY - JOUR T1 - Clonal transmission, dual peak, and off-season cholera in Bangladesh JF - Infection Ecology & EpidemiologyInfection Ecology & Epidemiology Y1 - 2011 A1 - Alam, M. A1 - Islam, A. A1 - Bhuiyan, N. A. A1 - Rahim, N. A1 - Hossain, A. A1 - Khan, G. Y. A1 - Ahmed, D. A1 - Watanabe, H. A1 - Izumiya, H. A1 - Faruque, A. S. G. A1 - Rita R. Colwell VL - 1 ER - TY - JOUR T1 - Complete Columbian mammoth mitogenome suggests interbreeding with woolly mammoths JF - Genome biology Y1 - 2011 A1 - Enk, Jacob A1 - Devault, Alison A1 - Debruyne, Regis A1 - King, Christine E A1 - Todd Treangen A1 - O'Rourke, Dennis A1 - Salzberg, Steven L A1 - Fisher, Daniel A1 - MacPhee, Ross A1 - Poinar, Hendrik VL - 12 ER - TY - JOUR T1 - A computational statistics approach for estimating the spatial range of morphogen gradients. JF - Development Y1 - 2011 A1 - Kanodia, Jitendra S A1 - Kim, Yoosik A1 - Tomer, Raju A1 - Khan, Zia A1 - Chung, Kwanghun A1 - Storey, John D A1 - Lu, Hang A1 - Keller, Philipp J A1 - Shvartsman, Stanislav Y KW - Animals KW - Biostatistics KW - Cleavage Stage, Ovum KW - Computational Biology KW - Computer simulation KW - Drosophila KW - Drosophila Proteins KW - Embryo, Nonmammalian KW - Gene Expression Regulation, Developmental KW - Genes, Developmental KW - Imaging, Three-Dimensional KW - In Situ Hybridization, Fluorescence KW - Morphogenesis KW - Osmolar Concentration KW - Tissue Distribution AB -

A crucial issue in studies of morphogen gradients relates to their range: the distance over which they can act as direct regulators of cell signaling, gene expression and cell differentiation. To address this, we present a straightforward statistical framework that can be used in multiple developmental systems. We illustrate the developed approach by providing a point estimate and confidence interval for the spatial range of the graded distribution of nuclear Dorsal, a transcription factor that controls the dorsoventral pattern of the Drosophila embryo.

VL - 138 CP - 22 M3 - 10.1242/dev.071571 ER - TY - Generic T1 - A computational statistics approach for estimating the spatial range of morphogen gradients Y1 - 2011 A1 - Kanodia, J. S. A1 - Kim, Y. A1 - Tomer, R. A1 - Khan, Z. A1 - Chung, K. A1 - Storey, J. D. A1 - Lu, H. A1 - Keller, P. J. A1 - Shvartsman, S. Y. JA - Development VL - 138 UR - http://dev.biologists.org/cgi/doi/10.1242/dev.071571 CP - 22 J1 - Development M3 - 10.1242/dev.071571 ER - TY - Generic T1 - Computing the Tree of Life: Leveraging the Power of Desktop and Service Grids T2 - Parallel and Distributed Processing Workshops and Phd Forum (IPDPSW), 2011 IEEE International Symposium on Y1 - 2011 A1 - Adam L. Bazinet A1 - Michael P. Cummings KW - (artificial KW - (mathematics) KW - analysis KW - BOINC KW - COMPUTATION KW - computational KW - computing KW - data KW - Estimation KW - evolutionary KW - GARLI KW - genetic KW - Grid KW - GRIDS KW - handling KW - heterogeneous KW - History KW - HPC KW - information KW - intelligence) KW - interface KW - interfaces KW - Internet KW - jobs KW - lattice KW - learning KW - life KW - likelihood KW - load KW - machine KW - maximum KW - method KW - model KW - molecular KW - phylogenetic KW - portal KW - Portals KW - power KW - project KW - resource KW - Science KW - sequence KW - service KW - services KW - sets KW - software KW - substantial KW - system KW - systematics KW - tree KW - TREES KW - user KW - Web AB - The trend in life sciences research, particularly in molecular evolutionary systematics, is toward larger data sets and ever-more detailed evolutionary models, which can generate substantial computational loads. Over the past several years we have developed a grid computing system aimed at providing researchers the computational power needed to complete such analyses in a timely manner. Our grid system, known as The Lattice Project, was the first to combine two models of grid computing - the service model, which mainly federates large institutional HPC resources, and the desktop model, which harnesses the power of PCs volunteered by the general public. Recently we have developed a "science portal" style web interface that makes it easier than ever for phylogenetic analyses to be completed using GARLI, a popular program that uses a maximum likelihood method to infer the evolutionary history of organisms on the basis of genetic sequence data. This paper describes our approach to scheduling thousands of GARLI jobs with diverse requirements to heterogeneous grid resources, which include volunteer computers running BOINC software. A key component of this system provides a priori GARLI runtime estimates using machine learning with random forests. JA - Parallel and Distributed Processing Workshops and Phd Forum (IPDPSW), 2011 IEEE International Symposium on ER - TY - JOUR T1 - A cost-aggregating integer linear program for motif finding JF - Journal of Discrete AlgorithmsJournal of Discrete Algorithms Y1 - 2011 A1 - Kingsford, Carl A1 - Zaslavsky, Elena A1 - Singh, Mona KW - Computational Biology KW - Integer linear programming KW - Sequence motif finding AB - In the motif finding problem one seeks a set of mutually similar substrings within a collection of biological sequences. This is an important and widely-studied problem, as such shared motifs in DNA often correspond to regulatory elements. We study a combinatorial framework where the goal is to find substrings of a given length such that the sum of their pairwise distances is minimized. We describe a novel integer linear program for the problem, which uses the fact that distances between substrings come from a limited set of possibilities allowing for aggregate consideration of sequence position pairs with the same distances. We show how to tighten its linear programming relaxation by adding an exponential set of constraints and give an efficient separation algorithm that can find violated constraints, thereby showing that the tightened linear program can still be solved in polynomial time. We apply our approach to find optimal solutions for the motif finding problem and show that it is effective in practice in uncovering known transcription factor binding sites. VL - 9 SN - 1570-8667 ER - TY - Generic T1 - Direct targeting of Sec23a by miR-200s influences cancer cell secretome and promotes metastatic colonization Y1 - 2011 A1 - Korpal, Manav A1 - Ell, Brian J A1 - Buffa, Francesca M A1 - Ibrahim, Toni A1 - Blanco, Mario A A1 - à-Terrassa, Toni A1 - Mercatali, Laura A1 - Khan, Zia A1 - Goodarzi, Hani A1 - Hua, Yuling A1 - Wei, Yong A1 - Hu, Guohong A1 - Garcia, Benjamin A A1 - Ragoussis, Jiannis A1 - Amadori, Dino A1 - Harris, Adrian L A1 - Kang, Yibin JA - Nature Medicine VL - 17 UR - http://www.nature.com/doifinder/10.1038/nm.2401 CP - 9 J1 - Nat Med M3 - 10.1038/nm.2401 ER - TY - JOUR T1 - Direct targeting of Sec23a by miR-200s influences cancer cell secretome and promotes metastatic colonization. JF - Nat Med Y1 - 2011 A1 - Korpal, Manav A1 - Ell, Brian J A1 - Buffa, Francesca M A1 - Ibrahim, Toni A1 - Blanco, Mario A A1 - Celià-Terrassa, Toni A1 - Mercatali, Laura A1 - Khan, Zia A1 - Goodarzi, Hani A1 - Hua, Yuling A1 - Wei, Yong A1 - Hu, Guohong A1 - Garcia, Benjamin A A1 - Ragoussis, Jiannis A1 - Amadori, Dino A1 - Harris, Adrian L A1 - Kang, Yibin KW - Animals KW - Cadherins KW - Cell Line, Tumor KW - Female KW - Gene Expression Profiling KW - Gene Expression Regulation, Neoplastic KW - HUMANS KW - Mass Spectrometry KW - Mice KW - Mice, Inbred BALB C KW - Microarray Analysis KW - MicroRNAs KW - Neoplasm Metastasis KW - Statistics, Nonparametric KW - Vesicular Transport Proteins AB -

Although the role of miR-200s in regulating E-cadherin expression and epithelial-to-mesenchymal transition is well established, their influence on metastatic colonization remains controversial. Here we have used clinical and experimental models of breast cancer metastasis to discover a pro-metastatic role of miR-200s that goes beyond their regulation of E-cadherin and epithelial phenotype. Overexpression of miR-200s is associated with increased risk of metastasis in breast cancer and promotes metastatic colonization in mouse models, phenotypes that cannot be recapitulated by E-cadherin expression alone. Genomic and proteomic analyses revealed global shifts in gene expression upon miR-200 overexpression toward that of highly metastatic cells. miR-200s promote metastatic colonization partly through direct targeting of Sec23a, which mediates secretion of metastasis-suppressive proteins, including Igfbp4 and Tinagl1, as validated by functional and clinical correlation studies. Overall, these findings suggest a pleiotropic role of miR-200s in promoting metastatic colonization by influencing E-cadherin-dependent epithelial traits and Sec23a-mediated tumor cell secretome.

VL - 17 CP - 9 M3 - 10.1038/nm.2401 ER - TY - JOUR T1 - DNACLUST: accurate and efficient clustering of phylogenetic marker genes JF - BMC BioinformaticsBMC Bioinformatics Y1 - 2011 A1 - Ghodsi, Mohammadreza A1 - Liu, Bo A1 - M. Pop AB - Clustering is a fundamental operation in the analysis of biological sequence data. New DNA sequencing technologies have dramatically increased the rate at which we can generate data, resulting in datasets that cannot be efficiently analyzed by traditional clustering methods. VL - 12 SN - 1471-2105 ER - TY - JOUR T1 - Effective detection of rare variants in pooled DNA samples using Cross-pool tailcurve analysis JF - Genome Biology Y1 - 2011 A1 - Niranjan, Tejasvi S A1 - Adamczyk, Abby A1 - Bravo, Hector A1 - Taub, Margaret A A1 - Wheelan, Sarah J A1 - Irizarry, Rafael A1 - Wang, Tao VL - 12 UR - http://genomebiology.biomedcentral.com/articles/10.1186/gb-2011-12-9-r93 CP - 9 J1 - Genome BiolGenome Biology M3 - 10.1186/gb-2011-12-9-r93 ER - TY - JOUR T1 - Epigenomic and RNA structural correlates of polyadenylation JF - RNA biologyRNA biology Y1 - 2011 A1 - Khaladkar, M. A1 - Smyda, M. A1 - Sridhar Hannenhalli PB - Landes Bioscience VL - 8 ER - TY - JOUR T1 - Extracting Between-Pathway Models from E-MAP Interactions Using Expected Graph Compression JF - Journal of Computational BiologyJournal of Computational Biology Y1 - 2011 A1 - Kelley, D. R. A1 - Kingsford, Carl VL - 18 ER - TY - JOUR T1 - Gene Coexpression Network Topology of Cardiac Development, Hypertrophy, and FailureClinical Perspective JF - Circulation: cardiovascular geneticsCirculation: Cardiovascular Genetics Y1 - 2011 A1 - Dewey, F. E. A1 - Perez, M. V. A1 - Wheeler, M. T. A1 - Watt, C. A1 - Spin, J. A1 - Langfelder, P. A1 - Horvath, S. A1 - Sridhar Hannenhalli A1 - Cappola, T. P. A1 - Ashley, E. A. PB - Lippincott Williams & Wilkins VL - 4 ER - TY - JOUR T1 - The genome and its implications. JF - Adv Parasitol Y1 - 2011 A1 - Teixeira, Santuza M A1 - El-Sayed, Najib M A1 - Araújo, Patrícia R KW - Animals KW - Antigens, Protozoan KW - Chagas Disease KW - Chromosomes KW - Comparative Genomic Hybridization KW - DNA, Protozoan KW - Gene Expression Regulation KW - Genetic Variation KW - Genome, Protozoan KW - Host-Parasite Interactions KW - HUMANS KW - Species Specificity KW - Synteny KW - Transcription, Genetic KW - Transfection KW - Trypanosoma cruzi AB -

Trypanosoma cruzi has a heterogeneous population composed of a pool of strains that circulate in the domestic and sylvatic cycles. Genome sequencing of the clone CL Brener revealed a highly repetitive genome of about 110Mb containing an estimated 22,570 genes. Because of its hybrid nature, sequences representing the two haplotypes have been generated. In addition, a repeat content close to 50% made the assembly of the estimated 41 pairs of chromosomes quite challenging. Similar to other trypanosomatids, the organization of T. cruzi chromosomes was found to be very peculiar, with protein-coding genes organized in long polycistronic transcription units encoding 20 or more proteins in one strand separated by strand switch regions. Another remarkable feature of the T. cruzi genome is the massive expansion of surface protein gene families. Because of the high genetic diversity of the T. cruzi population, sequencing of additional strains and comparative genomic and transcriptome analyses are in progress. Five years after its publication, the genome data have proven to be an essential tool for the study of T. cruzi and increasing efforts to translate this knowledge into the development of new modes of intervention to control Chagas disease are underway.

VL - 75 M3 - 10.1016/B978-0-12-385863-4.00010-1 ER - TY - JOUR T1 - Genome-Wide Survey of Natural Selection on Functional, Structural, and Network Properties of Polymorphic Sites in Saccharomyces Paradoxus JF - Molecular Biology and EvolutionMol Biol EvolMolecular Biology and EvolutionMol Biol Evol Y1 - 2011 A1 - Vishnoi, Anchal A1 - Sethupathy, Praveen A1 - Simola, Daniel A1 - Plotkin, Joshua B. A1 - Sridhar Hannenhalli KW - derived allele frequency KW - Evolution KW - natural selection KW - yeast AB - Background. To characterize the genetic basis of phenotypic evolution, numerous studies have identified individual genes that have likely evolved under natural selection. However, phenotypic changes may represent the cumulative effect of similar evolutionary forces acting on functionally related groups of genes. Phylogenetic analyses of divergent yeast species have identified functional groups of genes that have evolved at significantly different rates, suggestive of differential selection on the functional properties. However, due to environmental heterogeneity over long evolutionary timescales, selection operating within a single lineage may be dramatically different, and it is not detectable via interspecific comparisons alone. Moreover, interspecific studies typically quantify selection on protein-coding regions using the Dn/Ds ratio, which cannot be extended easily to study selection on noncoding regions or synonymous sites. The population genetic-based analysis of selection operating within a single lineage ameliorates these limitations. Findings. We investigated selection on several properties associated with genes, promoters, or polymorphic sites, by analyzing the derived allele frequency spectrum of single nucleotide polymorphisms (SNPs) in 28 strains of Saccharomyces paradoxus. We found evidence for significant differential selection between many functionally relevant categories of SNPs, underscoring the utility of function-centric approaches for discovering signatures of natural selection. When comparable, our findings are largely consistent with previous studies based on interspecific comparisons, with one notable exception: our study finds that mutations from an ancient amino acid to a relatively new amino acid are selectively disfavored, whereas interspecific comparisons have found selection against ancient amino acids. Several of our findings have not been addressed through prior interspecific studies: we find that synonymous mutations from preferred to unpreferred codons are selected against and that synonymous SNPs in the linker regions of proteins are relatively less constrained than those within protein domains. Conclusions. We present the first global survey of selection acting on various functional properties in S. paradoxus. We found that selection pressures previously detected over long evolutionary timescales have also shaped the evolution of S. paradoxus. Importantly, we also make novel discoveries untenable via conventional interspecific analyses. VL - 28 SN - 0737-4038, 1537-1719 ER - TY - JOUR T1 - Haem oxygenase is synthetically lethal with the tumour suppressor fumarate hydratase. JF - Nature Y1 - 2011 A1 - Frezza, Christian A1 - Zheng, Liang A1 - Folger, Ori A1 - Rajagopalan, Kartik N A1 - MacKenzie, Elaine D A1 - Jerby, Livnat A1 - Micaroni, Massimo A1 - Chaneton, Barbara A1 - Adam, Julie A1 - Hedley, Ann A1 - Kalna, Gabriela A1 - Tomlinson, Ian P M A1 - Pollard, Patrick J A1 - Watson, Dave G A1 - Deberardinis, Ralph J A1 - Shlomi, Tomer A1 - Ruppin, Eytan A1 - Gottlieb, Eyal KW - Animals KW - Bilirubin KW - Cell Line KW - Cells, Cultured KW - Citric Acid Cycle KW - Computer simulation KW - Fumarate Hydratase KW - Fumarates KW - Genes, Lethal KW - Genes, Tumor Suppressor KW - Glutamine KW - Heme KW - Heme Oxygenase (Decyclizing) KW - Kidney Neoplasms KW - Leiomyomatosis KW - Mice KW - Mitochondria KW - Mutation KW - NAD KW - Neoplastic Syndromes, Hereditary KW - Skin Neoplasms KW - Uterine Neoplasms AB -

Fumarate hydratase (FH) is an enzyme of the tricarboxylic acid cycle (TCA cycle) that catalyses the hydration of fumarate into malate. Germline mutations of FH are responsible for hereditary leiomyomatosis and renal-cell cancer (HLRCC). It has previously been demonstrated that the absence of FH leads to the accumulation of fumarate, which activates hypoxia-inducible factors (HIFs) at normal oxygen tensions. However, so far no mechanism that explains the ability of cells to survive without a functional TCA cycle has been provided. Here we use newly characterized genetically modified kidney mouse cells in which Fh1 has been deleted, and apply a newly developed computer model of the metabolism of these cells to predict and experimentally validate a linear metabolic pathway beginning with glutamine uptake and ending with bilirubin excretion from Fh1-deficient cells. This pathway, which involves the biosynthesis and degradation of haem, enables Fh1-deficient cells to use the accumulated TCA cycle metabolites and permits partial mitochondrial NADH production. We predicted and confirmed that targeting this pathway would render Fh1-deficient cells non-viable, while sparing wild-type Fh1-containing cells. This work goes beyond identifying a metabolic pathway that is induced in Fh1-deficient cells to demonstrate that inhibition of haem oxygenation is synthetically lethal when combined with Fh1 deficiency, providing a new potential target for treating HLRCC patients.

VL - 477 CP - 7363 M3 - 10.1038/nature10363 ER - TY - JOUR T1 - Horizontal transfer, not duplication, drives the expansion of protein families in prokaryotes JF - PLoS Genet Y1 - 2011 A1 - Todd Treangen A1 - Eduardo Rocha VL - 7 ER - TY - JOUR T1 - Identification of Schistosoma mansoni microRNAs. JF - BMC Genomics Y1 - 2011 A1 - Simões, Mariana C A1 - Lee, Jonathan A1 - Djikeng, Appolinaire A1 - Cerqueira, Gustavo C A1 - Zerlotini, Adhemar A1 - da Silva-Pereira, Rosiane A A1 - Dalby, Andrew R A1 - LoVerde, Philip A1 - El-Sayed, Najib M A1 - Oliveira, Guilherme KW - Animals KW - Computational Biology KW - Genome, Helminth KW - MicroRNAs KW - Schistosoma mansoni AB -

BACKGROUND: MicroRNAs (miRNAs) constitute a class of single-stranded RNAs which play a crucial role in regulating development and controlling gene expression by targeting mRNAs and triggering either translation repression or messenger RNA (mRNA) degradation. miRNAs are widespread in eukaryotes and to date over 14,000 miRNAs have been identified by computational and experimental approaches. Several miRNAs are highly conserved across species. In Schistosoma, the full set of miRNAs and their expression patterns during development remain poorly understood. Here we report on the development and implementation of a homology-based detection strategy to search for miRNA genes in Schistosoma mansoni. In addition, we report results on the experimental detection of miRNAs by means of cDNA cloning and sequencing of size-fractionated RNA samples.

RESULTS: Homology search using the high-throughput pipeline was performed with all known miRNAs in miRBase. A total of 6,211 mature miRNAs were used as reference sequences and 110 unique S. mansoni sequences were returned by BLASTn analysis. The existing mature miRNAs that produced these hits are reported, as well as the locations of the homologous sequences in the S. mansoni genome. All BLAST hits aligned with at least 95% of the miRNA sequence, resulting in alignment lengths of 19-24 nt. Following several filtering steps, 15 potential miRNA candidates were identified using this approach. By sequencing small RNA cDNA libraries from adult worm pairs, we identified 211 novel miRNA candidates in the S. mansoni genome. Northern blot analysis was used to detect the expression of the 30 most frequent sequenced miRNAs and to compare the expression level of these miRNAs between the lung stage schistosomula and adult worm stages. Expression of 11 novel miRNAs was confirmed by northern blot analysis and some presented a stage-regulated expression pattern. Three miRNAs previously identified from S. japonicum were also present in S. mansoni.

CONCLUSION: Evidence for the presence of miRNAs in S. mansoni is presented. The number of miRNAs detected by homology-based computational methods in S. mansoni is limited due to the lack of close relatives in the miRNA repository. In spite of this, the computational approach described here can likely be applied to the identification of pre-miRNA hairpins in other organisms. Construction and analysis of a small RNA library led to the experimental identification of 14 novel miRNAs from S. mansoni through a combination of molecular cloning, DNA sequencing and expression studies. Our results significantly expand the set of known miRNAs in multicellular parasites and provide a basis for understanding the structural and functional evolution of miRNAs in these metazoan parasites.

VL - 12 M3 - 10.1186/1471-2164-12-47 ER - TY - JOUR T1 - The Importance of Chitin in the Marine Environment JF - Marine BiotechnologyMarine Biotechnology Y1 - 2011 A1 - Souza, C. P. A1 - Almeida, B. C. A1 - Rita R. Colwell A1 - Rivera, I. N. G. AB - Chitin is the most abundant renewable polymer in the oceans and is an important source of carbon and nitrogen for marine organisms. The process of chitin degradation is a key step in the cycling of nutrients in the oceans and chitinolytic bacteria play a significant role in this process. These bacteria are autochthonous to both marine and freshwater ecosystems and produce chitinases that degrade chitin, an insoluble polysaccharide, to a biologically useful form. In this brief review, a description of the structure of chitin and diversity of chitinolytic bacteria in the oceans is provided, in the context of the significance of chitin degradation for marine life. ER - TY - JOUR T1 - Increased gene sampling provides stronger support for higher-level groups within gracillariid leaf mining moths and relatives (Lepidoptera: Gracillariidae) JF - BMC Evol BiolBMC Evol Biol Y1 - 2011 A1 - Kawahara, A. Y. A1 - Ohshima, I. A1 - Kawakita, A. A1 - Regier, J. C. A1 - Mitter, C. A1 - Michael P. Cummings A1 - Davis, D. R. A1 - Wagner, D. L. A1 - De Prinis, J. A1 - Lopez-Vaamonde, C. VL - 11:182 ER - TY - JOUR T1 - Increased gene sampling yields robust support for higher‐level clades within Bombycoidea (Lepidoptera) JF - Systematic EntomologySystematic Entomology Y1 - 2011 A1 - Zwick, Andreas A1 - Regier, Jerome C. A1 - Mitter, Charles A1 - Michael P. Cummings AB - This study has as its primary aim the robust resolution of higher-level relationships within the lepidopteran superfamily Bombycoidea. Our study builds on an earlier analysis of five genes (∼6.6 kbp) sequenced for 50 taxa from Bombycoidea and its sister group Lasiocampidae, plus representatives of other macrolepidoteran superfamilies. The earlier study failed to yield strong support for the monophyly of and basal splits within Bombycoidea, among others. Therefore, in an effort to increase support specifically for higher-level nodes, we generated 11.7 kbp of additional data from 20 genes for 24 of 50 bombycoid and lasiocampid taxa. The data from the genes are all derived from protein-coding nuclear genes previously used to resolve other lepidopteran relationships. With these additional data, all but a few higher-level nodes are strongly supported. Given our decision to minimize project costs by augmenting genes for only 24 of the 50 taxa, we explored whether the resulting pattern of missing data in the combined-gene matrix introduced a nonphylogenetic bias, a possibility reported by others. This was achieved by comparing node support values (i.e. nonparametric bootstrap values) based on likelihood and parsimony analyses of three datasets that differ in their number of taxa and level of missing data: 50 taxa/5 genes (dataset A), 50 taxa/25 genes (dataset B) and 24 taxa/25 genes (dataset C). Whereas datasets B and C provided similar results for common nodes, both frequently yielded higher node support relative to dataset A, arguing that: (i) more data yield increased node support and (ii) partial gene augmentation does not introduce an obvious nonphylogenetic bias. A comparison of single-gene bootstrap analyses identified four nodes for which one or two of the 25 genes provided modest to strong support for a grouping not recovered by the combined-gene result. As a summary proposal, two of these four groupings (one each within Bombycoidea and Lasiocampidae) were deemed sufficiently problematic to regard them as unresolved trichotomies. Since the alternative groupings were always highly localized on the tree, we did not judge a combined-gene analysis to present a problem outside those regions. Based on our robustly resolved results, we have revised the classification of Bombycoidea: the family Bombycidae is restricted to its nominate subfamily, and its tribe Epiini is elevated to subfamily rank (Epiinae stat.rev.), whereas the bombycid subfamily Phiditiinae is reinstated as a separate family (Phiditiidae stat.rev.). The bombycid subfamilies Oberthueriinae Kuznetzov & Stekolnikov, 1985, syn.nov. and Prismostictinae Forbes, 1955, syn.nov., and the family Mirinidae Kozlov, 1985, syn.nov. are established as subjective junior synonyms of Endromidae Boisduval, 1828. The family Anthelidae (Lasiocampoidea) is reincluded in the superfamily Bombycoidea. VL - 36 SN - 1365-3113 ER - TY - JOUR T1 - Increased methylation variation in epigenetic domains across cancer types JF - Nature Genetics Y1 - 2011 A1 - Hansen, Kasper Daniel A1 - Timp, Winston A1 - Bravo, Héctor Corrada A1 - Sabunciyan, Sarven A1 - Langmead, Benjamin A1 - McDonald, Oliver G A1 - Wen, Bo A1 - Wu, Hao A1 - Liu, Yun A1 - Diep, Dinh A1 - Briem, Eirikur A1 - Zhang, Kun A1 - Irizarry, Rafael A A1 - Feinberg, Andrew P VL - 43 UR - http://www.nature.com/doifinder/10.1038/ng.865 CP - 8 J1 - Nat Genet M3 - 10.1038/ng.865 ER - TY - JOUR T1 - Influence of host gene transcription level and orientation on HIV-1 latency in a primary-cell model JF - Journal of virologyJournal of virology Y1 - 2011 A1 - Shan, Liang A1 - Yang, Hung-Chih A1 - Rabi, S. Alireza A1 - Héctor Corrada Bravo A1 - Shroff, Neeta S. A1 - Irizarry, Rafael A. A1 - Zhang, Hao A1 - Margolick, Joseph B. A1 - Siliciano, Janet D. A1 - Siliciano, Robert F. KW - CD4-Positive T-Lymphocytes KW - Cells, Cultured KW - Gene Expression Profiling KW - Gene Expression Regulation, Viral KW - HIV-1 KW - HUMANS KW - Transcription, Genetic KW - Virus Integration KW - Virus Latency AB - Human immunodeficiency virus type 1 (HIV-1) establishes a latent reservoir in resting memory CD4(+) T cells. This latent reservoir is a major barrier to the eradication of HIV-1 in infected individuals and is not affected by highly active antiretroviral therapy (HAART). Reactivation of latent HIV-1 is a possible strategy for elimination of this reservoir. The mechanisms with which latency is maintained are unclear. In the analysis of the regulation of HIV-1 gene expression, it is important to consider the nature of HIV-1 integration sites. In this study, we analyzed the integration and transcription of latent HIV-1 in a primary CD4(+) T cell model of latency. The majority of integration sites in latently infected cells were in introns of transcription units. Serial analysis of gene expression (SAGE) demonstrated that more than 90% of those host genes harboring a latent integrated provirus were transcriptionally active, mostly at high levels. For latently infected cells, we observed a modest preference for integration in the same transcriptional orientation as the host gene (63.8% versus 36.2%). In contrast, this orientation preference was not observed in acutely infected or persistently infected cells. These results suggest that transcriptional interference may be one of the important factors in the establishment and maintenance of HIV-1 latency. Our findings suggest that disrupting the negative control of HIV-1 transcription by upstream host promoters could facilitate the reactivation of latent HIV-1 in some resting CD4(+) T cells. VL - 85 N1 - http://www.ncbi.nlm.nih.gov/pubmed/21430059?dopt=Abstract ER - TY - JOUR T1 - Influence of Host Gene Transcription Level and Orientation on HIV-1 Latency in a Primary-Cell Model JF - Journal of Virology Y1 - 2011 A1 - Shan, L. A1 - Yang, H.-C. A1 - Rabi, S. A. A1 - Bravo, H. C. A1 - Shroff, N. S. A1 - Irizarry, R. A. A1 - Zhang, H. A1 - Margolick, J. B. A1 - Siliciano, J. D. A1 - Siliciano, R. F. VL - 85 UR - http://jvi.asm.org/cgi/doi/10.1128/JVI.02536-10https://syndication.highwire.org/content/doi/10.1128/JVI.02536-10 CP - 11 J1 - Journal of Virology M3 - 10.1128/JVI.02536-10 ER - TY - JOUR T1 - Interaction of Vibrio cholerae non-O1/non-O139 with Copepods, Cladocerans and Competing Bacteria in the Large Alkaline Lake Neusiedler See, Austria JF - Microbial ecologyMicrobial ecology Y1 - 2011 A1 - Kirschner, A. K. T. A1 - Schauer, S. A1 - Steinberger, B. A1 - Wilhartitz, I. A1 - Grim, C. J. A1 - Huq, A. A1 - Rita R. Colwell A1 - Herzig, A. A1 - Sommer, R. AB - Vibrio cholerae is a human pathogen and natural inhabitant of aquatic environments. Serogroups O1/O139 have been associated with epidemic cholera, while non-O1/non-O139 serogroups usually cause human disease other than classical cholera. V. cholerae non-O1/non-O139 from the Neusiedler See, a large Central European lake, have caused ear and wound infections, including one case of fatal septicaemia. Recent investigations demonstrated rapid planktonic growth of V. cholerae non-O1/non-O139 and correlation with zooplankton biomass. The aim of this study was to elucidate the interaction of autochthonous V. cholerae with two dominant crustacean zooplankton species in the lake and investigate the influence of the natural bacterial community on this interaction. An existing data set was evaluated for statistical relationships between zooplankton species and V. cholerae and co-culture experiments were performed in the laboratory. A new fluorescence in situ hybridisation protocol was applied for quantification of V. cholerae non-O1/non-O139 cells, which significantly reduced analysis time. The experiments clearly demonstrated a significant relationship of autochthonous V. cholerae non-O1/non-O139 with cladocerans by promoting growth of V. cholerae non-O1/non-O139 in the water and on the surfaces of the cladocerans. In contrast, copepods had a negative effect on the growth of V. cholerae non-O1/non-O139 via competing bacteria from their surfaces. Thus, beside other known factors, biofilm formation by V. cholerae on crustacean zooplankton appears to be zooplankton taxon specific and may be controlled by the natural bacterial community. VL - 61 ER - TY - JOUR T1 - Long-term effects of ocean warming on the prokaryotic community: evidence from the vibrios JF - The ISME JournalThe ISME journal Y1 - 2011 A1 - Vezzulli, Luigi A1 - Brettar, Ingrid A1 - Pezzati, Elisabetta A1 - Reid, Philip C. A1 - Rita R. Colwell A1 - Höfle, Manfred G. A1 - Pruzzo, Carla KW - ecophysiology KW - ecosystems KW - environmental biotechnology KW - geomicrobiology KW - ISME J KW - microbe interactions KW - microbial communities KW - microbial ecology KW - microbial engineering KW - microbial epidemiology KW - microbial genomics KW - microorganisms AB - The long-term effects of ocean warming on prokaryotic communities are unknown because of lack of historical data. We overcame this gap by applying a retrospective molecular analysis to the bacterial community on formalin-fixed samples from the historical Continuous Plankton Recorder archive, which is one of the longest and most geographically extensive collections of marine biological samples in the world. We showed that during the last half century, ubiquitous marine bacteria of the Vibrio genus, including Vibrio cholerae, increased in dominance within the plankton-associated bacterial community of the North Sea, where an unprecedented increase in bathing infections related to these bacteria was recently reported. Among environmental variables, increased sea surface temperature explained 45% of the variance in Vibrio data, supporting the view that ocean warming is favouring the spread of vibrios and may be the cause of the globally increasing trend in their associated diseases. VL - 6 SN - 1751-7362 ER - TY - Generic T1 - MDMap: A system for data-driven layout and exploration of molecular dynamics simulations T2 - Biological Data Visualization (BioVis), 2011 IEEE Symposium on Y1 - 2011 A1 - Patro, R. A1 - Ip, Cheuk Yiu A1 - Bista, S. A1 - Cho, S. S. A1 - Thirumalai, D. A1 - Varshney, Amitabh KW - Biology KW - biomolecular KW - computing KW - data KW - digital KW - driven KW - DYNAMICS KW - exploration KW - folding KW - graph KW - landscapes KW - Layout KW - MDMap KW - method KW - molecular KW - processes KW - simulation KW - Simulations KW - space KW - state KW - Stochastic KW - THEORY KW - time-varying KW - Trajectory KW - transition AB - Contemporary molecular dynamics simulations result in a glut of simulation data, making analysis and discovery a difficult and burdensome task. We present MDMap, a system designed to summarize long-running molecular dynamics (MD) simulations. We represent a molecular dynamics simulation as a state transition graph over a set of intermediate (stable and semi-stable) states. The transitions amongst the states together with their frequencies represent the flow of a biomolecule through the trajectory space. MDMap automatically determines potential intermediate conformations and the transitions amongst them by analyzing the conformational space explored by the MD simulation. MDMap is an automated system to visualize MD simulations as state-transition diagrams, and can replace the current tedious manual layouts of biomolecular folding landscapes with an automated tool. The layout of the representative states and the corresponding transitions among them is presented to the user as a visual synopsis of the long-running MD simulation. We compare and contrast multiple presentations of the state transition diagrams, such as conformational embedding, and spectral, hierarchical, and force-directed graph layouts. We believe this system could provide a road-map for the visualization of other stochastic time-varying simulations in a variety of different domains. JA - Biological Data Visualization (BioVis), 2011 IEEE Symposium on ER - TY - JOUR T1 - Metagenomic 16S rDNA Targeted PCR-DGGE in Determining Bacterial Diversity in Aquatic Ecosystem JF - Bangladesh Journal of MicrobiologyBangladesh Journal of Microbiology Y1 - 2011 A1 - Hasan, Nur A. A1 - Chowdhury, W. Bari A1 - Rahim, Niaz A1 - Sultana, Marzia A1 - Shabnam, S. Antara A1 - Mai, Volker A1 - Ali, Afsar A1 - Morris, Glen J. A1 - Sack, R. Bradley A1 - Huq, Anwar A1 - Rita R. Colwell A1 - Endtz, Hubert Ph A1 - Cravioto, Alejandro A1 - Alam, Munirul AB - Bacterial numbers in surface water samples, collected randomly from six different water bodies, were estimated by acridine orange direct counting (AODC) and conventional culture-based heterotrophic plate counting (HPC). Bacterial genomic DNA was prepared from water samples by employing methods used for stool samples, including the population dynamics, were determined by primer extension of the 16S rDNA (V6/V8 region) using polymerase chain reaction (PCR), followed by denaturing gradient gel electrophoresis (DGGE), a metagenomic tool that is capable of separating unrelated DNAs based on the differences in their sequences and GC contents. The bacterial numbers in water samples ranged from 103 – 106 CFU/ mL for HPC and 104 – 107 cells/ mL for AODC, showing that a great majority of bacteria prevail as uncultivable which do not respond to culture methods that are used widely for tracking bacterial pathogens. The acridine orange-stained bacteria varied in sizes and shapes, and appeared either as planktonic (solitary) cells or as clusters of biofilms, showing the presence of diverse community under the epifluorescence microscope. The DGGE of the ca. 457 bp amplicons, as confirmed by agarose gel electrophoresis, produced bands that ranged in intensities and numbers from 18 to 31, with each band possibly indicating the presence of one or more closely related bacterial species. The enrichment of pathogenic bacteria in the aquatic ecosystem is known to precede the seasonal diarrhoeal outbreaks; therefore, bacterial community dynamics determined by Metagenomic 16S PCR-DGGE during pre-epidemic enrichment appears promising in predicting the upcoming diarrheal outbreaks. VL - 27 SN - 1011-9981 ER - TY - JOUR T1 - MetaPath: identifying differentially abundant metabolic pathways in metagenomic datasets JF - BMC ProceedingsBMC Proceedings Y1 - 2011 A1 - Liu, Bo A1 - M. Pop AB - Enabled by rapid advances in sequencing technology, metagenomic studies aim to characterize entire communities of microbes bypassing the need for culturing individual bacterial members. One major goal of metagenomic studies is to identify specific functional adaptations of microbial communities to their habitats. The functional profile and the abundances for a sample can be estimated by mapping metagenomic sequences to the global metabolic network consisting of thousands of molecular reactions. Here we describe a powerful analytical method (MetaPath) that can identify differentially abundant pathways in metagenomic datasets, relying on a combination of metagenomic sequence data and prior metabolic pathway knowledge. VL - 5 SN - 1753-6561 ER - TY - JOUR T1 - A Model for Early Prediction of Facial Nerve Recovery After Vestibular Schwannoma Surgery JF - Otology & Neurotology Y1 - 2011 A1 - Rivas, Alejandro A1 - Boahene, Kofi D. A1 - Bravo, Héctor Corrada A1 - Tan, Marietta A1 - Tamargo, Rafael J. A1 - Francis, Howard W. VL - 32 UR - http://content.wkhealth.com/linkback/openurl?sid=WKPTLP:landingpage&an=00129492-201107000-00019 CP - 5 J1 - Otology & Neurotology M3 - 10.1097/MAO.0b013e31821b0afd ER - TY - JOUR T1 - Next Generation Sequence Assembly with AMOS JF - Current Protocols in BioinformaticsCurrent Protocols in Bioinformatics Y1 - 2011 A1 - Todd Treangen A1 - Sommer, D. D. A1 - Angly, F. E. A1 - Koren, S. A1 - M. Pop PB - Wiley Online Library VL - 11 ER - TY - JOUR T1 - Population Dynamics of Vibrio Cholerae and Cholera in the Bangladesh Sundarbans: Role of Zooplankton Diversity JF - Applied and Environmental MicrobiologyAppl. Environ. Microbiol.Applied and Environmental MicrobiologyAppl. Environ. Microbiol. Y1 - 2011 A1 - De Magny, Guillaume Constantin A1 - Mozumder, Pronob K. A1 - Grim, Christopher J. A1 - Hasan, Nur A. A1 - Naser, M. Niamul A1 - Alam, Munirul A1 - Sack, Bradley A1 - Huq, Anwar A1 - Rita R. Colwell AB - Vibrio cholerae, a bacterium autochthonous to the aquatic environment, is the causative agent of cholera, a severe watery, life-threatening diarrhoeal disease occurring predominantly in developing countries. V. cholerae, including both serogroup O1 and O139, i.e. found in association with crustacean zooplankton, mainly copepods, and notably in ponds, rivers, and estuarine systems globally. The incidence of cholera and occurrence of V. cholerae pathogenic strains with zooplankton were studied in two areas of Bangladesh: Bakerganj and Mathbaria. Chitinous zooplankton communities of several bodies of water were analyzed in order to understand the interaction of zooplankton population composition with the population dynamics of pathogenic V. cholerae and incidence of cholera. Two dominant zooplankton groups were found to be consistently associated with detection of V. cholerae and/or occurrence of cholera cases, namely rotifers, and cladocerans, in addition to copepods. Local differences indicate there are subtle ecological factors that can influence interactions between V. cholerae, its plankton hosts, and the incidence of cholera. SN - 0099-2240, 1098-5336 ER - TY - JOUR T1 - Predicting selective drug targets in cancer through metabolic networks. JF - Mol Syst Biol Y1 - 2011 A1 - Folger, Ori A1 - Jerby, Livnat A1 - Frezza, Christian A1 - Gottlieb, Eyal A1 - Ruppin, Eytan A1 - Shlomi, Tomer KW - Cell Line, Tumor KW - Cell Proliferation KW - Computational Biology KW - Cytostatic Agents KW - Down-Regulation KW - Drug Delivery Systems KW - Gene Expression Regulation, Neoplastic KW - HUMANS KW - Metabolic Networks and Pathways KW - Models, Biological KW - Neoplasms KW - RNA, Small Interfering AB -

The interest in studying metabolic alterations in cancer and their potential role as novel targets for therapy has been rejuvenated in recent years. Here, we report the development of the first genome-scale network model of cancer metabolism, validated by correctly identifying genes essential for cellular proliferation in cancer cell lines. The model predicts 52 cytostatic drug targets, of which 40% are targeted by known, approved or experimental anticancer drugs, and the rest are new. It further predicts combinations of synthetic lethal drug targets, whose synergy is validated using available drug efficacy and gene expression measurements across the NCI-60 cancer cell line collection. Finally, potential selective treatments for specific cancers that depend on cancer type-specific downregulation of gene expression and somatic mutations are compiled.

VL - 7 M3 - 10.1038/msb.2011.35 ER - TY - JOUR T1 - ProPhylo: partial phylogenetic profiling to guide protein family construction and assignment of biological process JF - BMC bioinformaticsBMC Bioinformatics Y1 - 2011 A1 - Basu, Malay K. A1 - J. Selengut A1 - Haft, Daniel H. KW - algorithms KW - Archaea KW - Archaeal Proteins KW - DNA KW - Methane KW - Phylogeny KW - software AB - BACKGROUND: Phylogenetic profiling is a technique of scoring co-occurrence between a protein family and some other trait, usually another protein family, across a set of taxonomic groups. In spite of several refinements in recent years, the technique still invites significant improvement. To be its most effective, a phylogenetic profiling algorithm must be able to examine co-occurrences among protein families whose boundaries are uncertain within large homologous protein superfamilies. RESULTS: Partial Phylogenetic Profiling (PPP) is an iterative algorithm that scores a given taxonomic profile against the taxonomic distribution of families for all proteins in a genome. The method works through optimizing the boundary of each protein family, rather than by relying on prebuilt protein families or fixed sequence similarity thresholds. Double Partial Phylogenetic Profiling (DPPP) is a related procedure that begins with a single sequence and searches for optimal granularities for its surrounding protein family in order to generate the best query profiles for PPP. We present ProPhylo, a high-performance software package for phylogenetic profiling studies through creating individually optimized protein family boundaries. ProPhylo provides precomputed databases for immediate use and tools for manipulating the taxonomic profiles used as queries. CONCLUSION: ProPhylo results show universal markers of methanogenesis, a new DNA phosphorothioation-dependent restriction enzyme, and efficacy in guiding protein family construction. The software and the associated databases are freely available under the open source Perl Artistic License from ftp://ftp.jcvi.org/pub/data/ppp/. VL - 12 N1 - http://www.ncbi.nlm.nih.gov/pubmed/22070167?dopt=Abstract ER - TY - JOUR T1 - ProPhylo: partial phylogenetic profiling to guide protein family construction and assignment of biological process. JF - BMC Bioinformatics Y1 - 2011 A1 - Basu, Malay K A1 - Selengut, Jeremy D A1 - Haft, Daniel H KW - algorithms KW - Archaea KW - Archaeal Proteins KW - DNA KW - Methane KW - Phylogeny KW - software AB -

BACKGROUND: Phylogenetic profiling is a technique of scoring co-occurrence between a protein family and some other trait, usually another protein family, across a set of taxonomic groups. In spite of several refinements in recent years, the technique still invites significant improvement. To be its most effective, a phylogenetic profiling algorithm must be able to examine co-occurrences among protein families whose boundaries are uncertain within large homologous protein superfamilies.

RESULTS: Partial Phylogenetic Profiling (PPP) is an iterative algorithm that scores a given taxonomic profile against the taxonomic distribution of families for all proteins in a genome. The method works through optimizing the boundary of each protein family, rather than by relying on prebuilt protein families or fixed sequence similarity thresholds. Double Partial Phylogenetic Profiling (DPPP) is a related procedure that begins with a single sequence and searches for optimal granularities for its surrounding protein family in order to generate the best query profiles for PPP. We present ProPhylo, a high-performance software package for phylogenetic profiling studies through creating individually optimized protein family boundaries. ProPhylo provides precomputed databases for immediate use and tools for manipulating the taxonomic profiles used as queries.

CONCLUSION: ProPhylo results show universal markers of methanogenesis, a new DNA phosphorothioation-dependent restriction enzyme, and efficacy in guiding protein family construction. The software and the associated databases are freely available under the open source Perl Artistic License from ftp://ftp.jcvi.org/pub/data/ppp/.

VL - 12 M3 - 10.1186/1471-2105-12-434 ER - TY - JOUR T1 - Regulation of Lung Endoderm Progenitor Cell Behavior by miR302/367 JF - DevelopmentDevelopmentDevelopmentDevelopment Y1 - 2011 A1 - Tian, Ying A1 - Zhang, Yuzhen A1 - Hurd, Laura A1 - Sridhar Hannenhalli A1 - Liu, Feiyan A1 - Lu, Min Min A1 - Morrisey, Edward E. KW - Lung KW - MicroRNA KW - mouse KW - Progenitor AB - The temporal and spatial control of organ-specific endoderm progenitor development is poorly understood. miRNAs affect cell function by regulating programmatic changes in protein expression levels. We show that the miR302/367 cluster is a target of the transcription factor Gata6 in mouse lung endoderm and regulates multiple aspects of early lung endoderm progenitor development. miR302/367 is expressed at early stages of lung development, but its levels decline rapidly as development proceeds. Gain- and loss-of-function studies show that altering miR302/367 expression disrupts the balance of lung endoderm progenitor proliferation and differentiation, as well as apical-basal polarity. Increased miR302/367 expression results in the formation of an undifferentiated multi-layered lung endoderm, whereas loss of miR302/367 activity results in decreased proliferation and enhanced lung endoderm differentiation. miR302/367 coordinates the balance between proliferation and differentiation, in part, through direct regulation of Rbl2 and Cdkn1a, whereas apical-basal polarity is controlled by regulation of Tiam1 and Lis1. Thus, miR302/367 directs lung endoderm development by coordinating multiple aspects of progenitor cell behavior, including proliferation, differentiation and apical-basal polarity. VL - 138 SN - 0950-1991, 1477-9129 ER - TY - JOUR T1 - Repetitive DNA and next-generation sequencing: computational challenges and solutions JF - Nature Reviews Genetics Y1 - 2011 A1 - Todd Treangen A1 - Salzberg, Steven L ER - TY - JOUR T1 - A robust and rotationally invariant local surface descriptor with applications to non-local mesh processing JF - Graphical ModelsGraphical Models Y1 - 2011 A1 - Maximo, A. A1 - Patro, R. A1 - Varshney, Amitabh A1 - Farias, R. KW - Local descriptors KW - Non-local mesh processing KW - shape analysis KW - Similarity processing AB - In recent years, we have witnessed a striking increase in research concerning how to describe a meshed surface. These descriptors are commonly used to encode mesh properties or guide mesh processing, not to augment existing computations by replication. In this work, we first define a robust surface descriptor based on a local height field representation, and present a transformation via the extraction of Zernike moments. Unlike previous work, our local surface descriptor is innately rotationally invariant. Second, equipped with this novel descriptor, we present SAMPLE – similarity augmented mesh processing using local exemplars – a method which uses feature neighbourhoods to propagate mesh processing done in one part of the mesh, the local exemplar, to many others. Finally, we show that SAMPLE can be used in a number of applications, such as detail transfer and parameterization. VL - 73 SN - 1524-0703 ER - TY - JOUR T1 - Role of Zooplankton Diversity in Vibrio Cholerae Population Dynamics and in the Incidence of Cholera in the Bangladesh Sundarbans JF - Applied and Environmental MicrobiologyAppl. Environ. Microbiol.Applied and Environmental MicrobiologyAppl. Environ. Microbiol. Y1 - 2011 A1 - De Magny, Guillaume Constantin A1 - Mozumder, Pronob K. A1 - Grim, Christopher J. A1 - Hasan, Nur A. A1 - Naser, M. Niamul A1 - Alam, Munirul A1 - Sack, R. Bradley A1 - Huq, Anwar A1 - Rita R. Colwell AB - Vibrio cholerae, a bacterium autochthonous to the aquatic environment, is the causative agent of cholera, a severe watery, life-threatening diarrheal disease occurring predominantly in developing countries. V. cholerae, including both serogroups O1 and O139, is found in association with crustacean zooplankton, mainly copepods, and notably in ponds, rivers, and estuarine systems globally. The incidence of cholera and occurrence of pathogenic V. cholerae strains with zooplankton were studied in two areas of Bangladesh: Bakerganj and Mathbaria. Chitinous zooplankton communities of several bodies of water were analyzed in order to understand the interaction of the zooplankton population composition with the population dynamics of pathogenic V. cholerae and incidence of cholera. Two dominant zooplankton groups were found to be consistently associated with detection of V. cholerae and/or occurrence of cholera cases, namely, rotifers and cladocerans, in addition to copepods. Local differences indicate there are subtle ecological factors that can influence interactions between V. cholerae, its plankton hosts, and the incidence of cholera. VL - 77 SN - 0099-2240, 1098-5336 ER - TY - JOUR T1 - Social Snapshot: A System for Temporally Coupled Social Photography JF - Computer Graphics and Applications, IEEEComputer Graphics and Applications, IEEE Y1 - 2011 A1 - Patro, R. A1 - Ip, Cheuk Yiu A1 - Bista, S. A1 - Varshney, Amitabh KW - 3D KW - ACQUISITION KW - computing KW - coupled KW - data KW - Photography KW - reconstruction KW - sciences KW - snapshot KW - social KW - spatiotemporal KW - temporally AB - Social Snapshot actively acquires and reconstructs temporally dynamic data. The system enables spatiotemporal 3D photography using commodity devices, assisted by their auxiliary sensors and network functionality. It engages users, making them active rather than passive participants in data acquisition. VL - 31 SN - 0272-1716 ER - TY - JOUR T1 - Suppression subtractive hybridization PCR isolation of cDNAs from a Caribbean soft coral JF - Electronic Journal of BiotechnologyElectronic Journal of Biotechnology Y1 - 2011 A1 - Lopez, J. V. A1 - Ledger, A. A1 - Santiago-Vázquez, L. Z. A1 - M. Pop A1 - Sommer, D. D. A1 - Ranzer, L. K. A1 - Feldman, R. A. A1 - Russell, G. K. PB - SciELO Chile VL - 14 ER - TY - JOUR T1 - Temperature regulation of virulence factors in the pathogen Vibrio coralliilyticus JF - The ISME JournalThe ISME journal Y1 - 2011 A1 - Kimes, Nikole E. A1 - Grim, Christopher J. A1 - Johnson, Wesley R. A1 - Hasan, Nur A. A1 - Tall, Ben D. A1 - Kothary, Mahendra H. A1 - Kiss, Hajnalka A1 - Munk, A. Christine A1 - Tapia, Roxanne A1 - Green, Lance A1 - Detter, Chris A1 - Bruce, David C. A1 - Brettin, Thomas S. A1 - Rita R. Colwell A1 - Morris, Pamela J. KW - ecophysiology KW - ecosystems KW - environmental biotechnology KW - geomicrobiology KW - ISME J KW - microbe interactions KW - microbial communities KW - microbial ecology KW - microbial engineering KW - microbial epidemiology KW - microbial genomics KW - microorganisms AB - Sea surface temperatures (SST) are rising because of global climate change. As a result, pathogenic Vibrio species that infect humans and marine organisms during warmer summer months are of growing concern. Coral reefs, in particular, are already experiencing unprecedented degradation worldwide due in part to infectious disease outbreaks and bleaching episodes that are exacerbated by increasing SST. For example, Vibrio coralliilyticus, a globally distributed bacterium associated with multiple coral diseases, infects corals at temperatures above 27 °C. The mechanisms underlying this temperature-dependent pathogenicity, however, are unknown. In this study, we identify potential virulence mechanisms using whole genome sequencing of V. coralliilyticus ATCC (American Type Culture Collection) BAA-450. Furthermore, we demonstrate direct temperature regulation of numerous virulence factors using proteomic analysis and bioassays. Virulence factors involved in motility, host degradation, secretion, antimicrobial resistance and transcriptional regulation are upregulated at the higher virulent temperature of 27 °C, concurrent with phenotypic changes in motility, antibiotic resistance, hemolysis, cytotoxicity and bioluminescence. These results provide evidence that temperature regulates multiple virulence mechanisms in V. coralliilyticus, independent of abundance. The ecological and biological significance of this temperature-dependent virulence response is reinforced by climate change models that predict tropical SST to consistently exceed 27 °C during the spring, summer and fall seasons. We propose V. coralliilyticus as a model Gram-negative bacterium to study temperature-dependent pathogenicity in Vibrio-related diseases. VL - 6 SN - 1751-7362 ER - TY - JOUR T1 - Transcriptional Regulation Via TF-Modifying Enzymes: An Integrative Model-Based Analysis JF - Nucleic Acids ResearchNucl. Acids Res.Nucleic Acids ResearchNucl. Acids Res. Y1 - 2011 A1 - Everett, Logan J. A1 - Jensen, Shane T. A1 - Sridhar Hannenhalli AB - Transcription factor activity is largely regulated through post-translational modification. Here, we report the first integrative model of transcription that includes both interactions between transcription factors and promoters, and between transcription factors and modifying enzymes. Simulations indicate that our method is robust against noise. We validated our tool on a well-studied stress response network in yeast and on a STAT1-mediated regulatory network in human B cells. Our work represents a significant step toward a comprehensive model of gene transcription. VL - 39 SN - 0305-1048, 1362-4962 ER - TY - JOUR T1 - Vibrio Cholerae O1 Detection in Estuarine and Coastal Zooplankton JF - Journal of Plankton ResearchJ. Plankton Res.Journal of Plankton ResearchJ. Plankton Res. Y1 - 2011 A1 - Martinelli Filho, José E. A1 - Lopes, Rubens M. A1 - Rivera, Irma N. G. A1 - Rita R. Colwell KW - DFA KW - estuary KW - plankton KW - Southwest Atlantic AB - Vibrio cholerae is an autochthonous marine bacterium, and its association with diverse planktonic crustaceans has been extensively investigated; however, the presence of V. cholerae on individuals of most phyla of planktonic animals is still incompletely understood. The objective of this study was to analyze the distribution of V. cholerae serogroup O1 associated with specific zooplankton taxa in an estuary and the adjacent continental shelf of the southeastern Brazilian coast. The occurrence of the bacterium was assessed in zooplankton samples, specifically on the most abundant taxa, using direct fluorescence assay (DFA) and direct viable count–direct fluorescence assay (DVC–DFA) methods. Vibrio cholerae O1 was detected in 88% of samples collected from the Santos-Bertioga estuary and in 67% of samples from the shelf. The salinity of the estuarine water ranged from 21.8 to 34.6, significantly lower than the shelf water which was 32.1–36.1. Salinity was the only environmental variable measured that displayed a significant correlation with the presence of V. cholerae (P< 0.05). Vibrio cholerae O1 was detected in chaetognaths, pluteus larvae of echinoderms and planktonic fish eggs (Engraulidae), all new sites for this bacterium. VL - 33 SN - 0142-7873, 1464-3774 ER - TY - JOUR T1 - Warming Oceans, Phytoplankton, and River Discharge: Implications for Cholera Outbreaks JF - The American Journal of Tropical Medicine and HygieneAm J Trop Med HygThe American Journal of Tropical Medicine and HygieneAm J Trop Med Hyg Y1 - 2011 A1 - Jutla, Antarpreet S. A1 - Akanda, Ali S. A1 - Griffiths, Jeffrey K. A1 - Rita R. Colwell A1 - Islam, Shafiqul AB - Phytoplankton abundance is inversely related to sea surface temperature (SST). However, a positive relationship is observed between SST and phytoplankton abundance in coastal waters of Bay of Bengal. This has led to an assertion that in a warming climate, rise in SST may increase phytoplankton blooms and, therefore, cholera outbreaks. Here, we explain why a positive SST-phytoplankton relationship exists in the Bay of Bengal and the implications of such a relationship on cholera dynamics. We found clear evidence of two independent physical drivers for phytoplankton abundance. The first one is the widely accepted phytoplankton blooming produced by the upwelling of cold, nutrient-rich deep ocean waters. The second, which explains the Bay of Bengal findings, is coastal phytoplankton blooming during high river discharges with terrestrial nutrients. Causal mechanisms should be understood when associating SST with phytoplankton and subsequent cholera outbreaks in regions where freshwater discharge are a predominant mechanism for phytoplankton production. VL - 85 SN - 0002-9637 ER - TY - JOUR T1 - Alignment and clustering of phylogenetic markers - implications for microbial diversity studies JF - BMC BioinformaticsBMC Bioinformatics Y1 - 2010 A1 - White, James R. A1 - Navlakha, Saket A1 - Nagarajan, Niranjan A1 - Ghodsi, Mohammad-Reza A1 - Kingsford, Carl A1 - M. Pop AB - Molecular studies of microbial diversity have provided many insights into the bacterial communities inhabiting the human body and the environment. A common first step in such studies is a survey of conserved marker genes (primarily 16S rRNA) to characterize the taxonomic composition and diversity of these communities. To date, however, there exists significant variability in analysis methods employed in these studies. VL - 11 SN - 1471-2105 ER - TY - JOUR T1 - The Alveolate Perkinsus marinus: biological insights from EST gene discovery. JF - BMC Genomics Y1 - 2010 A1 - Joseph, Sandeep J A1 - Fernández-Robledo, José A A1 - Gardner, Malcolm J A1 - El-Sayed, Najib M A1 - Kuo, Chih-Horng A1 - Schott, Eric J A1 - Wang, Haiming A1 - Kissinger, Jessica C A1 - Vasta, Gerardo R KW - Alveolata KW - Animals KW - Expressed Sequence Tags KW - Ostreidae KW - Phylogeny AB -

BACKGROUND: Perkinsus marinus, a protozoan parasite of the eastern oyster Crassostrea virginica, has devastated natural and farmed oyster populations along the Atlantic and Gulf coasts of the United States. It is classified as a member of the Perkinsozoa, a recently established phylum considered close to the ancestor of ciliates, dinoflagellates, and apicomplexans, and a key taxon for understanding unique adaptations (e.g. parasitism) within the Alveolata. Despite intense parasite pressure, no disease-resistant oysters have been identified and no effective therapies have been developed to date.

RESULTS: To gain insight into the biological basis of the parasite's virulence and pathogenesis mechanisms, and to identify genes encoding potential targets for intervention, we generated>31,000 5' expressed sequence tags (ESTs) derived from four trophozoite libraries generated from two P. marinus strains. Trimming and clustering of the sequence tags yielded 7,863 unique sequences, some of which carry a spliced leader. Similarity searches revealed that 55% of these had hits in protein sequence databases, of which 1,729 had their best hit with proteins from the chromalveolates (E-value

CONCLUSIONS: Our transcriptome analysis of P. marinus, the first for any member of the Perkinsozoa, contributes new insight into its biology and taxonomic position. It provides a very informative, albeit preliminary, glimpse into the expression of genes encoding functionally relevant proteins as potential targets for chemotherapy, and evidence for the presence of a relict plastid. Further, although P. marinus sequences display significant similarity to those from both apicomplexans and dinoflagellates, the presence of trans-spliced transcripts confirms the previously established affinities with the latter. The EST analysis reported herein, together with the recently completed sequence of the P. marinus genome and the development of transfection methodology, should result in improved intervention strategies against dermo disease.

VL - 11 M3 - 10.1186/1471-2164-11-228 ER - TY - JOUR T1 - Assembly complexity of prokaryotic genomes using short reads JF - BMC bioinformaticsBMC Bioinformatics Y1 - 2010 A1 - Kingsford, Carl A1 - Schatz, M. A1 - M. Pop PB - BioMed Central Ltd VL - 11 ER - TY - JOUR T1 - Broader incorporation of bioinformatics in education: opportunities and challenges JF - Brief BioinformBrief Bioinform Y1 - 2010 A1 - Michael P. Cummings A1 - Temple, G. G. AB - The major opportunities for broader incorporation of bioinformatics in education can be placed into three general categories: general applicability of bioinformatics in life science and related curricula; inherent fit of bioinformatics for promoting student learning in most biology programs; and the general experience and associated comfort students have with computers and technology. Conversely, the major challenges for broader incorporation of bioinformatics in education can be placed into three general categories: required infrastructure and logistics; instructor knowledge of bioinformatics and continuing education; and the breadth of bioinformatics, and the diversity of students and educational objectives. Broader incorporation of bioinformatics at all education levels requires overcoming the challenges to using transformative computer- requiring learning activities, assisting faculty in collecting assessment data on mastery of student learning outcomes, as well as creating more faculty development opportunities that span diverse skill levels, with an emphasis placed on providing resource materials that are kept up-to-date as the field and tools change. VL - 11 ER - TY - JOUR T1 - Comparative genomic analysis reveals evidence of two novel Vibrio species closely related to V. cholerae JF - BMC MicrobiologyBMC Microbiology Y1 - 2010 A1 - Bradd, H. A1 - Christopher, G. A1 - Nur, H. A1 - Seon-Young, C. A1 - Jongsik, C. A1 - Thomas, B. A1 - David, B. A1 - Jean, C. A1 - Chris, D. J. A1 - Cliff, H. A1 - Rita R. Colwell AB - In recent years genome sequencing has been used to characterize new bacterial species, a method of analysis available as a result of improved methodology and reduced cost. Included in a constantly expanding list of Vibrio species are several that have been reclassified as novel members of the Vibrionaceae. The description of two putative new Vibrio species, Vibrio sp. RC341 and Vibrio sp. RC586 for which we propose the names V. metecus and V. parilis, respectively, previously characterized as non-toxigenic environmental variants of V. cholerae is presented in this study. Results Based on results of whole-genome average nucleotide identity (ANI), average amino acid identity (AAI), rpoB similarity, MLSA, and phylogenetic analysis, the new species are concluded to be phylogenetically closely related to V. cholerae and V. mimicus. Vibrio sp. RC341 and Vibrio sp. RC586 demonstrate features characteristic of V. cholerae and V. mimicus, respectively, on differential and selective media, but their genomes show a 12 to 15% divergence (88 to 85% ANI and 92 to 91% AAI) compared to the sequences of V. cholerae and V. mimicus genomes (ANI <95% and AAI <96% indicative of separate species). Vibrio sp. RC341 and Vibrio sp. RC586 share 2104 ORFs (59%) and 2058 ORFs (56%) with the published core genome of V. cholerae and 2956 (82%) and 3048 ORFs (84%) with V. mimicus MB-451, respectively. The novel species share 2926 ORFs with each other (81% Vibrio sp. RC341 and 81% Vibrio sp. RC586). Virulence-associated factors and genomic islands of V. cholerae and V. mimicus, including VSP-I and II, were found in these environmental Vibrio spp. Conclusions Results of this analysis demonstrate these two environmental vibrios, previously characterized as variant V. cholerae strains, are new species which have evolved from ancestral lineages of the V. cholerae and V. mimicus clade. The presence of conserved integration loci for genomic islands as well as evidence of horizontal gene transfer between these two new species, V. cholerae, and V. mimicus suggests genomic islands and virulence factors are transferred between these species. VL - 10 ER - TY - JOUR T1 - Comparative Genomics of Clinical and Environmental Vibrio Mimicus JF - Proceedings of the National Academy of SciencesPNASProceedings of the National Academy of SciencesPNAS Y1 - 2010 A1 - Hasan, Nur A. A1 - Grim, Christopher J. A1 - Haley, Bradd J. A1 - Jongsik, Chun A1 - Alam, Munirul A1 - Taviani, Elisa A1 - Mozammel, Hoq A1 - Munk, A. Christine A1 - Rita R. Colwell AB - Whether Vibrio mimicus is a variant of Vibrio cholerae or a separate species has been the subject of taxonomic controversy. A genomic analysis was undertaken to resolve the issue. The genomes of V. mimicus MB451, a clinical isolate, and VM223, an environmental isolate, comprise ca. 4,347,971 and 4,313,453 bp and encode 3,802 and 3,290 ORFs, respectively. As in other vibrios, chromosome I (C-I) predominantly contains genes necessary for growth and viability, whereas chromosome II (C-II) bears genes for adaptation to environmental change. C-I harbors many virulence genes, including some not previously reported in V. mimicus, such as mannose-sensitive hemagglutinin (MSHA), and enterotoxigenic hemolysin (HlyA); C-II encodes a variant of Vibrio pathogenicity island 2 (VPI-2), and Vibrio seventh pandemic island II (VSP-II) cluster of genes. Extensive genomic rearrangement in C-II indicates it is a hot spot for evolution and genesis of speciation for the genus Vibrio. The number of virulence regions discovered in this study (VSP-II, MSHA, HlyA, type IV pilin, PilE, and integron integrase, IntI4) with no notable difference in potential virulence genes between clinical and environmental strains suggests these genes also may play a role in the environment and that pathogenic strains may arise in the environment. Significant genome synteny with prototypic pre-seventh pandemic strains of V. cholerae was observed, and the results of phylogenetic analysis support the hypothesis that, in the course of evolution, V. mimicus and V. cholerae diverged from a common ancestor with a prototypic sixth pandemic genomic backbone. VL - 107 SN - 0027-8424, 1091-6490 ER - TY - JOUR T1 - Computational Approaches for Genome Assembly Validation JF - Biological Data MiningBiological Data Mining Y1 - 2010 A1 - Choi, J. H. A1 - Tang, H. A1 - Kim, S. A1 - M. Pop ER - TY - JOUR T1 - Conversion of viable but nonculturable Vibrio cholerae to the culturable state by co‐culture with eukaryotic cells JF - Microbiology and ImmunologyMicrobiology and Immunology Y1 - 2010 A1 - Senoh, Mitsutoshi A1 - Ghosh‐Banerjee, Jayeeta A1 - Ramamurthy, Thandavarayan A1 - Hamabata, Takashi A1 - Kurakawa, Takashi A1 - Takeda, Makoto A1 - Rita R. Colwell A1 - Nair, G. Balakrish A1 - Takeda, Yoshifumi KW - conversion to culturability KW - co‐culture KW - eukaryotic cell KW - viable but nonculturable (VBNC) Vibrio cholerae AB - VBNC Vibrio cholerae O139 VC-280 obtained by incubation in 1% solution of artificial sea water IO at 4°C for 74 days converted to the culturable state when co-cultured with CHO cells. Other eukaryotic cell lines, including HT-29, Caco-2, T84, HeLa, and Intestine 407, also supported conversion of VBNC cells to the culturable state. Conversion of VBNC V. cholerae O1 N16961 and V. cholerae O139 VC-280/pG13 to the culturable state, under the same conditions, was also confirmed. When VBNC V. cholerae O139 VC-280 was incubated in 1% IO at 4°C for up to 91 days, the number of cells converted by co-culture with CHO cells declined with each additional day of incubation and after 91 days conversion was not observed. VL - 54 SN - 1348-0421 ER - TY - JOUR T1 - Correlated Changes Between Regulatory Cis Elements and Condition-Specific Expression in Paralogous Gene Families JF - Nucleic Acids ResearchNucl. Acids Res.Nucleic Acids ResearchNucl. Acids Res. Y1 - 2010 A1 - Singh, Larry N. A1 - Sridhar Hannenhalli AB - Gene duplication is integral to evolution, providing novel opportunities for organisms to diversify in function. One fundamental pathway of functional diversification among initially redundant gene copies, or paralogs, is via alterations in their expression patterns. Although the mechanisms underlying expression divergence are not completely understood, transcription factor binding sites and nucleosome occupancy are known to play a significant role in the process. Previous attempts to detect genomic variations mediating expression divergence in orthologs have had limited success for two primary reasons. First, it is inherently challenging to compare expressions among orthologs due to variable trans-acting effects and second, previous studies have quantified expression divergence in terms of an overall similarity of expression profiles across multiple samples, thereby obscuring condition-specific expression changes. Moreover, the inherently inter-correlated expressions among homologs present statistical challenges, not adequately addressed in many previous studies. Using rigorous statistical tests, here we characterize the relationship between cis element divergence and condition-specific expression divergence among paralogous genes in Saccharomyces cerevisiae. In particular, among all combinations of gene family and TFs analyzed, we found a significant correlation between TF binding and the condition-specific expression patterns in over 20% of the cases. In addition, incorporating nucleosome occupancy reveals several additional correlations. For instance, our results suggest that GAL4 binding plays a major role in the expression divergence of the genes in the sugar transporter family. Our work presents a novel means of investigating the cis regulatory changes potentially mediating expression divergence in paralogous gene families under specific conditions. VL - 38 SN - 0305-1048, 1362-4962 ER - TY - JOUR T1 - Discovery of novel Vibrio cholerae VSP‐II genomic islands using comparative genomic analysis JF - FEMS Microbiology LettersFEMS Microbiology Letters Y1 - 2010 A1 - Taviani, Elisa A1 - Grim, Christopher J. A1 - Choi, Jinna A1 - Jongsik, Chun A1 - Haley, Bradd A1 - Hasan, Nur A. A1 - Huq, Anwar A1 - Rita R. Colwell KW - Vibrio cholerae KW - Vibrio mimicus KW - VPS‐II AB - This report describes Vibrio seventh pandemic island II (VSP-II) and three novel variants revealed by comparative genomics of 23 Vibrio cholerae strains and their presence among a large and diverse collection of V. cholerae isolates. Three VSP-II variants were reported previously and our results demonstrate the presence of three novel VSP-II in clinical and environmental V. cholerae marked by major deletions and genetic rearrangements. A new VSP-II cluster was found in the seventh pandemic V. cholerae O1 El Tor strain CIRS101, which is dominant (95%) among the recent (2004–2007) seven pandemic V. cholerae O1 El Tor isolates from two endemic sites, but was not found in older strains from the same region. Two other variants were found in V. cholerae TMA21 and RC385, two environmental strains from coastal Brazil and the Chesapeake Bay, respectively, the latter being prevalent among environmental V. cholerae non-O1/non-O139 and Vibrio mimicus. The results of this study indicate that the VSP-II island has undergone significant rearrangement through a complex evolutionary pathway in V. cholerae. Interestingly, one of the new VSP-II revealed the presence of ‘old’ and ‘new’V. cholerae O1 El Tor pandemic clones circulating in some of the areas where cholera is endemic. VL - 308 SN - 1574-6968 ER - TY - JOUR T1 - Diversity and distribution of cholix toxin, a novel ADP‐ribosylating factor from Vibrio cholerae JF - Environmental Microbiology ReportsEnvironmental Microbiology Reports Y1 - 2010 A1 - Purdy, Alexandra E. A1 - Balch, Deborah A1 - Lizárraga‐Partida, Marcial Leonardo A1 - Islam, Mohammad Sirajul A1 - Martinez‐Urtaza, Jaime A1 - Huq, Anwar A1 - Rita R. Colwell A1 - Bartlett, Douglas H. AB - Non-toxigenic non-O1, non-O139 Vibrio cholerae strains isolated from both environmental and clinical settings carry a suite of virulence factors aside from cholera toxin. Among V. cholerae strains isolated from coastal waters of southern California, this includes cholix toxin, an ADP-ribosylating factor that is capable of halting protein synthesis in eukaryotic cells. The prevalence of the gene encoding cholix toxin, chxA, was assessed among a collection of 155 diverse V. cholerae strains originating from both clinical and environmental settings in Bangladesh and Mexico and other countries around the globe. The chxA gene was present in 47% of 83 non-O1, non-O139 strains and 16% of 72 O1/O139 strains screened as part of this study. A total of 86 chxA gene sequences were obtained, and phylogenetic analysis revealed that they fall into two distinct clades. These two clades were also observed in the phylogenies of several housekeeping genes, suggesting that the divergence observed in chxA extends to other regions of the V. cholerae genome, and most likely has arisen from vertical descent rather than horizontal transfer. Our results clearly indicate that ChxA is a major toxin of V. cholerae with a worldwide distribution that is preferentially associated with non-pandemic strains. VL - 2 SN - 1758-2229 ER - TY - JOUR T1 - Effect on Human Cells of Environmental Vibrio Parahaemolyticus Strains Carrying Type III Secretion System 2 JF - Infection and ImmunityInfect. Immun.Infection and ImmunityInfect. Immun. Y1 - 2010 A1 - Caburlotto, Greta A1 - Lleò, Maria M. A1 - Hilton, Tamara A1 - Huq, Anwar A1 - Rita R. Colwell A1 - Kaper, James B. AB - Vibrio parahaemolyticus is an inhabitant of estuarine and marine environments that causes seafood-borne gastroenteritis worldwide. Recently, a type 3 secretion system (T3SS2) able to secrete and translocate virulence factors into the eukaryotic cell has been identified in a pathogenicity island (VP-PAI) located on the smaller chromosome. These virulence-related genes have previously been detected only in clinical strains. Classical virulence genes for this species (tdh, trh) are rarely detected in environmental strains, which are usually considered to lack virulence potential. However, during screening of a collection of environmental V. parahaemolyticus isolates obtained in the North Adriatic Sea in Italy, a number of marine strains carrying virulence-related genes, including genes involved in the T3SS2, were detected. In this study, we investigated the pathogenic potential of these marine V. parahaemolyticus strains by studying their adherence ability, their cytotoxicity, their effect on zonula occludin protein 1 (ZO-1) of the tight junctions, and their effect on transepithelial resistance (TER) in infected Caco-2 cells. By performing a reverse transcription-PCR, we also tested the expression of the T3SS2 genes vopT and vopB2, encoding an effector and a translocon protein, respectively. Our results indicate that, similarly to clinical strains, marine V. parahaemolyticus strains carrying vopT and vopB2 and that other genes included in the VP-PAI are capable of adhering to human cells and of causing cytoskeletal disruption and loss of membrane integrity in infected cells. On the basis of data presented here, environmental V. parahaemolyticus strains should be included in coastal water surveillance plans, as they may represent a risk for human health. VL - 78 SN - 0019-9567, 1098-5522 ER - TY - JOUR T1 - Environmental reservoirs of Vibrio cholerae and their role in cholera JF - Environmental Microbiology ReportsEnvironmental Microbiology Reports Y1 - 2010 A1 - Vezzulli, Luigi A1 - Pruzzo, Carla A1 - Huq, Anwar A1 - Rita R. Colwell AB - In the aquatic environment, Vibrio cholerae has been reported to be associated with a variety of living organisms, including animals with an exoskeleton of chitin, aquatic plants, protozoa, bivalves, waterbirds, as well as abiotic substrates (e.g. sediments). Most of these are well-known or putative environmental reservoirs for the bacterium, defined as places where the pathogen lives over time, with the potential to be released and to cause human infection. Environmental reservoirs also serve as V. cholerae disseminators and vectors. They can be responsible for the start of an epidemic, may be critical to cholera endemicity, and affect the evolution of pathogen virulence. To date, in addition to the generally recognized role of zooplankton as the largest environmental reservoir for V. cholerae, other environmental reservoirs play some role in cholera epidemiology by favouring persistence of the pathogen during inter-epidemic periods. Little is known about the ecological factors affecting V. cholerae survival in association with aquatic substrates. Studies aimed at these aspects, i.e. understanding how environmental reservoirs interact, are affected by climate, and contribute to disease epidemiology, will be useful for understanding global implications of V. cholerae and the disease cholera. VL - 2 SN - 1758-2229 ER - TY - JOUR T1 - Evolutionary dynamics of U12-type spliceosomal introns. JF - BMC Evol Biol Y1 - 2010 A1 - Lin, Chiao-Feng A1 - Mount, Stephen M A1 - Jarmołowski, Artur A1 - Makałowski, Wojciech KW - Animals KW - Arabidopsis KW - Evolution, Molecular KW - HUMANS KW - Introns KW - RNA, Small Nuclear KW - Spliceosomes AB -

BACKGROUND: Many multicellular eukaryotes have two types of spliceosomes for the removal of introns from messenger RNA precursors. The major (U2) spliceosome processes the vast majority of introns, referred to as U2-type introns, while the minor (U12) spliceosome removes a small fraction (less than 0.5%) of introns, referred to as U12-type introns. U12-type introns have distinct sequence elements and usually occur together in genes with U2-type introns. A phylogenetic distribution of U12-type introns shows that the minor splicing pathway appeared very early in eukaryotic evolution and has been lost repeatedly.

RESULTS: We have investigated the evolution of U12-type introns among eighteen metazoan genomes by analyzing orthologous U12-type intron clusters. Examination of gain, loss, and type switching shows that intron type is remarkably conserved among vertebrates. Among 180 intron clusters, only eight show intron loss in any vertebrate species and only five show conversion between the U12 and the U2-type. Although there are only nineteen U12-type introns in Drosophila melanogaster, we found one case of U2 to U12-type conversion, apparently mediated by the activation of cryptic U12 splice sites early in the dipteran lineage. Overall, loss of U12-type introns is more common than conversion to U2-type and the U12 to U2 conversion occurs more frequently among introns of the GT-AG subtype than among introns of the AT-AC subtype. We also found support for natural U12-type introns with non-canonical terminal dinucleotides (CT-AC, GG-AG, and GA-AG) that have not been previously reported.

CONCLUSIONS: Although complete loss of the U12-type spliceosome has occurred repeatedly, U12 introns are extremely stable in some taxa, including eutheria. Loss of U12 introns or the genes containing them is more common than conversion to the U2-type. The degeneracy of U12-type terminal dinucleotides among natural U12-type introns is higher than previously thought.

VL - 10 M3 - 10.1186/1471-2148-10-47 ER - TY - CHAP T1 - Evolutionary framework for Lepidoptera model systems T2 - Genetics and Molecular Biology of LepidopteraGenetics and Molecular Biology of Lepidoptera Y1 - 2010 A1 - Roe, A. A1 - Weller, S. A1 - Baixeras, J. A1 - Brown, J. W. A1 - Michael P. Cummings A1 - Davis, D. R. A1 - Horak, M. A1 - Kawahara, A. Y. A1 - Mitter, C. A1 - Parr, C. S. A1 - Regier, J. C. A1 - Rubinoff, D. A1 - Simonsen, T. J. A1 - Wahlberg, N. A1 - Zwick, A. ED - Goldsmith, M. ED - Marec, F. AB - “Model systems” are specific organisms upon which detailed studies have been conducted examining a fundamental biological question. If the studies are robust, their results can be extrapolated among an array of organisms that possess features in common with the subject organism. The true power of model systems lies in the ability to extrapolate these details across larger groups of organisms. In order to generalize these results, comparative studies are essential and require that model systems be placed into their evolutionary or phylogenetic context. This chapter examines model systems in the insect order Lepidoptera from the perspective of several different superfamilies. Historically, many species of Lepidoptera have been essential in the development of invaluable model systems in the fields of development biology, genetics, molecular biology, physiology, co-evolution, population dynamics, and ecology. JA - Genetics and Molecular Biology of LepidopteraGenetics and Molecular Biology of Lepidoptera PB - Taylor & Francis CY - Boca Raton ER - TY - Generic T1 - Exploring Biological Network Dynamics with Ensembles of Graph Partitions T2 - Proceedings of the PSB Pacific Symposium on Biocomputing Y1 - 2010 A1 - Navlakha, S. A1 - Kingsford, Carl JA - Proceedings of the PSB Pacific Symposium on Biocomputing VL - 15 ER - TY - JOUR T1 - Finding Biologically Accurate Clusterings in Hierarchical Tree Decompositions Using the Variation of Information JF - Journal of Computational BiologyJournal of Computational Biology Y1 - 2010 A1 - Navlakha, Saket A1 - White, James A1 - Nagarajan, Niranjan A1 - M. Pop A1 - Kingsford, Carl AB - Hierarchical clustering is a popular method for grouping together similar elements based on a distance measure between them. In many cases, annotations for some elements are known beforehand, which can aid the clustering process. We present a novel approach for decomposing a hierarchical clustering into the clusters that optimally match a set of known annotations, as measured by the variation of information metric. Our approach is general and does not require the user to enter the number of clusters desired. We apply it to two biological domains: finding protein complexes within protein interaction networks and identifying species within metagenomic DNA samples. For these two applications, we test the quality of our clusters by using them to predict complex and species membership, respectively. We find that our approach generally outperforms the commonly used heuristic methods. VL - 17 SN - 1066-5277, 1557-8666 ER - TY - JOUR T1 - Finishing genomes with limited resources: lessons from an ensemble of microbial genomes JF - BMC GenomicsBMC Genomics Y1 - 2010 A1 - Nagarajan, Niranjan A1 - Cook, Christopher A1 - Di Bonaventura, Maria Pia A1 - Ge, Hong A1 - Richards, Allen A1 - Bishop-Lilly, Kimberly A. A1 - DeSalle, Robert A1 - Read, Timothy D. A1 - M. Pop AB - While new sequencing technologies have ushered in an era where microbial genomes can be easily sequenced, the goal of routinely producing high-quality draft and finished genomes in a cost-effective fashion has still remained elusive. Due to shorter read lengths and limitations in library construction protocols, shotgun sequencing and assembly based on these technologies often results in fragmented assemblies. Correspondingly, while draft assemblies can be obtained in days, finishing can take many months and hence the time and effort can only be justified for high-priority genomes and in large sequencing centers. In this work, we revisit this issue in light of our own experience in producing finished and nearly-finished genomes for a range of microbial species in a small-lab setting. These genomes were finished with surprisingly little investments in terms of time, computational effort and lab work, suggesting that the increased access to sequencing might also eventually lead to a greater proportion of finished genomes from small labs and genomics cores. VL - 11 SN - 1471-2164 ER - TY - JOUR T1 - Genetic and Physiological Activation of Osmosensitive Gene Expression Mimics Transcriptional Signatures of Pathogen Infection in C. elegans JF - PLoS ONEPLoS One Y1 - 2010 A1 - Rohlfing, Anne-Katrin A1 - Miteva, Yana A1 - Sridhar Hannenhalli A1 - Lamitina, Todd AB - The soil-dwelling nematode C. elegans is a powerful system for comparative molecular analyses of environmental stress response mechanisms. Infection of worms with bacterial and fungal pathogens causes the activation of well-characterized innate immune transcriptional programs in pathogen-exposed hypodermal and intestinal tissues. However, the pathophysiological events that drive such transcriptional responses are not understood. Here, we show that infection-activated transcriptional responses are, in large part, recapitulated by either physiological or genetic activation of the osmotic stress response. Microarray profiling of wild type worms exposed to non-lethal hypertonicity identified a suite of genes that were also regulated by infection. Expression profiles of five different osmotic stress resistant (osr) mutants under isotonic conditions reiterated the wild type transcriptional response to osmotic stress and also showed substantial similarity to infection-induced gene expression under isotonic conditions. Computational, transgenic, and functional approaches revealed that two GATA transcription factors previously implicated in infection-induced transcriptional responses, elt-2 and elt-3, are also essential for coordinated tissue-specific activation of osmosensitive gene expression and promote survival under osmotically stressful conditions. Together, our data suggest infection and osmotic adaptation share previously unappreciated transcriptional similarities which might be controlled via regulation of tissue-specific GATA transcription factors. VL - 5 ER - TY - CHAP T1 - Genetics of Trypanosoma cruzi in American Trypanosomiasis: Chagas Disease One hundred Years of Research Y1 - 2010 A1 - Bartholomeu, D. A1 - Buck, G. A1 - Teixeira, S. A1 - El-Sayed, N.M. PB - Elsevier Press CY - Burlington ER - TY - JOUR T1 - Genome Sequence of Hybrid Vibrio Cholerae O1 MJ-1236, B-33, and CIRS101 and Comparative Genomics with V. Cholerae JF - Journal of BacteriologyJ. Bacteriol.Journal of BacteriologyJ. Bacteriol. Y1 - 2010 A1 - Grim, Christopher J. A1 - Hasan, Nur A. A1 - Taviani, Elisa A1 - Haley, Bradd A1 - Jongsik, Chun A1 - Brettin, Thomas S. A1 - Bruce, David C. A1 - Detter, J. Chris A1 - Han, Cliff S. A1 - Chertkov, Olga A1 - Challacombe, Jean A1 - Huq, Anwar A1 - Nair, G. Balakrish A1 - Rita R. Colwell AB - The genomes of Vibrio cholerae O1 Matlab variant MJ-1236, Mozambique O1 El Tor variant B33, and altered O1 El Tor CIRS101 were sequenced. All three strains were found to belong to the phylocore group 1 clade of V. cholerae, which includes the 7th-pandemic O1 El Tor and serogroup O139 isolates, despite displaying certain characteristics of the classical biotype. All three strains were found to harbor a hybrid variant of CTXΦ and an integrative conjugative element (ICE), leading to their establishment as successful clinical clones and the displacement of prototypical O1 El Tor. The absence of strain- and group-specific genomic islands, some of which appear to be prophages and phage-like elements, seems to be the most likely factor in the recent establishment of dominance of V. cholerae CIRS101 over the other two hybrid strains. VL - 192 SN - 0021-9193, 1098-5530 ER - TY - JOUR T1 - Genome-wide analysis reveals novel genes essential for heme homeostasis in Caenorhabditis elegans. JF - PLoS Genet Y1 - 2010 A1 - Severance, Scott A1 - Rajagopal, Abbhirami A1 - Rao, Anita U A1 - Cerqueira, Gustavo C A1 - Mitreva, Makedonka A1 - El-Sayed, Najib M A1 - Krause, Michael A1 - Hamza, Iqbal KW - Animals KW - Caenorhabditis elegans KW - Dose-Response Relationship, Drug KW - Gene Expression Profiling KW - Gene Expression Regulation KW - genes KW - Genome-Wide Association Study KW - Heme KW - Homeostasis KW - HUMANS KW - Leishmania KW - Nematoda KW - Trypanosoma AB -

Heme is a cofactor in proteins that function in almost all sub-cellular compartments and in many diverse biological processes. Heme is produced by a conserved biosynthetic pathway that is highly regulated to prevent the accumulation of heme--a cytotoxic, hydrophobic tetrapyrrole. Caenorhabditis elegans and related parasitic nematodes do not synthesize heme, but instead require environmental heme to grow and develop. Heme homeostasis in these auxotrophs is, therefore, regulated in accordance with available dietary heme. We have capitalized on this auxotrophy in C. elegans to study gene expression changes associated with precisely controlled dietary heme concentrations. RNA was isolated from cultures containing 4, 20, or 500 microM heme; derived cDNA probes were hybridized to Affymetrix C. elegans expression arrays. We identified 288 heme-responsive genes (hrgs) that were differentially expressed under these conditions. Of these genes, 42% had putative homologs in humans, while genomes of medically relevant heme auxotrophs revealed homologs for 12% in both Trypanosoma and Leishmania and 24% in parasitic nematodes. Depletion of each of the 288 hrgs by RNA-mediated interference (RNAi) in a transgenic heme-sensor worm strain identified six genes that regulated heme homeostasis. In addition, seven membrane-spanning transporters involved in heme uptake were identified by RNAi knockdown studies using a toxic heme analog. Comparison of genes that were positive in both of the RNAi screens resulted in the identification of three genes in common that were vital for organismal heme homeostasis in C. elegans. Collectively, our results provide a catalog of genes that are essential for metazoan heme homeostasis and demonstrate the power of C. elegans as a genetic animal model to dissect the regulatory circuits which mediate heme trafficking in both vertebrate hosts and their parasites, which depend on environmental heme for survival.

VL - 6 CP - 7 M3 - 10.1371/journal.pgen.1001044 ER - TY - JOUR T1 - Genomic characterization of the Yersinia genus JF - Genome BiologyGenome Biology Y1 - 2010 A1 - Chen, Peter E. A1 - Cook, Christopher A1 - Stewart, Andrew C. A1 - Nagarajan, Niranjan A1 - Sommer, Dan D. A1 - M. Pop A1 - Thomason, Brendan A1 - Thomason, Maureen P. K. A1 - Lentz, Shannon A1 - Nolan, Nichole A1 - Sozhamannan, Shanmuga A1 - Sulakvelidze, Alexander A1 - Mateczun, Alfred A1 - Du, Lei A1 - Zwick, Michael E. A1 - Read, Timothy D. AB - New DNA sequencing technologies have enabled detailed comparative genomic analyses of entire genera of bacterial pathogens. Prior to this study, three species of the enterobacterial genus Yersinia that cause invasive human diseases (Yersinia pestis, Yersinia pseudotuberculosis, and Yersinia enterocolitica) had been sequenced. However, there were no genomic data on the Yersinia species with more limited virulence potential, frequently found in soil and water environments. VL - 11 SN - 1465-6906 ER - TY - JOUR T1 - Hopx and Hdac2 Interact to Modulate Gata4 Acetylation and Embryonic Cardiac Myocyte Proliferation JF - Developmental CellDevelopmental Cell Y1 - 2010 A1 - Trivedi, Chinmay M. A1 - Zhu, Wenting A1 - Wang, Qiaohong A1 - Jia, Cheng A1 - Kee, Hae Jin A1 - Li, Li A1 - Sridhar Hannenhalli A1 - Epstein, Jonathan A. AB - SummaryRegulation of chromatin structure via histone modification has recently received intense attention. Here, we demonstrate that the chromatin-modifying enzyme histone deacetylase 2 (Hdac2) functions with a small homeodomain factor, Hopx, to mediate deacetylation of Gata4, which is expressed by cardiac progenitor cells and plays critical roles in the regulation of cardiogenesis. In the absence of Hopx and Hdac2 in mouse embryos, Gata4 hyperacetylation is associated with a marked increase in cardiac myocyte proliferation, upregulation of Gata4 target genes, and perinatal lethality. Hdac2 physically interacts with Gata4, and this interaction is stabilized by Hopx. The ability of Gata4 to transactivate cell cycle genes is impaired by Hopx/Hdac2-mediated deacetylation, and this effect is abrogated by loss of Hdac2-Gata4 interaction. These results suggest that Gata4 is a nonhistone target of Hdac2-mediated deacetylation and that Hdac2, Hopx, and Gata4 coordinately regulate cardiac myocyte proliferation during embryonic development. VL - 19 SN - 1534-5807 ER - TY - JOUR T1 - Identification of Pathogenic Vibrio Species by Multilocus PCR-Electrospray Ionization Mass Spectrometry and Its Application to Aquatic Environments of the Former Soviet Republic of Georgia JF - Applied and Environmental MicrobiologyAppl. Environ. Microbiol.Applied and Environmental MicrobiologyAppl. Environ. Microbiol. Y1 - 2010 A1 - Whitehouse, Chris A. A1 - Baldwin, Carson A1 - Sampath, Rangarajan A1 - Blyn, Lawrence B. A1 - Melton, Rachael A1 - Li, Feng A1 - Hall, Thomas A. A1 - Harpin, Vanessa A1 - Matthews, Heather A1 - Tediashvili, Marina A1 - Jaiani, Ekaterina A1 - Kokashvili, Tamar A1 - Janelidze, Nino A1 - Grim, Christopher A1 - Rita R. Colwell A1 - Huq, Anwar AB - The Ibis T5000 is a novel diagnostic platform that couples PCR and mass spectrometry. In this study, we developed an assay that can identify all known pathogenic Vibrio species and field-tested it using natural water samples from both freshwater lakes and the Georgian coastal zone of the Black Sea. Of the 278 total water samples screened, 9 different Vibrio species were detected, 114 (41%) samples were positive for V. cholerae, and 5 (0.8%) samples were positive for the cholera toxin A gene (ctxA). All ctxA-positive samples were from two freshwater lakes, and no ctxA-positive samples from any of the Black Sea sites were detected. VL - 76 SN - 0099-2240, 1098-5336 ER - TY - CHAP T1 - Identifying Differentially Abundant Metabolic Pathways in Metagenomic Datasets T2 - Bioinformatics Research and ApplicationsBioinformatics Research and Applications Y1 - 2010 A1 - Liu, Bo A1 - M. Pop ED - Borodovsky, Mark ED - Gogarten, Johann ED - Przytycka, Teresa ED - Rajasekaran, Sanguthevar AB - Enabled by rapid advances in sequencing technology, metagenomic studies aim to characterize entire communities of microbes bypassing the need for culturing individual bacterial members. One major goal of such studies is to identify specific functional adaptations of microbial communities to their habitats. Here we describe a powerful analytical method (MetaPath) that can identify differentially abundant pathways in metagenomic data-sets, relying on a combination of metagenomic sequence data and prior metabolic pathway knowledge. We show that MetaPath outperforms other common approaches when evaluated on simulated datasets. We also demonstrate the power of our methods in analyzing two, publicly available, metagenomic datasets: a comparison of the gut microbiome of obese and lean twins; and a comparison of the gut microbiome of infant and adult subjects. We demonstrate that the subpathways identified by our method provide valuable insights into the biological activities of the microbiome. JA - Bioinformatics Research and ApplicationsBioinformatics Research and Applications T3 - Lecture Notes in Computer Science PB - Springer Berlin / Heidelberg VL - 6053 SN - 978-3-642-13077-9 ER - TY - JOUR T1 - Intensity normalization improves color calling in SOLiD sequencing JF - Nat MethNat MethNat MethNat Meth Y1 - 2010 A1 - Wu, Hao A1 - Irizarry, Rafael A. A1 - Héctor Corrada Bravo VL - 7 SN - 1548-7091 ER - TY - Generic T1 - MetaPhyler: Taxonomic profiling for metagenomic sequences T2 - 2010 IEEE International Conference on Bioinformatics and Biomedicine (BIBM) Y1 - 2010 A1 - Liu, Bo A1 - Gibbons, T. A1 - Ghodsi, M. A1 - M. Pop KW - Bioinformatics KW - CARMA comparison KW - Databases KW - Genomics KW - Linear regression KW - marker genes KW - matching length KW - Megan comparison KW - metagenomic sequences KW - metagenomics KW - MetaPhyler KW - microbial diversity KW - microorganisms KW - molecular biophysics KW - molecular configurations KW - Pattern classification KW - pattern matching KW - phylogenetic classification KW - Phylogeny KW - PhymmBL comparison KW - reference gene database KW - Sensitivity KW - sequence matching KW - taxonomic classifier KW - taxonomic level KW - taxonomic profiling KW - whole metagenome sequencing data AB - A major goal of metagenomics is to characterize the microbial diversity of an environment. The most popular approach relies on 16S rRNA sequencing, however this approach can generate biased estimates due to differences in the copy number of the 16S rRNA gene between even closely related organisms, and due to PCR artifacts. The taxonomic composition can also be determined from whole-metagenome sequencing data by matching individual sequences against a database of reference genes. One major limitation of prior methods used for this purpose is the use of a universal classification threshold for all genes at all taxonomic levels. We propose that better classification results can be obtained by tuning the taxonomic classifier to each matching length, reference gene, and taxonomic level. We present a novel taxonomic profiler MetaPhyler, which uses marker genes as a taxonomic reference. Results on simulated datasets demonstrate that MetaPhyler outperforms other tools commonly used in this context (CARMA, Megan and PhymmBL). We also present interesting results obtained by applying MetaPhyler to a real metagenomic dataset. JA - 2010 IEEE International Conference on Bioinformatics and Biomedicine (BIBM) PB - IEEE SN - 978-1-4244-8306-8 ER - TY - JOUR T1 - Mimosa: Mixture model of co-expression to detect modulators of regulatory interaction JF - Algorithms for Molecular BiologyAlgorithms for Molecular Biology Y1 - 2010 A1 - Hansen, Matthew A1 - Everett, Logan A1 - Singh, Larry A1 - Sridhar Hannenhalli AB - Functionally related genes tend to be correlated in their expression patterns across multiple conditions and/or tissue-types. Thus co-expression networks are often used to investigate functional groups of genes. In particular, when one of the genes is a transcription factor (TF), the co-expression-based interaction is interpreted, with caution, as a direct regulatory interaction. However, any particular TF, and more importantly, any particular regulatory interaction, is likely to be active only in a subset of experimental conditions. Moreover, the subset of expression samples where the regulatory interaction holds may be marked by presence or absence of a modifier gene, such as an enzyme that post-translationally modifies the TF. Such subtlety of regulatory interactions is overlooked when one computes an overall expression correlation. VL - 5 SN - 1748-7188 ER - TY - JOUR T1 - A model for using a concept inventory as a tool for students' assessment and faculty professional development. JF - CBE Life Sci Educ Y1 - 2010 A1 - Marbach-Ad, Gili A1 - McAdams, Katherine C A1 - Benson, Spencer A1 - Briken, Volker A1 - Cathcart, Laura A1 - Chase, Michael A1 - El-Sayed, Najib M A1 - Frauwirth, Kenneth A1 - Fredericksen, Brenda A1 - Joseph, Sam W A1 - Lee, Vincent A1 - McIver, Kevin S A1 - Mosser, David A1 - Quimby, B Booth A1 - Shields, Patricia A1 - Song, Wenxia A1 - Stein, Daniel C A1 - Stewart, Richard A1 - Thompson, Katerina V A1 - Smith, Ann C KW - Curriculum KW - Faculty KW - Models, Theoretical KW - Research KW - Students KW - Teaching AB -

This essay describes how the use of a concept inventory has enhanced professional development and curriculum reform efforts of a faculty teaching community. The Host Pathogen Interactions (HPI) teaching team is composed of research and teaching faculty with expertise in HPI who share the goal of improving the learning experience of students in nine linked undergraduate microbiology courses. To support evidence-based curriculum reform, we administered our HPI Concept Inventory as a pre- and postsurvey to approximately 400 students each year since 2006. The resulting data include student scores as well as their open-ended explanations for distractor choices. The data have enabled us to address curriculum reform goals of 1) reconciling student learning with our expectations, 2) correlating student learning with background variables, 3) understanding student learning across institutions, 4) measuring the effect of teaching techniques on student learning, and 5) demonstrating how our courses collectively form a learning progression. The analysis of the concept inventory data has anchored and deepened the team's discussions of student learning. Reading and discussing students' responses revealed the gap between our understanding and the students' understanding. We provide evidence to support the concept inventory as a tool for assessing student understanding of HPI concepts and faculty development.

VL - 9 CP - 4 M3 - 10.1187/cbe.10-05-0069 ER - TY - JOUR T1 - Model-Based Quality Assessment and Base-Calling for Second-Generation Sequencing Data JF - Biometrics Y1 - 2010 A1 - Bravo, Héctor Corrada A1 - Irizarry, Rafael A. VL - 66 UR - http://doi.wiley.com/10.1111/j.1541-0420.2009.01353.xhttps://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Fj.1541-0420.2009.01353.x CP - 3 M3 - 10.1111/j.1541-0420.2009.01353.x ER - TY - JOUR T1 - Occurrence of the Vibrio cholerae seventh pandemic VSP-I island and a new variant JF - OMICS: A Journal of Integrative BiologyOMICS: A Journal of Integrative Biology Y1 - 2010 A1 - Grim, Christopher J. A1 - Choi, Jinna A1 - Jongsik, Chun A1 - Jeon, Yoon-Seong A1 - Taviani, Elisa A1 - Hasan, Nur A. A1 - Haley, Bradd A1 - Huq, Anwar A1 - Rita R. Colwell VL - 14 SN - 1536-2310, 1557-8100 ER - TY - JOUR T1 - Overcoming bias and systematic errors in next generation sequencing data JF - Genome medicineGenome medicine Y1 - 2010 A1 - Taub, Margaret A. A1 - Héctor Corrada Bravo A1 - Irizarry, Rafael A. AB - Considerable time and effort has been spent in developing analysis and quality assessment methods to allow the use of microarrays in a clinical setting. As is the case for microarrays and other high-throughput technologies, data from new high-throughput sequencing technologies are subject to technological and biological biases and systematic errors that can impact downstream analyses. Only when these issues can be readily identified and reliably adjusted for will clinical applications of these new technologies be feasible. Although much work remains to be done in this area, we describe consistently observed biases that should be taken into account when analyzing high-throughput sequencing data. In this article, we review current knowledge about these biases, discuss their impact on analysis results, and propose solutions. VL - 2 N1 - http://www.ncbi.nlm.nih.gov/pubmed/21144010?dopt=Abstract ER - TY - JOUR T1 - The power of protein interaction networks for associating genes with diseases JF - BioinformaticsBioinformatics Y1 - 2010 A1 - Navlakha, S. A1 - Kingsford, Carl VL - 26 ER - TY - JOUR T1 - The pre‐seventh pandemic Vibrio cholerae BX 330286 El Tor genome: evidence for the environment as a genome reservoir JF - Environmental Microbiology ReportsEnvironmental Microbiology Reports Y1 - 2010 A1 - Haley, Bradd J. A1 - Grim, Christopher J. A1 - Hasan, Nur A. A1 - Taviani, Elisa A1 - Jongsik, Chun A1 - Brettin, Thomas S. A1 - Bruce, David C. A1 - Challacombe, Jean F. A1 - Detter, J. Chris A1 - Han, Cliff S. A1 - Huq, Anwar A1 - Nair, G. Balakrish A1 - Rita R. Colwell AB - Vibrio cholerae O1 El Tor BX 330286 was isolated from a water sample in Australia in 1986, 9 years after an indigenous outbreak of cholera occurred in that region. This environmental strain encodes virulence factors highly similar to those of clinical strains, suggesting an ability to cause disease in humans. We demonstrate its high similarity in gene content and genome-wide nucleotide sequence to clinical V. cholerae strains, notably to pre-seventh pandemic O1 El Tor strains isolated in 1910 (V. cholerae NCTC 8457) and 1937 (V. cholerae MAK 757), as well as seventh pandemic strains isolated after 1960 globally. Here we demonstrate that this strain represents a transitory clone with shared characteristics between pre-seventh and seventh pandemic strains of V. cholerae. Interestingly, this strain was isolated 25 years after the beginning of the seventh pandemic, suggesting the environment as a genome reservoir in areas where cholera does not occur in sporadic, endemic or epidemic form. VL - 2 SN - 1758-2229 ER - TY - JOUR T1 - Regulating the regulators: modulators of transcription factor activity JF - Methods Mol. BiolMethods Mol. Biol Y1 - 2010 A1 - Everett, L. A1 - Hansen, M. A1 - Sridhar Hannenhalli PB - Springer VL - 674 ER - TY - JOUR T1 - Saliency Guided Summarization of Molecular Dynamics Simulations JF - Scientific Visualization: Advanced ConceptsScientific Visualization: Advanced Concepts Y1 - 2010 A1 - Patro, R. A1 - Ip, C. Y. A1 - Varshney, Amitabh A1 - Hagen, H. AB - We present a novel method to measure saliency in molecular dynamics simulation data. This saliency measure is based on a multiscale center-surround mechanism, which is fast and efficient to compute. We explore the use of the saliency function to guide the selection of representative and anomalous timesteps for summarization of simulations. To this end, we also introduce a multiscale keyframe selection procedure which automatically provides keyframes representing the simulation at varying levels of coarseness. We compare our saliency guided keyframe approach against other methods, and show that it consistently selects superior keyframes as measured by their predictive power in reconstructing the simulation. VL - 1 ER - TY - JOUR T1 - Sequencing and genome assembly using next-generation technologies JF - Methods Mol. BiolMethods Mol. Biol Y1 - 2010 A1 - Nagarajan, N. A1 - M. Pop PB - Springer VL - 673 ER - TY - JOUR T1 - Serodiversity and ecological distribution of Vibrio parahaemolyticus in the Venetian Lagoon, Northeast Italy JF - Environmental Microbiology ReportsEnvironmental Microbiology Reports Y1 - 2010 A1 - Caburlotto, Greta A1 - Haley, Bradd J. A1 - Lleò, Maria M. A1 - Huq, Anwar A1 - Rita R. Colwell AB - Vibrio parahaemolyticus is a natural inhabitant of estuarine and marine environments constituting part of the autochthonous microflora. This species is associated with human gastroenteritis caused by ingestion of contaminated water and undercooked seafood. During the past several years, the number of V. parahaemolyticus gastroenteritis cases have increased worldwide, causing over half of all food-poisoning outbreaks of bacterial origin. Vibrio populations in water are known to be influenced by environmental factors. Notably, it has been shown that in different parts of the world the distribution of V. parahaemolyticus in the marine environment is related to the water temperature. In this study, we identified environmental determinants affecting distribution of V. parahaemolyticus in the Venetian Lagoon, in the Italian North Adriatic Sea. Data obtained revealed that sea surface temperature constitutes the key factor influencing occurrence of V. parahaemolyticus, but salinity and chlorophyll concentration are also important. Serotyping of a collection of V. parahaemolyticus environmental isolates revealed high serodiversity, with serotypes O3:KUT and O1:KUT, belonging to the ‘pandemic group’, occurring with higher frequency. From our results, we conclude that there is no correlation between serotype and specific geographic site or season of the year. However, certain serotypes were isolated in the Lagoon during the entire 18 months of the study, strongly suggesting persistence in this environment. VL - 2 SN - 1758-2229 ER - TY - JOUR T1 - Sites Inferred by Metabolic Background Assertion Labeling (SIMBAL): adapting the Partial Phylogenetic Profiling algorithm to scan sequences for signatures that predict protein function. JF - BMC Bioinformatics Y1 - 2010 A1 - Selengut, Jeremy D A1 - Rusch, Douglas B A1 - Haft, Daniel H KW - algorithms KW - Amino Acid Sequence KW - Gene Expression Profiling KW - Molecular Sequence Data KW - Phylogeny KW - Proteins KW - Sequence Analysis, Protein KW - Structure-Activity Relationship AB -

BACKGROUND: Comparative genomics methods such as phylogenetic profiling can mine powerful inferences from inherently noisy biological data sets. We introduce Sites Inferred by Metabolic Background Assertion Labeling (SIMBAL), a method that applies the Partial Phylogenetic Profiling (PPP) approach locally within a protein sequence to discover short sequence signatures associated with functional sites. The approach is based on the basic scoring mechanism employed by PPP, namely the use of binomial distribution statistics to optimize sequence similarity cutoffs during searches of partitioned training sets.

RESULTS: Here we illustrate and validate the ability of the SIMBAL method to find functionally relevant short sequence signatures by application to two well-characterized protein families. In the first example, we partitioned a family of ABC permeases using a metabolic background property (urea utilization). Thus, the TRUE set for this family comprised members whose genome of origin encoded a urea utilization system. By moving a sliding window across the sequence of a permease, and searching each subsequence in turn against the full set of partitioned proteins, the method found which local sequence signatures best correlated with the urea utilization trait. Mapping of SIMBAL "hot spots" onto crystal structures of homologous permeases reveals that the significant sites are gating determinants on the cytosolic face rather than, say, docking sites for the substrate-binding protein on the extracellular face. In the second example, we partitioned a protein methyltransferase family using gene proximity as a criterion. In this case, the TRUE set comprised those methyltransferases encoded near the gene for the substrate RF-1. SIMBAL identifies sequence regions that map onto the substrate-binding interface while ignoring regions involved in the methyltransferase reaction mechanism in general. Neither method for training set construction requires any prior experimental characterization.

CONCLUSIONS: SIMBAL shows that, in functionally divergent protein families, selected short sequences often significantly outperform their full-length parent sequence for making functional predictions by sequence similarity, suggesting avenues for improved functional classifiers. When combined with structural data, SIMBAL affords the ability to localize and model functional sites.

VL - 11 M3 - 10.1186/1471-2105-11-52 ER - TY - JOUR T1 - Sites Inferred by Metabolic Background Assertion Labeling (SIMBAL): adapting the Partial Phylogenetic Profiling algorithm to scan sequences for signatures that predict protein function JF - BMC bioinformaticsBMC Bioinformatics Y1 - 2010 A1 - J. Selengut A1 - Rusch, Douglas B. A1 - Haft, Daniel H. KW - algorithms KW - Amino Acid Sequence KW - Gene Expression Profiling KW - Molecular Sequence Data KW - Phylogeny KW - Proteins KW - Sequence Analysis, Protein KW - Structure-Activity Relationship AB - BACKGROUND: Comparative genomics methods such as phylogenetic profiling can mine powerful inferences from inherently noisy biological data sets. We introduce Sites Inferred by Metabolic Background Assertion Labeling (SIMBAL), a method that applies the Partial Phylogenetic Profiling (PPP) approach locally within a protein sequence to discover short sequence signatures associated with functional sites. The approach is based on the basic scoring mechanism employed by PPP, namely the use of binomial distribution statistics to optimize sequence similarity cutoffs during searches of partitioned training sets. RESULTS: Here we illustrate and validate the ability of the SIMBAL method to find functionally relevant short sequence signatures by application to two well-characterized protein families. In the first example, we partitioned a family of ABC permeases using a metabolic background property (urea utilization). Thus, the TRUE set for this family comprised members whose genome of origin encoded a urea utilization system. By moving a sliding window across the sequence of a permease, and searching each subsequence in turn against the full set of partitioned proteins, the method found which local sequence signatures best correlated with the urea utilization trait. Mapping of SIMBAL "hot spots" onto crystal structures of homologous permeases reveals that the significant sites are gating determinants on the cytosolic face rather than, say, docking sites for the substrate-binding protein on the extracellular face. In the second example, we partitioned a protein methyltransferase family using gene proximity as a criterion. In this case, the TRUE set comprised those methyltransferases encoded near the gene for the substrate RF-1. SIMBAL identifies sequence regions that map onto the substrate-binding interface while ignoring regions involved in the methyltransferase reaction mechanism in general. Neither method for training set construction requires any prior experimental characterization. CONCLUSIONS: SIMBAL shows that, in functionally divergent protein families, selected short sequences often significantly outperform their full-length parent sequence for making functional predictions by sequence similarity, suggesting avenues for improved functional classifiers. When combined with structural data, SIMBAL affords the ability to localize and model functional sites. VL - 11 N1 - http://www.ncbi.nlm.nih.gov/pubmed/20102603?dopt=Abstract ER - TY - JOUR T1 - Tackling the widespread and critical impact of batch effects in high-throughput data JF - Nature reviews. GeneticsNature reviews. Genetics Y1 - 2010 A1 - Leek, Jeffrey T. A1 - Scharpf, Robert B. A1 - Héctor Corrada Bravo A1 - Simcha, David A1 - Langmead, Benjamin A1 - Johnson, W. Evan A1 - Geman, Donald A1 - Baggerly, Keith A1 - Irizarry, Rafael A. KW - biotechnology KW - Computational Biology KW - Genomics KW - Oligonucleotide Array Sequence Analysis KW - Periodicals as Topic KW - Research Design KW - Sequence Analysis, DNA AB - High-throughput technologies are widely used, for example to assay genetic variants, gene and protein expression, and epigenetic modifications. One often overlooked complication with such studies is batch effects, which occur because measurements are affected by laboratory conditions, reagent lots and personnel differences. This becomes a major problem when batch effects are correlated with an outcome of interest and lead to incorrect conclusions. Using both published studies and our own analyses, we argue that batch effects (as well as other technical and biological artefacts) are widespread and critical to address. We review experimental and computational approaches for doing so. VL - 11 N1 - http://www.ncbi.nlm.nih.gov/pubmed/20838408?dopt=Abstract ER - TY - JOUR T1 - Unexpected abundance of coenzyme F(420)-dependent enzymes in Mycobacterium tuberculosis and other actinobacteria JF - Journal of bacteriologyJournal of bacteriology Y1 - 2010 A1 - J. Selengut A1 - Haft, Daniel H. KW - Actinobacteria KW - Amino Acid Sequence KW - Binding Sites KW - Coenzymes KW - Flavonoids KW - Gene Expression Profiling KW - Gene Expression Regulation, Bacterial KW - Genome, Bacterial KW - molecular biology KW - Molecular Sequence Data KW - Molecular Structure KW - Mycobacterium tuberculosis KW - Phylogeny KW - Protein Conformation KW - Riboflavin AB - Regimens targeting Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), require long courses of treatment and a combination of three or more drugs. An increase in drug-resistant strains of M. tuberculosis demonstrates the need for additional TB-specific drugs. A notable feature of M. tuberculosis is coenzyme F(420), which is distributed sporadically and sparsely among prokaryotes. This distribution allows for comparative genomics-based investigations. Phylogenetic profiling (comparison of differential gene content) based on F(420) biosynthesis nominated many actinobacterial proteins as candidate F(420)-dependent enzymes. Three such families dominated the results: the luciferase-like monooxygenase (LLM), pyridoxamine 5'-phosphate oxidase (PPOX), and deazaflavin-dependent nitroreductase (DDN) families. The DDN family was determined to be limited to F(420)-producing species. The LLM and PPOX families were observed in F(420)-producing species as well as species lacking F(420) but were particularly numerous in many actinobacterial species, including M. tuberculosis. Partitioning the LLM and PPOX families based on an organism's ability to make F(420) allowed the application of the SIMBAL (sites inferred by metabolic background assertion labeling) profiling method to identify F(420)-correlated subsequences. These regions were found to correspond to flavonoid cofactor binding sites. Significantly, these results showed that M. tuberculosis carries at least 28 separate F(420)-dependent enzymes, most of unknown function, and a paucity of flavin mononucleotide (FMN)-dependent proteins in these families. While prevalent in mycobacteria, markers of F(420) biosynthesis appeared to be absent from the normal human gut flora. These findings suggest that M. tuberculosis relies heavily on coenzyme F(420) for its redox reactions. This dependence and the cofactor's rarity may make F(420)-related proteins promising drug targets. VL - 192 N1 - http://www.ncbi.nlm.nih.gov/pubmed/20675471?dopt=Abstract ER - TY - JOUR T1 - Unexpected abundance of coenzyme F(420)-dependent enzymes in Mycobacterium tuberculosis and other actinobacteria. JF - J Bacteriol Y1 - 2010 A1 - Selengut, Jeremy D A1 - Haft, Daniel H KW - Actinobacteria KW - Amino Acid Sequence KW - Binding Sites KW - Coenzymes KW - Flavonoids KW - Gene Expression Profiling KW - Gene Expression Regulation, Bacterial KW - Genome, Bacterial KW - molecular biology KW - Molecular Sequence Data KW - Molecular Structure KW - Mycobacterium tuberculosis KW - Phylogeny KW - Protein Conformation KW - Riboflavin AB -

Regimens targeting Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), require long courses of treatment and a combination of three or more drugs. An increase in drug-resistant strains of M. tuberculosis demonstrates the need for additional TB-specific drugs. A notable feature of M. tuberculosis is coenzyme F(420), which is distributed sporadically and sparsely among prokaryotes. This distribution allows for comparative genomics-based investigations. Phylogenetic profiling (comparison of differential gene content) based on F(420) biosynthesis nominated many actinobacterial proteins as candidate F(420)-dependent enzymes. Three such families dominated the results: the luciferase-like monooxygenase (LLM), pyridoxamine 5'-phosphate oxidase (PPOX), and deazaflavin-dependent nitroreductase (DDN) families. The DDN family was determined to be limited to F(420)-producing species. The LLM and PPOX families were observed in F(420)-producing species as well as species lacking F(420) but were particularly numerous in many actinobacterial species, including M. tuberculosis. Partitioning the LLM and PPOX families based on an organism's ability to make F(420) allowed the application of the SIMBAL (sites inferred by metabolic background assertion labeling) profiling method to identify F(420)-correlated subsequences. These regions were found to correspond to flavonoid cofactor binding sites. Significantly, these results showed that M. tuberculosis carries at least 28 separate F(420)-dependent enzymes, most of unknown function, and a paucity of flavin mononucleotide (FMN)-dependent proteins in these families. While prevalent in mycobacteria, markers of F(420) biosynthesis appeared to be absent from the normal human gut flora. These findings suggest that M. tuberculosis relies heavily on coenzyme F(420) for its redox reactions. This dependence and the cofactor's rarity may make F(420)-related proteins promising drug targets.

VL - 192 CP - 21 M3 - 10.1128/JB.00425-10 ER - TY - JOUR T1 - Validating the systematic position of ıt Plationus Segers, Murugan & Dumont, 1993 (Rotifera: Brachionidae) using sequences of the large subunit of the nuclear ribosomal DNA and of cytochrome C oxidase JF - HydrobiologiaHydrobiologia Y1 - 2010 A1 - Reyna-Fabian, M. E. A1 - Laclette, J. P. A1 - Michael P. Cummings A1 - García-Varela, M. KW - Cox1 KW - likelihood KW - LSU KW - maximum KW - Phylogeny KW - Plationus AB - Members of the family Brachionidae are free-living organisms that range in size from 170 to 250 microns. They comprise part of the zooplankton in freshwater and marine systems worldwide. Morphologically, members of the family are characterized by a single piece loricated body without furrows, grooves, sulci or dorsal head shields, and a malleate trophi. Differences in these structures have been traditionally used to recognize 217 species that are classified into seven genera. However, the validity of the species, Plationus patulus, P. patulus macracanthus P. polyacanthus, and P. felicitas have been confused because they were alternatively assigned in Brachionus or Platyias, when considering only morphological and ecological characters. Based on scanning electron microscope (SEM) images of the trophi, these taxa were assigned in a new genus, Plationus. In this study, we examined the systematic position of P. patulus and P. patulus macracanthus using DNA sequences of two genes: the cytochrome oxidase subunit 1 (cox1) and domains D2 and D3 of the large subunit of the nuclear ribosomal RNA (LSU). In addition, the cox1 and LSU sequences representing five genera of Brachionidae (Anuraeopsis, Brachionus, Keratella, Plationus, and Platyias) plus four species of three families from the order Ploima were used as the outgroup. The maximum likelihood (ML) analyses were conducted for each individual gene as well as for the combined (cox1 + LSU) data set. The ML tree from the combined data set yielded the family Brachionidae as a monophyletic group with weak bootstrap support (< 50%). Five main clades in this tree had high (> 85%) bootstrap support. The first clade was composed of three populations of P. patulus + P. patulus macracanthus. The second clade was composed of a single species of Platyias. The third clade was composed of six species of Brachionus. The fourth clade included a single species of the genus Anuraeopsis, and the fifth clade was composed of three species of the genus Keratella. The genetic divergence between Plationus and Platyias ranged from 18.4 to 19.2% for cox1, and from 4.5 to 4.9% for LSU, and between Brachionus and Plationus, it ranged from 16.9 to 23.1% (cox1), and from 7.3 to 9.1% (LSU). Morphological evidence, the amount of genetic divergence, the systematic position of Plationus within the family Brachionidae, and the position of Plationus as a sister group of Brachionus and Platyias support the validity of Plationus patulus and P. patulus macracanthus into the genus Plationus. VL - 644 ER - TY - JOUR T1 - Young Proteins Experience More Variable Selection Pressures Than Old Proteins JF - Genome ResearchGenome Res.Genome ResearchGenome Res. Y1 - 2010 A1 - Vishnoi, Anchal A1 - Kryazhimskiy, Sergey A1 - Bazykin, Georgii A. A1 - Sridhar Hannenhalli A1 - Plotkin, Joshua B. AB - It is well known that young proteins tend to experience weaker purifying selection and evolve more quickly than old proteins. Here, we show that, in addition, young proteins tend to experience more variable selection pressures over time than old proteins. We demonstrate this pattern in three independent taxonomic groups: yeast, Drosophila, and mammals. The increased variability of selection pressures on young proteins is highly significant even after controlling for the fact that young proteins are typically shorter and experience weaker purifying selection than old proteins. The majority of our results are consistent with the hypothesis that the function of a young gene tends to change over time more readily than that of an old gene. At the same time, our results may be caused in part by young genes that serve constant functions over time, but nevertheless appear to evolve under changing selection pressures due to depletion of adaptive mutations. In either case, our results imply that the evolution of a protein-coding sequence is partly determined by its age and origin, and not only by the phenotypic properties of the encoded protein. We discuss, via specific examples, the consequences of these findings for understanding of the sources of evolutionary novelty. VL - 20 SN - 1088-9051, 1549-5469 ER - TY - JOUR T1 - 2009 Swine-Origin Influenza A (H1N1) Resembles Previous Influenza Isolates JF - PLoS ONEPLoS ONEPLoS ONEPLoS ONE Y1 - 2009 A1 - Kingsford, Carl A1 - Nagarajan, Niranjan A1 - Salzberg, Steven L. AB - In April 2009, novel swine-origin influenza viruses (S-OIV) were identified in patients from Mexico and the United States. The viruses were genetically characterized as a novel influenza A (H1N1) strain originating in swine, and within a very short time the S-OIV strain spread across the globe via human-to-human contact.We conducted a comprehensive computational search of all available sequences of the surface proteins of H1N1 swine influenza isolates and found that a similar strain to S-OIV appeared in Thailand in 2000. The earlier isolates caused infections in pigs but only one sequenced human case, A/Thailand/271/2005 (H1N1). Differences between the Thai cases and S-OIV may help shed light on the ability of the current outbreak strain to spread rapidly among humans. VL - 4 ER - TY - JOUR T1 - Analysis of clonally related environmental Vibrio cholerae O1 El Tor isolated before 1992 from Varanasi, India reveals origin of SXT‐ICEs belonging to O139 and O1 serogroups JF - Environmental Microbiology ReportsEnvironmental Microbiology Reports Y1 - 2009 A1 - Mohapatra, Saswat S. A1 - Mantri, Chinmay K. A1 - Mohapatra, Harapriya A1 - Rita R. Colwell A1 - Singh, Durg V. AB - In this study, we report the presence of SXT in environmental Vibrio cholerae O1 El Tor strains isolated before 1992 from Varanasi, India. All isolates, except one, were resistant to Tm, and/or Sul, Sm, Fr, Na and Am. None contained plasmids. PCR and DNA sequencing revealed the presence of SXT containing dfrA1 and/or sulII, strAB in six isolates and dfr18, sulII and strAB in five isolates. Three clinical V. cholerae O1 isolated during 1992 contained the antibiotic resistance gene cassette aadA1 in the class 1 integron. Conjugation experiments, followed by PCR analysis of transconjugants, provided evidence of the transferable nature of SXT and associated antibiotic resistance genes, and its integration into the prfC site. Results of phylogenetic analysis of the intSXT gene of clonally similar V. cholerae showed a clear difference between dfr18+ and dfrA1+V. cholerae O1 isolates. This is the first report of the occurrence of SXT harbouring sulII, strAB, dfr18 and/or dfrA1 genes in environmental V. cholerae O1 isolated prior to 1992 from Varanasi, India, and suggests emergence of SXT+ antibiotic-resistant V. cholerae O139 and O1 from an environmental V. cholerae progenitor by acquisition of SXT and antibiotic-resistant gene clusters. VL - 2 SN - 1758-2229 ER - TY - JOUR T1 - ARDB--Antibiotic Resistance Genes Database JF - Nucleic Acids ResearchNucleic Acids Research Y1 - 2009 A1 - Liu, B. A1 - M. Pop AB - The treatment of infections is increasingly compromised by the ability of bacteria to develop resistance to antibiotics through mutations or through the acquisition of resistance genes. Antibiotic resistance genes also have the potential to be used for bio-terror purposes through genetically modified organisms. In order to facilitate the identification and characterization of these genes, we have created a manually curated database—the Antibiotic Resistance Genes Database (ARDB)—unifying most of the publicly available information on antibiotic resistance. Each gene and resistance type is annotated with rich information, including resistance profile, mechanism of action, ontology, COG and CDD annotations, as well as external links to sequence and protein databases. Our database also supports sequence similarity searches and implements an initial version of a tool for characterizing common mutations that confer antibiotic resistance. The information we provide can be used as compendium of antibiotic resistance factors as well as to identify the resistance genes of newly sequenced genes, genomes, or metagenomes. Currently, ARDB contains resistance information for 13 293 genes, 377 types, 257 antibiotics, 632 genomes, 933 species and 124 genera. ARDB is available at http://ardb.cbcb.umd.edu/. VL - 37 SN - 0305-1048, 1362-4962 ER - TY - JOUR T1 - Assessing Student Understanding of Host Pathogen Interactions Using a Concept Inventory JF - J. Microbiol. Biol. Ed. Y1 - 2009 A1 - Marbach-Ad, G. A1 - Briken, V. A1 - El-Sayed, N.M. A1 - Frauwirth, K. A1 - Fredericksen, B. A1 - Hutcheson, S. A1 - Gao, L.-Y. A1 - Joseph, S. A1 - Lee, V. A1 - McIver, K.S. A1 - Mosser, D. A1 - Quimby, B.B. A1 - Shields, P. A1 - Song, W. A1 - Stein, D.C. A1 - Yuan, R.T. A1 - Smith, A.C. VL - 10 ER - TY - JOUR T1 - Automated classification of bird and amphibian calls using machine learning: A comparison of methods JF - Ecological Informatics Y1 - 2009 A1 - Acevedo, Miguel A. A1 - Corrada-Bravo, Carlos J. A1 - Corrada-Bravo, Hector A1 - Villanueva-Rivera, Luis J. A1 - Aide, T. Mitchell VL - 4 UR - http://linkinghub.elsevier.com/retrieve/pii/S1574954109000351http://api.elsevier.com/content/article/PII:S1574954109000351?httpAccept=text/xmlhttp://api.elsevier.com/content/article/PII:S1574954109000351?httpAccept=text/plain CP - 4 J1 - Ecological Informatics M3 - 10.1016/j.ecoinf.2009.06.005 ER - TY - JOUR T1 - Biological agent detection technologies JF - Molecular Ecology ResourcesMolecular Ecology Resources Y1 - 2009 A1 - Jakupciak, John P. A1 - Rita R. Colwell KW - barcoding KW - biological agent KW - DETECTION KW - identification KW - sequencing AB - The challenge for first responders, physicians in the emergency room, public health personnel, as well as for food manufacturers, distributors and retailers is accurate and reliable identification of pathogenic agents and their corresponding diseases. This is the weakest point in biological agent detection capability today.There is intense research for new molecular detection technologies that could be used for very accurate detection of pathogens that would be a concern to first responders. These include the need for sensors for multiple applications as varied as understanding the ecology of pathogenic micro-organisms, forensics, environmental sampling for detect-to-treat applications, biological sensors for ‘detect to warn’ in infrastructure protection, responses to reports of ‘suspicious powders’, and customs and borders enforcement, to cite a few examples. The benefits of accurate detection include saving millions of dollars annually by reducing disruption of the workforce and the national economy and improving delivery of correct countermeasures to those who are most in need of the information to provide protective and/or response measures. VL - 9 SN - 1755-0998 ER - TY - JOUR T1 - Comparative genomics reveals mechanism for short-term and long-term clonal transitions in pandemic Vibrio cholerae JF - Proceedings of the National Academy of SciencesProceedings of the National Academy of Sciences Y1 - 2009 A1 - Chun, J. A1 - Grim, C. J. A1 - Hasan, N. A. A1 - Lee, J. H. A1 - Choi, S. Y. A1 - Haley, B. J. A1 - Taviani, E. A1 - Jeon, Y. S. A1 - Kim, D. W. A1 - Lee, J. H. A1 - Rita R. Colwell AB - Vibrio cholerae, the causative agent of cholera, is a bacterium autochthonous to the aquatic environment, and a serious public health threat. V. cholerae serogroup O1 is responsible for the previous two cholera pandemics, in which classical and El Tor biotypes were dominant in the sixth and the current seventh pandemics, respectively. Cholera researchers continually face newly emerging and reemerging pathogenic clones carrying diverse combinations of phenotypic and genotypic properties, which significantly hampered control of the disease. To elucidate evolutionary mechanisms governing genetic diversity of pandemic V. cholerae, we compared the genome sequences of 23 V. cholerae strains isolated from a variety of sources over the past 98 years. The genome-based phylogeny revealed 12 distinct V. cholerae lineages, of which one comprises both O1 classical and El Tor biotypes. All seventh pandemic clones share nearly identical gene content. Using analogy to influenza virology, we define the transition from sixth to seventh pandemic strains as a “shift” between pathogenic clones belonging to the same O1 serogroup, but from significantly different phyletic lineages. In contrast, transition among clones during the present pandemic period is characterized as a “drift” between clones, differentiated mainly by varying composition of laterally transferred genomic islands, resulting in emergence of variants, exemplified by V. cholerae O139 and V. cholerae O1 El Tor hybrid clones. Based on the comparative genomics it is concluded that V. cholerae undergoes extensive genetic recombination via lateral gene transfer, and, therefore, genome assortment, not serogroup, should be used to define pathogenic V. cholerae clones. VL - 106 SN - 0027-8424, 1091-6490 ER - TY - JOUR T1 - Complete Genome Sequence of Aggregatibacter (Haemophilus) Aphrophilus NJ8700 JF - Journal of BacteriologyJ. Bacteriol.Journal of BacteriologyJ. Bacteriol. Y1 - 2009 A1 - Di Bonaventura, Maria Pia A1 - DeSalle, Rob A1 - M. Pop A1 - Nagarajan, Niranjan A1 - Figurski, David H. A1 - Fine, Daniel H. A1 - Kaplan, Jeffrey B. A1 - Planet, Paul J. AB - We report the finished and annotated genome sequence of Aggregatibacter aphrophilus strain NJ8700, a strain isolated from the oral flora of a healthy individual, and discuss characteristics that may affect its dual roles in human health and disease. This strain has a rough appearance, and its genome contains genes encoding a type VI secretion system and several factors that may participate in host colonization. VL - 191 SN - 0021-9193, 1098-5530 ER - TY - Generic T1 - A cooperative combinatorial Particle Swarm Optimization algorithm for side-chain packing T2 - IEEE Swarm Intelligence Symposium, 2009. SIS '09 Y1 - 2009 A1 - Lapizco-Encinas, G. A1 - Kingsford, Carl A1 - Reggia, James A. KW - Algorithm design and analysis KW - Amino acids KW - combinatorial mathematics KW - cooperative combinatorial particle swarm optimization algorithm KW - Design optimization KW - Encoding KW - Feedback KW - numerical optimization KW - Optimization methods KW - particle swarm optimisation KW - Particle swarm optimization KW - Partitioning algorithms KW - Proteins KW - proteomics KW - proteomics optimization KW - Robustness KW - side-chain packing AB - Particle Swarm Optimization (PSO) is a well-known, competitive technique for numerical optimization with real-parameter representation. This paper introduces CCPSO, a new Cooperative Particle Swarm Optimization algorithm for combinatorial problems. The cooperative strategy is achieved by splitting the candidate solution vector into components, where each component is optimized by a particle. Particles move throughout a continuous space, their movements based on the influences exerted by static particles that then get feedback based on the fitness of the candidate solution. Here, the application of this technique to side-chain packing (a proteomics optimization problem) is investigated. To verify the efficiency of the proposed CCPSO algorithm, we test our algorithm on three side-chain packing problems and compare our results with the provably optimal result. Computational results show that the proposed algorithm is very competitive, obtaining a conformation with an energy value within 1% of the provably optimal solution in many proteins. JA - IEEE Swarm Intelligence Symposium, 2009. SIS '09 PB - IEEE SN - 978-1-4244-2762-8 ER - TY - JOUR T1 - CTCF binding site classes exhibit distinct evolutionary, genomic, epigenomic and transcriptomic features JF - Genome BiologyGenome Biology Y1 - 2009 A1 - Essien, Kobby A1 - Vigneau, Sebastien A1 - Apreleva, Sofia A1 - Singh, Larry N. A1 - Bartolomei, Marisa S. A1 - Sridhar Hannenhalli AB - CTCF (CCCTC-binding factor) is an evolutionarily conserved zinc finger protein involved in diverse functions ranging from negative regulation of MYC, to chromatin insulation of the beta-globin gene cluster, to imprinting of the Igf2 locus. The 11 zinc fingers of CTCF are known to differentially contribute to the CTCF-DNA interaction at different binding sites. It is possible that the differences in CTCF-DNA conformation at different binding sites underlie CTCF's functional diversity. If so, the CTCF binding sites may belong to distinct classes, each compatible with a specific functional role. VL - 10 SN - 1465-6906 ER - TY - JOUR T1 - Detection of toxigenic Vibrio cholerae O1 in freshwater lakes of the former Soviet Republic of Georgia JF - Environmental Microbiology ReportsEnvironmental Microbiology Reports Y1 - 2009 A1 - Grim, Christopher J. A1 - Jaiani, Ekaterina A1 - Whitehouse, Chris A. A1 - Janelidze, Nino A1 - Kokashvili, Tamuna A1 - Tediashvili, Marina A1 - Rita R. Colwell A1 - Huq, Anwar AB - Three freshwater lakes, Lisi Lake, Kumisi Lake and Tbilisi Sea, near Tbilisi, Georgia, were studied from January 2006 to December 2007 to determine the presence of Vibrio cholerae employing both bacteriological culture method and direct detection methods, namely PCR and direct fluorescent antibody (DFA). For PCR, DNA extracted from water samples was tested for presence of V. cholerae and genes coding for selected virulence factors. Vibrio cholerae non-O1/non-O139 was routinely isolated by culture from all three lakes; whereas V. cholerae O1 and O139 were not. Water samples collected during the summer months from Lisi Lake and Kumisi Lake were positive for both V. cholerae and V. cholerae ctxA, tcpA, zot, ompU and toxR by PCR. Water samples collected during the same period from both Lisi and Kumisi Lake were also positive for V. cholerae serogroup O1 by DFA. All of the samples were negative for V. cholerae serotype O139. The results of this study provide evidence for an environmental presence of toxigenic V. cholerae O1, which may represent a potential source of illness as these lakes serve as recreational water in Tbilisi, Georgia. VL - 2 SN - 1758-2229 ER - TY - JOUR T1 - Determination of relationships among non-toxigenic Vibrio cholerae O1 biotype El Tor strains from housekeeping gene sequences and ribotype patterns JF - Research in MicrobiologyResearch in Microbiology Y1 - 2009 A1 - Mohapatra, Saswat S. A1 - Ramachandran, Dhanya A1 - Mantri, Chinmay K. A1 - Rita R. Colwell A1 - Singh, Durg V. KW - Housekeeping genes KW - Ribotyping KW - sequencing KW - Vibrio cholerae AB - Sequencing of three housekeeping genes, mdh, dnaE and recA, and ribotyping for seven non-toxigenic Vibrio cholerae O1 strains isolated from different geographic sources indicate a phylogenetic relationship among the strains. Results of MLST and ribotyping indicate a clear difference between three toxigenic strains (N16961, O395, and 569B) and three non-toxigenic strains from India (GS1, GS2, and GW87) and one Guam strain (X392), the latter of which were similar in both MLST and ribotyping, while two other non-toxigenic strains from the USA and India (2740-80 and OR69) appeared to be more closely related to toxigenic strains than to non-toxigenic strains, although this was not supported by ribotyping. These results provide clues to the emergence of toxigenic strains from a non-toxigenic progenitor by acquisition of virulence gene clusters. Results of split decomposition analysis suggest that widespread recombination occurs among the three housekeeping genes and that recombination plays an important role in the emergence of toxigenic strains of V. cholerae O1. VL - 160 SN - 0923-2508 ER - TY - JOUR T1 - Diversity and Seasonality of Bioluminescent Vibrio Cholerae Populations in Chesapeake Bay JF - Applied and Environmental MicrobiologyAppl. Environ. Microbiol.Applied and Environmental MicrobiologyAppl. Environ. Microbiol. Y1 - 2009 A1 - Zo, Young-Gun A1 - Chokesajjawatee, Nipa A1 - Grim, Christopher A1 - Arakawa, Eiji A1 - Watanabe, Haruo A1 - Rita R. Colwell AB - Association of luminescence with phenotypic and genotypic traits and with environmental parameters was determined for 278 strains of Vibrio cholerae isolated from the Chesapeake Bay during 1998 to 2000. Three clusters of luminescent strains (A, B, and C) and two nonluminescent clusters (X and Y) were identified among 180 clonal types. V. cholerae O1 strains isolated during pandemics and endemic cholera in the Ganges Delta were related to cluster Y. Heat-stable enterotoxin (encoded by stn) and the membrane protein associated with bile resistance (encoded by ompU) were found to be linked to luminescence in strains of cluster A. Succession from nonluminescent to luminescent populations of V. cholerae occurred during spring to midsummer. Occurrence of cluster A strains in water with neutral pH was contrasted with that of cluster Y strains in water with a pH of >8. Cluster A was found to be associated with a specific calanoid population cooccurring with cyclopoids. Cluster B was related to cluster Y, with its maximal prevalence at pH 8. Occurrence of cluster B strains was more frequent with warmer water temperatures and negatively correlated with maturity of the copepod community. It is concluded that each cluster of luminescent V. cholerae strains occupies a distinct ecological niche. Since the dynamics of these niche-specific subpopulations are associated with zooplankton community composition, the ecology of luminescent V. cholerae is concluded to be related to its interaction with copepods and related crustacean species. VL - 75 SN - 0099-2240, 1098-5336 ER - TY - JOUR T1 - Estimating Tree-Structured Covariance Matrices via Mixed-Integer Programming JF - J Mach Learn Res Y1 - 2009 A1 - Corrada Bravo, Hector A1 - Wright, Stephen A1 - Eng, Kevin H. A1 - Keles, Sündüz A1 - Wahba, Grace VL - 5 ER - TY - JOUR T1 - Evidence for Coregulation of Myocardial Gene Expression by MEF2 and NFAT in Human Heart FailureCLINICAL PERSPECTIVE JF - Circulation: Cardiovascular GeneticsCirculation: Cardiovascular Genetics Y1 - 2009 A1 - Putt, M. E. A1 - Sridhar Hannenhalli A1 - Lu, Y. A1 - Haines, P. A1 - Chandrupatla, H. R. A1 - Morrisey, E. E. A1 - Margulies, K. B. A1 - Cappola, T. P. PB - Am Heart Assoc VL - 2 ER - TY - JOUR T1 - The evolution of Fox genes and their role in development and disease JF - Nature reviews. GeneticsNat Rev GenetNature reviews. GeneticsNat Rev Genet Y1 - 2009 A1 - Sridhar Hannenhalli A1 - Kaestner, Klaus H. AB - The forkhead box (Fox) family of transcription factors, which originated in unicellular eukaryotes, has expanded over time through multiple duplication events, and sometimes through gene loss, to over 40 members in mammals. Fox genes have evolved to acquire a specialized function in many key biological processes. Mutations in Fox genes have a profound effect on human disease, causing phenotypes as varied as cancer, glaucoma and language disorders. We summarize the salient features of the evolution of the Fox gene family and highlight the diverse contribution of various Fox subfamilies to developmental processes, from organogenesis to speech acquisition. VL - 10 SN - 1471-0056 ER - TY - JOUR T1 - Examining the relative influence of familial, genetic, and environmental covariate information in flexible risk models JF - Proceedings of the National Academy of Sciences Y1 - 2009 A1 - Bravo, H. C. A1 - Lee, K. E. A1 - Klein, B. E. K. A1 - Klein, R. A1 - Iyengar, S. K. A1 - Wahba, G. VL - 106 UR - http://www.pnas.org/cgi/doi/10.1073/pnas.0902906106https://syndication.highwire.org/content/doi/10.1073/pnas.0902906106 CP - 20 J1 - Proceedings of the National Academy of Sciences M3 - 10.1073/pnas.0902906106 ER - TY - JOUR T1 - Extreme polymorphism in a vaccine antigen and risk of clinical malaria: implications for vaccine development JF - Sci Transl MedSci Transl Med Y1 - 2009 A1 - Takala, S. L. A1 - Coulibaly, D. A1 - Thera, M. A. A1 - Batchelor, A. H. A1 - Michael P. Cummings A1 - Escalante, A. A. A1 - Ouattara, A. A1 - Traoré, K. A1 - Niangaly, A. A1 - Djimdé, A. A. A1 - Doumbo, O. K. A1 - Plowe, C. V. AB - Vaccines directed against the blood stages of Plasmodium falciparum malaria are intended to prevent the parasite from invading and replicating within host cells. No blood-stage malaria vaccine has shown clinical efficacy in humans. Most malaria vaccine antigens are parasite surface proteins that have evolved extensive genetic diversity, and this diversity could allow malaria parasites to escape vaccine-induced immunity. We examined the extent and within-host dynamics of genetic diversity in the blood-stage malaria vaccine antigen apical membrane antigen-1 in a longitudinal study in Mali. Two hundred and fourteen unique apical membrane antigen-1 haplotypes were identified among 506 human infections, and amino acid changes near a putative invasion machinery binding site were strongly associated with the development of clinical symptoms, suggesting that these residues may be important to consider in designing polyvalent apical membrane antigen-1 vaccines and in assessing vaccine efficacy in field trials. This extreme diversity may pose a serious obstacle to an effective polyvalent recombinant subunit apical membrane antigen-1 vaccine. VL - 1 ER - TY - JOUR T1 - Finding Biologically Accurate Clusterings in Hierarchical Decompositions Using the Variation of Information JF - Lecture Notes in Computer Science: Research in Computational Molecular BiologyLecture Notes in Computer Science: Research in Computational Molecular Biology Y1 - 2009 A1 - Navlakha, S. A1 - White, J. R. A1 - Nagarajan, N. A1 - M. Pop A1 - Kingsford, Carl VL - 5541 ER - TY - JOUR T1 - Gene Profiling of Human Adipose Tissue During Evoked Inflammation In Vivo JF - DiabetesDiabetesDiabetesDiabetes Y1 - 2009 A1 - Shah, Rachana A1 - Lu, Yun A1 - Hinkle, Christine C. A1 - McGillicuddy, Fiona C. A1 - Kim, Roy A1 - Sridhar Hannenhalli A1 - Cappola, Thomas P. A1 - Heffron, Sean A1 - Wang, XingMei A1 - Mehta, Nehal N. A1 - Putt, Mary A1 - Reilly, Muredach P. AB - OBJECTIVE Adipose inflammation plays a central role in obesity-related metabolic and cardiovascular complications. However, few human adipose-secreted proteins are known to mediate these processes. We hypothesized that microarray mRNA profiling of human adipose during evoked inflammation could identify novel adipocytokines.RESEARCH DESIGN AND METHODS Healthy human volunteers (n = 14) were treated with intravenous endotoxin (3 ng/kg lipopolysaccharide [LPS]) and underwent subcutaneous adipose biopsies before and after LPS. On Affymetrix U133Plus 2.0 arrays, adipose mRNAs modulated >1.5-fold (with P < 0.00001) were selected. SignalP 3.0 and SecretomeP 2.0 identified genes predicted to encode secreted proteins. Of these, 86 candidates were chosen for validation in adipose from an independent human endotoxemia protocol (N = 7, with 0.6 ng/kg LPS) and for exploration of cellular origin in primary human adipocytes and macrophages in vitro. RESULTS Microarray identified 776 adipose genes modulated by LPS; 298 were predicted to be secreted. Of detectable prioritized genes, 82 of 85 (96% [95% CI 90–99]) were upregulated (fold changes >1.0) during the lower-dose (LPS 0.6 ng/kg) validation study and 51 of 85 (59% [49–70]) were induced greater than 1.5-fold. Treatment of primary adipocytes with LPS and macrophage polarization to M1 proinflammatory phenotype increased expression by 1.5-fold for 58 and 73% of detectable genes, respectively. CONCLUSIONS We demonstrate that evoked inflammation of human adipose in vivo modulated expression of multiple genes likely secreted by adipocytes and monocytes. These included established adipocytokines and chemokines implicated in recruitment and activation of lymphocytes, adhesion molecules, antioxidants, and several novel genes with unknown function. Such candidates may represent biomarkers and therapeutic targets for obesity-related complications. VL - 58 SN - 0012-1797, 1939-327X ER - TY - JOUR T1 - Genesis, effects and fates of repeats in prokaryotic genomes JF - FEMS microbiology reviews Y1 - 2009 A1 - Todd Treangen A1 - Abraham, Anne-Laure A1 - Touchon, Marie A1 - Rocha, Eduardo PC VL - 33 ER - TY - JOUR T1 - Genome Assembly Reborn: Recent Computational Challenges JF - Briefings in BioinformaticsBrief BioinformBriefings in BioinformaticsBrief Bioinform Y1 - 2009 A1 - M. Pop KW - genome assembly KW - genome sequencing KW - next generation sequencing technologies AB - Research into genome assembly algorithms has experienced a resurgence due to new challenges created by the development of next generation sequencing technologies. Several genome assemblers have been published in recent years specifically targeted at the new sequence data; however, the ever-changing technological landscape leads to the need for continued research. In addition, the low cost of next generation sequencing data has led to an increased use of sequencing in new settings. For example, the new field of metagenomics relies on large-scale sequencing of entire microbial communities instead of isolate genomes, leading to new computational challenges. In this article, we outline the major algorithmic approaches for genome assembly and describe recent developments in this domain. VL - 10 SN - 1467-5463, 1477-4054 ER - TY - JOUR T1 - Genome assortment, not serogroup, defines Vibrio cholerae pandemic strains JF - NatureNature Y1 - 2009 A1 - Brettin, Thomas S. A1 - Bruce, David C. A1 - Challacombe, Jean F. A1 - Detter, John C. A1 - Han, Cliff S. A1 - Munik, A. C. A1 - Chertkov, Olga A1 - Meincke, Linda A1 - Saunders, Elizabeth A1 - Choi, Seon Y. A1 - Haley, Bradd J. A1 - Taviani, Elisa A1 - Jeon, Yoon-Seong A1 - Kim, Dong Wook A1 - Lee, Jae-Hak A1 - Walters, Ronald A. A1 - Hug, Anwar A1 - Rita R. Colwell KW - 59 KW - CHOLERA KW - genes KW - Genetics KW - GENOTYPE KW - ISLANDS KW - ORIGIN KW - PHENOTYPE KW - PUBLIC HEALTH KW - recombination KW - STRAINS KW - Toxins AB - Vibrio cholerae, the causative agent of cholera, is a bacterium autochthonous to the aquatic environment, and a serious public health threat. V. cholerae serogroup O1 is responsible for the previous two cholera pandemics, in which classical and El Tor biotypes were dominant in the 6th and the current 7th pandemics, respectively. Cholera researchers continually face newly emerging and re-emerging pathogenic clones carrying combinations of new serogroups as well as of phenotypic and genotypic properties. These genotype and phenotype changes have hampered control of the disease. Here we compare the complete genome sequences of 23 strains of V. cholerae isolated from a variety of sources and geographical locations over the past 98 years in an effort to elucidate the evolutionary mechanisms governing genetic diversity and genesis of new pathogenic clones. The genome-based phylogeny revealed 12 distinct V. cholerae phyletic lineages, of which one, designated the V. cholerae core genome (CG), comprises both O1 classical and EI Tor biotypes. All 7th pandemic clones share nearly identical gene content, i.e., the same genome backbone. The transition from 6th to 7th pandemic strains is defined here as a 'shift' between pathogenic clones belonging to the same O1 serogroup, but from significantly different phyletic lineages within the CG clade. In contrast, transition among clones during the present 7th pandemic period can be characterized as a 'drift' between clones, differentiated mainly by varying composition of laterally transferred genomic islands, resulting in emergence of variants, exemplified by V.cholerae serogroup O139 and V.cholerae O1 El Tor hybrid clones that produce cholera toxin of classical biotype. Based on the comprehensive comparative genomics presented in this study it is concluded that V. cholerae undergoes extensive genetic recombination via lateral gene transfer, and, therefore, genome assortment, not serogroup, should be used to define pathogenic V. cholerae clones. ER - TY - JOUR T1 - The genome of the blood fluke Schistosoma mansoni. JF - Nature Y1 - 2009 A1 - Berriman, Matthew A1 - Haas, Brian J A1 - LoVerde, Philip T A1 - Wilson, R Alan A1 - Dillon, Gary P A1 - Cerqueira, Gustavo C A1 - Mashiyama, Susan T A1 - Al-Lazikani, Bissan A1 - Andrade, Luiza F A1 - Ashton, Peter D A1 - Aslett, Martin A A1 - Bartholomeu, Daniella C A1 - Blandin, Gaëlle A1 - Caffrey, Conor R A1 - Coghlan, Avril A1 - Coulson, Richard A1 - Day, Tim A A1 - Delcher, Art A1 - DeMarco, Ricardo A1 - Djikeng, Appolinaire A1 - Eyre, Tina A1 - Gamble, John A A1 - Ghedin, Elodie A1 - Gu, Yong A1 - Hertz-Fowler, Christiane A1 - Hirai, Hirohisha A1 - Hirai, Yuriko A1 - Houston, Robin A1 - Ivens, Alasdair A1 - Johnston, David A A1 - Lacerda, Daniela A1 - Macedo, Camila D A1 - McVeigh, Paul A1 - Ning, Zemin A1 - Oliveira, Guilherme A1 - Overington, John P A1 - Parkhill, Julian A1 - Pertea, Mihaela A1 - Pierce, Raymond J A1 - Protasio, Anna V A1 - Quail, Michael A A1 - Rajandream, Marie-Adèle A1 - Rogers, Jane A1 - Sajid, Mohammed A1 - Salzberg, Steven L A1 - Stanke, Mario A1 - Tivey, Adrian R A1 - White, Owen A1 - Williams, David L A1 - Wortman, Jennifer A1 - Wu, Wenjie A1 - Zamanian, Mostafa A1 - Zerlotini, Adhemar A1 - Fraser-Liggett, Claire M A1 - Barrell, Barclay G A1 - El-Sayed, Najib M KW - Animals KW - Biological Evolution KW - Exons KW - Genes, Helminth KW - Genome, Helminth KW - Host-Parasite Interactions KW - Introns KW - Molecular Sequence Data KW - Physical Chromosome Mapping KW - Schistosoma mansoni KW - Schistosomiasis mansoni AB -

Schistosoma mansoni is responsible for the neglected tropical disease schistosomiasis that affects 210 million people in 76 countries. Here we present analysis of the 363 megabase nuclear genome of the blood fluke. It encodes at least 11,809 genes, with an unusual intron size distribution, and new families of micro-exon genes that undergo frequent alternative splicing. As the first sequenced flatworm, and a representative of the Lophotrochozoa, it offers insights into early events in the evolution of the animals, including the development of a body pattern with bilateral symmetry, and the development of tissues into organs. Our analysis has been informed by the need to find new drug targets. The deficits in lipid metabolism that make schistosomes dependent on the host are revealed, and the identification of membrane receptors, ion channels and more than 300 proteases provide new insights into the biology of the life cycle and new targets. Bioinformatics approaches have identified metabolic chokepoints, and a chemogenomic screen has pinpointed schistosome proteins for which existing drugs may be active. The information generated provides an invaluable resource for the research community to develop much needed new control tools for the treatment and eradication of this important and neglected disease.

VL - 460 CP - 7253 M3 - 10.1038/nature08160 ER - TY - JOUR T1 - Genomic organization and expression profile of the mucin-associated surface protein (masp) family of the human pathogen Trypanosoma cruzi. JF - Nucleic Acids Res Y1 - 2009 A1 - Bartholomeu, Daniella C A1 - Cerqueira, Gustavo C A1 - Leão, Ana Carolina A A1 - daRocha, Wanderson D A1 - Pais, Fabiano S A1 - Macedo, Camila A1 - Djikeng, Appolinaire A1 - Teixeira, Santuza M R A1 - El-Sayed, Najib M KW - 3' Flanking Region KW - 5' Flanking Region KW - Amino Acid Sequence KW - Animals KW - Base Sequence KW - Conserved Sequence KW - Gene Expression Profiling KW - Genes, Protozoan KW - Genome, Protozoan KW - Membrane Proteins KW - Molecular Sequence Data KW - Mucins KW - Multigene Family KW - Protozoan Proteins KW - RNA, Messenger KW - Trypanosoma cruzi AB -

A novel large multigene family was recently identified in the human pathogen Trypanosoma cruzi, causative agent of Chagas disease, and corresponds to approximately 6% of the parasite diploid genome. The predicted gene products, mucin-associated surface proteins (MASPs), are characterized by highly conserved N- and C-terminal domains and a strikingly variable and repetitive central region. We report here an analysis of the genomic organization and expression profile of masp genes. Masps are not randomly distributed throughout the genome but instead are clustered with genes encoding mucin and other surface protein families. Masp transcripts vary in size, are preferentially expressed during the trypomastigote stage and contain highly conserved 5' and 3' untranslated regions. A sequence analysis of a trypomastigote cDNA library reveals the expression of multiple masp variants with a bias towards a particular masp subgroup. Immunofluorescence assays using antibodies generated against a MASP peptide reveals that the expression of particular MASPs at the cell membrane is limited to subsets of the parasite population. Western blots of phosphatidylinositol-specific phospholipase C (PI-PLC)-treated parasites suggest that MASP may be GPI-anchored and shed into the medium culture, thus contributing to the large repertoire of parasite polypeptides that are exposed to the host immune system.

VL - 37 CP - 10 M3 - 10.1093/nar/gkp172 ER - TY - CHAP T1 - The Genus Vibrio and Related Genera T2 - Practical handbook of microbiologyPractical handbook of microbiology Y1 - 2009 A1 - Rita R. Colwell A1 - Chun, J. ED - Goldman, Emanuel ED - Green, Lorrence H. JA - Practical handbook of microbiologyPractical handbook of microbiology PB - CRC Press SN - 9780849393655 ER - TY - Generic T1 - Inexact Local Alignment Search over Suffix Arrays T2 - IEEE International Conference on Bioinformatics and Biomedicine, 2009. BIBM '09 Y1 - 2009 A1 - Ghodsi, M. A1 - M. Pop KW - bacteria KW - Bioinformatics KW - biology computing KW - Computational Biology KW - Costs KW - DNA KW - DNA homology searches KW - DNA sequences KW - Educational institutions KW - generalized heuristic KW - genes KW - Genetics KW - genome alignment KW - Genomics KW - human KW - inexact local alignment search KW - inexact seeds KW - local alignment KW - local alignment tools KW - memory efficient suffix array KW - microorganisms KW - molecular biophysics KW - mouse KW - Organisms KW - Sensitivity and Specificity KW - sequences KW - suffix array KW - USA Councils AB - We describe an algorithm for finding approximate seeds for DNA homology searches. In contrast to previous algorithms that use exact or spaced seeds, our approximate seeds may contain insertions and deletions. We present a generalized heuristic for finding such seeds efficiently and prove that the heuristic does not affect sensitivity. We show how to adapt this algorithm to work over the memory efficient suffix array with provably minimal overhead in running time. We demonstrate the effectiveness of our algorithm on two tasks: whole genome alignment of bacteria and alignment of the DNA sequences of 177 genes that are orthologous in human and mouse. We show our algorithm achieves better sensitivity and uses less memory than other commonly used local alignment tools. JA - IEEE International Conference on Bioinformatics and Biomedicine, 2009. BIBM '09 PB - IEEE SN - 978-0-7695-3885-3 ER - TY - JOUR T1 - InterPro: the integrative protein signature database. JF - Nucleic Acids Res Y1 - 2009 A1 - Hunter, Sarah A1 - Apweiler, Rolf A1 - Attwood, Teresa K A1 - Bairoch, Amos A1 - Bateman, Alex A1 - Binns, David A1 - Bork, Peer A1 - Das, Ujjwal A1 - Daugherty, Louise A1 - Duquenne, Lauranne A1 - Finn, Robert D A1 - Gough, Julian A1 - Haft, Daniel A1 - Hulo, Nicolas A1 - Kahn, Daniel A1 - Kelly, Elizabeth A1 - Laugraud, Aurélie A1 - Letunic, Ivica A1 - Lonsdale, David A1 - Lopez, Rodrigo A1 - Madera, Martin A1 - Maslen, John A1 - McAnulla, Craig A1 - McDowall, Jennifer A1 - Mistry, Jaina A1 - Mitchell, Alex A1 - Mulder, Nicola A1 - Natale, Darren A1 - Orengo, Christine A1 - Quinn, Antony F A1 - Selengut, Jeremy D A1 - Sigrist, Christian J A A1 - Thimma, Manjula A1 - Thomas, Paul D A1 - Valentin, Franck A1 - Wilson, Derek A1 - Wu, Cathy H A1 - Yeats, Corin KW - Databases, Protein KW - Proteins KW - Sequence Analysis, Protein KW - Systems Integration AB -

The InterPro database (http://www.ebi.ac.uk/interpro/) integrates together predictive models or 'signatures' representing protein domains, families and functional sites from multiple, diverse source databases: Gene3D, PANTHER, Pfam, PIRSF, PRINTS, ProDom, PROSITE, SMART, SUPERFAMILY and TIGRFAMs. Integration is performed manually and approximately half of the total approximately 58,000 signatures available in the source databases belong to an InterPro entry. Recently, we have started to also display the remaining un-integrated signatures via our web interface. Other developments include the provision of non-signature data, such as structural data, in new XML files on our FTP site, as well as the inclusion of matchless UniProtKB proteins in the existing match XML files. The web interface has been extended and now links out to the ADAN predicted protein-protein interaction database and the SPICE and Dasty viewers. The latest public release (v18.0) covers 79.8% of UniProtKB (v14.1) and consists of 16 549 entries. InterPro data may be accessed either via the web address above, via web services, by downloading files by anonymous FTP or by using the InterProScan search software (http://www.ebi.ac.uk/Tools/InterProScan/).

VL - 37 CP - Database issue M3 - 10.1093/nar/gkn785 ER - TY - JOUR T1 - InterPro: the integrative protein signature database JF - Nucleic acids researchNucleic Acids Research Y1 - 2009 A1 - Hunter, Sarah A1 - Apweiler, Rolf A1 - Attwood, Teresa K. A1 - Bairoch, Amos A1 - Bateman, Alex A1 - Binns, David A1 - Bork, Peer A1 - Das, Ujjwal A1 - Daugherty, Louise A1 - Duquenne, Lauranne A1 - Finn, Robert D. A1 - Gough, Julian A1 - Haft, Daniel A1 - Hulo, Nicolas A1 - Kahn, Daniel A1 - Kelly, Elizabeth A1 - Laugraud, Aurélie A1 - Letunic, Ivica A1 - Lonsdale, David A1 - Lopez, Rodrigo A1 - Madera, Martin A1 - Maslen, John A1 - McAnulla, Craig A1 - McDowall, Jennifer A1 - Mistry, Jaina A1 - Mitchell, Alex A1 - Mulder, Nicola A1 - Natale, Darren A1 - Orengo, Christine A1 - Quinn, Antony F. A1 - J. Selengut A1 - Sigrist, Christian J. A. A1 - Thimma, Manjula A1 - Thomas, Paul D. A1 - Valentin, Franck A1 - Wilson, Derek A1 - Wu, Cathy H. A1 - Yeats, Corin KW - Databases, Protein KW - Proteins KW - Sequence Analysis, Protein KW - Systems Integration AB - The InterPro database (http://www.ebi.ac.uk/interpro/) integrates together predictive models or 'signatures' representing protein domains, families and functional sites from multiple, diverse source databases: Gene3D, PANTHER, Pfam, PIRSF, PRINTS, ProDom, PROSITE, SMART, SUPERFAMILY and TIGRFAMs. Integration is performed manually and approximately half of the total approximately 58,000 signatures available in the source databases belong to an InterPro entry. Recently, we have started to also display the remaining un-integrated signatures via our web interface. Other developments include the provision of non-signature data, such as structural data, in new XML files on our FTP site, as well as the inclusion of matchless UniProtKB proteins in the existing match XML files. The web interface has been extended and now links out to the ADAN predicted protein-protein interaction database and the SPICE and Dasty viewers. The latest public release (v18.0) covers 79.8% of UniProtKB (v14.1) and consists of 16 549 entries. InterPro data may be accessed either via the web address above, via web services, by downloading files by anonymous FTP or by using the InterProScan search software (http://www.ebi.ac.uk/Tools/InterProScan/). VL - 37 N1 - http://www.ncbi.nlm.nih.gov/pubmed/18940856?dopt=Abstract ER - TY - Generic T1 - Measuring differential gene expression by short read sequencing: quantitative comparison to 2-channel gene expression microarrays Y1 - 2009 A1 - Bloom, Joshua S A1 - Khan, Zia A1 - Kruglyak, Leonid A1 - Singh, Mona A1 - Caudy, Amy A JA - BMC Genomics VL - 10 UR - http://www.biomedcentral.com/1471-2164/10/221 CP - 1 J1 - BMC GenomicsBMC Genomics M3 - 10.1186/1471-2164-10-221 ER - TY - JOUR T1 - Measuring differential gene expression by short read sequencing: quantitative comparison to 2-channel gene expression microarrays. JF - BMC Genomics Y1 - 2009 A1 - Bloom, Joshua S A1 - Khan, Zia A1 - Kruglyak, Leonid A1 - Singh, Mona A1 - Caudy, Amy A KW - algorithms KW - DNA, Complementary KW - DNA, Fungal KW - Gene Expression Profiling KW - Oligonucleotide Array Sequence Analysis KW - Saccharomyces cerevisiae KW - sequence alignment KW - Sequence Analysis, DNA AB -

BACKGROUND: High-throughput cDNA synthesis and sequencing of poly(A)-enriched RNA is rapidly emerging as a technology competing to replace microarrays as a quantitative platform for measuring gene expression.

RESULTS: Consequently, we compared full length cDNA sequencing to 2-channel gene expression microarrays in the context of measuring differential gene expression. Because of its comparable cost to a gene expression microarray, our study focused on the data obtainable from a single lane of an Illumina 1 G sequencer. We compared sequencing data to a highly replicated microarray experiment profiling two divergent strains of S. cerevisiae.

CONCLUSION: Using a large number of quantitative PCR (qPCR) assays, more than previous studies, we found that neither technology is decisively better at measuring differential gene expression. Further, we report sequencing results from a diploid hybrid of two strains of S. cerevisiae that indicate full length cDNA sequencing can discover heterozygosity and measure quantitative allele-specific expression simultaneously.

VL - 10 M3 - 10.1186/1471-2164-10-221 ER - TY - JOUR T1 - Microbial oceanography in a sea of opportunity JF - NatureNature Y1 - 2009 A1 - Bowler, Chris A1 - Karl, David M. A1 - Rita R. Colwell KW - Astronomy KW - astrophysics KW - Biochemistry KW - Bioinformatics KW - Biology KW - biotechnology KW - cancer KW - cell cycle KW - cell signalling KW - climate change KW - Computational Biology KW - development KW - developmental biology KW - DNA KW - drug discovery KW - earth science KW - ecology KW - environmental science KW - Evolution KW - evolutionary biology KW - functional genomics KW - Genetics KW - Genomics KW - geophysics KW - immunology KW - interdisciplinary science KW - life KW - marine biology KW - materials science KW - medical research KW - medicine KW - metabolomics KW - molecular biology KW - molecular interactions KW - nanotechnology KW - Nature KW - neurobiology KW - neuroscience KW - palaeobiology KW - pharmacology KW - Physics KW - proteomics KW - quantum physics KW - RNA KW - Science KW - science news KW - science policy KW - signal transduction KW - structural biology KW - systems biology KW - transcriptomics AB - Plankton use solar energy to drive the nutrient cycles that make the planet habitable for larger organisms. We can now explore the diversity and functions of plankton using genomics, revealing the gene repertoires associated with survival in the oceans. Such studies will help us to appreciate the sensitivity of ocean systems and of the ocean's response to climate change, improving the predictive power of climate models. VL - 459 SN - 0028-0836 ER - TY - JOUR T1 - Mimosa: mixture model of co-expression to detect modulators of regulatory interaction JF - Algorithms in BioinformaticsAlgorithms in Bioinformatics Y1 - 2009 A1 - Hansen, M. A1 - Everett, L. A1 - Singh, L. A1 - Sridhar Hannenhalli PB - Springer Berlin/Heidelberg ER - TY - JOUR T1 - Model-based quality assessment and base-calling for second-generation sequencing data JF - Johns Hopkins University, Dept. of Biostatistics Working PapersJohns Hopkins University, Dept. of Biostatistics Working Papers Y1 - 2009 A1 - Irizarry, R. A. A1 - Héctor Corrada Bravo ER - TY - JOUR T1 - Modeling and visualization of human activities for multicamera networks JF - EURASIP Journal on Image and Video ProcessingEURASIP Journal on Image and Video Processing Y1 - 2009 A1 - Sankaranarayanan, A. C. A1 - Patro, R. A1 - Turaga, P. A1 - Varshney, Amitabh A1 - Chellappa, Rama VL - 2009 ER - TY - JOUR T1 - Motifs and cis-regulatory modules mediating the expression of genes co-expressed in presynaptic neurons JF - Genome BiologyGenome Biology Y1 - 2009 A1 - Liu, Rui A1 - Sridhar Hannenhalli A1 - Bucan, Maja AB - Hundreds of proteins modulate neurotransmitter release and synaptic plasticity during neuronal development and in response to synaptic activity. The expression of genes in the pre- and post-synaptic neurons is under stringent spatio-temporal control, but the mechanism underlying the neuronal expression of these genes remains largely unknown. VL - 10 SN - 1465-6906 ER - TY - JOUR T1 - New records of phytoplankton for Bangladesh. 9. Some rare and a new species JF - Bangladesh Journal of Plant TaxonomyBangladesh Journal of Plant Taxonomy Y1 - 2009 A1 - Khondker, Moniruzzaman A1 - Bhuiyan, Rauf Ahmed A1 - Yeasmin, Jenat A1 - Alam, Munirul A1 - Sack, R. Bradley A1 - Huq, Anwar A1 - Rita R. Colwell AB - Ten taxa belonging to Chlorophyceae, Cyanophyceae, Bacillariophyceae and Euglenophyceae, and one with an uncertain taxonomic position have been described in this paper. Of these, 10 taxa have been found to be globally rare and new records for Bangladesh, whereas Strombomonas islamii Khondker sp. nov. has been described as new to science. VL - 16 SN - 1028-2092 ER - TY - CONF T1 - Novel computational methods for large scale genome comparison T2 - 2nd International Workshop on Practical Applications of Computational Biology and Bioinformatics (IWPACBB 2008) Y1 - 2009 A1 - Todd Treangen A1 - Messeguer, Xavier JA - 2nd International Workshop on Practical Applications of Computational Biology and Bioinformatics (IWPACBB 2008) PB - Springer ER - TY - JOUR T1 - A Novel Heuristic for Local Multiple Alignment of Interspersed DNA Repeats JF - IEEE/ACM Transactions on Computational Biology and Bioinformatics Y1 - 2009 A1 - Todd Treangen A1 - Darling, A.E. A1 - Achaz, G. A1 - Ragan, M.A. A1 - Messeguer, X. A1 - Rocha, E.P.C. VL - 6 UR - http://ieeexplore.ieee.org/document/4770094/http://xplorestaging.ieee.org/ielx5/8857/4907697/04770094.pdf?arnumber=4770094 CP - 2 J1 - IEEE/ACM Trans. Comput. Biol. and Bioinf. M3 - 10.1109/TCBB.2009.9 ER - TY - JOUR T1 - A novel heuristic for local multiple alignment of interspersed DNA repeats JF - IEEE/ACM Transactions on Computational Biology and Bioinformatics (TCBB) Y1 - 2009 A1 - Todd Treangen A1 - Darling, Aaron E A1 - Achaz, Guillaume A1 - Ragan, Mark A A1 - Messeguer, Xavier A1 - Rocha, Eduardo PC VL - 6 ER - TY - JOUR T1 - Parametric Complexity of Sequence Assembly: Theory and Applications to Next Generation Sequencing JF - Journal of Computational BiologyJournal of Computational Biology Y1 - 2009 A1 - Nagarajan, Niranjan A1 - M. Pop AB - In recent years, a flurry of new DNA sequencing technologies have altered the landscape of genomics, providing a vast amount of sequence information at a fraction of the costs that were previously feasible. The task of assembling these sequences into a genome has, however, still remained an algorithmic challenge that is in practice answered by heuristic solutions. In order to design better assembly algorithms and exploit the characteristics of sequence data from new technologies, we need an improved understanding of the parametric complexity of the assembly problem. In this article, we provide a first theoretical study in this direction, exploring the connections between repeat complexity, read lengths, overlap lengths and coverage in determining the “hard” instances of the assembly problem. Our work suggests at least two ways in which existing assemblers can be extended in a rigorous fashion, in addition to delineating directions for future theoretical investigations. VL - 16 SN - 1066-5277, 1557-8666 ER - TY - JOUR T1 - A phylogenetic mixture model for the evolution of gene expression JF - Molecular biology and evolutionMolecular biology and evolution Y1 - 2009 A1 - Eng, K. H. A1 - Héctor Corrada Bravo A1 - Keles, S. VL - 26 ER - TY - Generic T1 - A practical algorithm for finding maximal exact matches in large sequence datasets using sparse suffix arrays Y1 - 2009 A1 - Khan, Z. A1 - Bloom, J. S. A1 - Kruglyak, L. A1 - Singh, M. JA - Bioinformatics VL - 25 UR - http://bioinformatics.oxfordjournals.org/cgi/doi/10.1093/bioinformatics/btp275 CP - 13 J1 - Bioinformatics M3 - 10.1093/bioinformatics/btp275 ER - TY - JOUR T1 - A practical algorithm for finding maximal exact matches in large sequence datasets using sparse suffix arrays. JF - Bioinformatics Y1 - 2009 A1 - Khan, Zia A1 - Bloom, Joshua S A1 - Kruglyak, Leonid A1 - Singh, Mona KW - algorithms KW - Base Sequence KW - Genomics KW - sequence alignment KW - Sequence Analysis, DNA AB -

MOTIVATION: High-throughput sequencing technologies place ever increasing demands on existing algorithms for sequence analysis. Algorithms for computing maximal exact matches (MEMs) between sequences appear in two contexts where high-throughput sequencing will vastly increase the volume of sequence data: (i) seeding alignments of high-throughput reads for genome assembly and (ii) designating anchor points for genome-genome comparisons.

RESULTS: We introduce a new algorithm for finding MEMs. The algorithm leverages a sparse suffix array (SA), a text index that stores every K-th position of the text. In contrast to a full text index that stores every position of the text, a sparse SA occupies much less memory. Even though we use a sparse index, the output of our algorithm is the same as a full text index algorithm as long as the space between the indexed suffixes is not greater than a minimum length of a MEM. By relying on partial matches and additional text scanning between indexed positions, the algorithm trades memory for extra computation. The reduced memory usage makes it possible to determine MEMs between significantly longer sequences.

AVAILABILITY: Source code for the algorithm is available under a BSD open source license at http://compbio.cs.princeton.edu/mems. The implementation can serve as a drop-in replacement for the MEMs algorithm in MUMmer 3.

VL - 25 CP - 13 M3 - 10.1093/bioinformatics/btp275 ER - TY - JOUR T1 - Predicting the distribution of Vibrio spp. in the Chesapeake Bay: a Vibrio cholerae case study JF - EcoHealthEcoHealth Y1 - 2009 A1 - Constantin de Magny, G. A1 - Long, W. A1 - Brown, C. W. A1 - Hood, R. R. A1 - Huq, A. A1 - Murtugudde, R. A1 - Rita R. Colwell AB - Vibrio cholerae, the causative agent of cholera, is a naturally occurring inhabitant of the Chesapeake Bay and serves as a predictor for other clinically important vibrios, including Vibrio parahaemolyticus and Vibrio vulnificus. A system was constructed to predict the likelihood of the presence of V. cholerae in surface waters of the Chesapeake Bay, with the goal to provide forecasts of the occurrence of this and related pathogenic Vibrio spp. Prediction was achieved by driving an available multivariate empirical habitat model estimating the probability of V. cholerae within a range of temperatures and salinities in the Bay, with hydrodynamically generated predictions of ambient temperature and salinity. The experimental predictions provided both an improved understanding of the in situ variability of V. cholerae, including identification of potential hotspots of occurrence, and usefulness as an early warning system. With further development of the system, prediction of the probability of the occurrence of related pathogenic vibrios in the Chesapeake Bay, notably V. parahaemolyticus and V. vulnificus, will be possible, as well as its transport to any geographical location where sufficient relevant data are available. VL - 6 ER - TY - Generic T1 - Protein quantification across hundreds of experimental conditions Y1 - 2009 A1 - Khan, Z. A1 - Bloom, J. S. A1 - Garcia, B. A. A1 - Singh, M. A1 - Kruglyak, L. JA - Proceedings of the National Academy of Sciences VL - 106 UR - http://www.pnas.org/cgi/doi/10.1073/pnas.0904100106 CP - 37 J1 - Proceedings of the National Academy of Sciences M3 - 10.1073/pnas.0904100106 ER - TY - JOUR T1 - Protein quantification across hundreds of experimental conditions. JF - Proc Natl Acad Sci U S A Y1 - 2009 A1 - Khan, Zia A1 - Bloom, Joshua S A1 - Garcia, Benjamin A A1 - Singh, Mona A1 - Kruglyak, Leonid KW - algorithms KW - Animals KW - Automatic Data Processing KW - Chromatography, Liquid KW - Databases, Factual KW - Fungal Proteins KW - HUMANS KW - Isotopes KW - Mice KW - Proteins KW - proteomics KW - Tandem Mass Spectrometry AB -

Quantitative studies of protein abundance rarely span more than a small number of experimental conditions and replicates. In contrast, quantitative studies of transcript abundance often span hundreds of experimental conditions and replicates. This situation exists, in part, because extracting quantitative data from large proteomics datasets is significantly more difficult than reading quantitative data from a gene expression microarray. To address this problem, we introduce two algorithmic advances in the processing of quantitative proteomics data. First, we use space-partitioning data structures to handle the large size of these datasets. Second, we introduce techniques that combine graph-theoretic algorithms with space-partitioning data structures to collect relative protein abundance data across hundreds of experimental conditions and replicates. We validate these algorithmic techniques by analyzing several datasets and computing both internal and external measures of quantification accuracy. We demonstrate the scalability of these techniques by applying them to a large dataset that comprises a total of 472 experimental conditions and replicates.

VL - 106 CP - 37 M3 - 10.1073/pnas.0904100106 ER - TY - JOUR T1 - PTM-Switchboard—a database of posttranslational modifications of transcription factors, the mediating enzymes and target genes JF - Nucleic acids researchNucleic Acids Research Y1 - 2009 A1 - Everett, L. A1 - Vo, A. A1 - Sridhar Hannenhalli PB - Oxford Univ Press VL - 37 ER - TY - JOUR T1 - Resistin gene variation is associated with systemic inflammation but not plasma adipokine levels, metabolic syndrome or coronary atherosclerosis in nondiabetic Caucasians JF - Clinical EndocrinologyClinical Endocrinology Y1 - 2009 A1 - Qasim, Atif N. A1 - Metkus, Thomas S. A1 - Tadesse, Mahlet A1 - Lehrke, Michael A1 - Restine, Stephanie A1 - Wolfe, Megan L. A1 - Sridhar Hannenhalli A1 - Cappola, Thomas A1 - Rader, Daniel J. A1 - Reilly, Muredach P. AB - Objective Resistin causes insulin resistance and diabetes in mice whereas in humans it is linked to inflammation and atherosclerosis. Few human genetic studies of resistin in inflammation and atherosclerosis have been performed. We hypothesized that the –420C>G putative gain-of-function resistin variant would be associated with inflammatory markers and atherosclerosis but not with metabolic syndrome or adipokines in humans.Design and methods We examined the association of three resistin polymorphisms, –852A>G, –420C>G and +157C>T, and related haplotypes with plasma resistin, cytokines, C-reactive protein (CRP), adipokines, plasma lipoproteins, metabolic syndrome and coronary artery calcification (CAC) in nondiabetic Caucasians (n = 851). Results Resistin levels were higher, dose-dependently, with the –420G allele (CC 5·9 ± 2·7 ng/ml, GC 6·5 ± 4·0 ng/ml and GG 7·2 ± 4·8 ng/ml, trend P = 0·04) after age and gender adjustment [fold higher for GC + GG vs. CC; 1·07 (1·00–1·15), P < 0·05)]. The –852A>G single nucleotide polymorphism (SNP) was associated with higher soluble tumour necrosis factor-receptor 2 (sol-TNFR2) levels in fully adjusted models [1·06 (95% CI 1·01–1·11), P = 0·01)]. The estimated resistin haplotype (GGT) was associated with sol-TNFR2 (P = 0·04) and the AGT haplotype was related to CRP (P = 0·04) in the fully adjusted models. Resistin SNPs and haplotypes were not associated with body mass index (BMI), fasting glucose, insulin resistance, metabolic syndrome, adipokines or CAC scores. Conclusions Despite modest associations with plasma resistin and inflammatory biomarkers, resistin 5′ variants were not associated with metabolic parameters or coronary calcification. This suggests that resistin is an inflammatory cytokine in humans but has little influence on adiposity, metabolic syndrome or atherosclerosis. VL - 70 SN - 1365-2265 ER - TY - JOUR T1 - Revealing biological modules via graph summarization JF - Journal of Computational BiologyJournal of Computational Biology Y1 - 2009 A1 - Navlakha, S. A1 - Schatz, M. C. A1 - Kingsford, Carl VL - 16 ER - TY - JOUR T1 - RNA Colony Blot Hybridization Method for Enumeration of Culturable Vibrio Cholerae and Vibrio Mimicus Bacteria JF - Applied and Environmental MicrobiologyAppl. Environ. Microbiol.Applied and Environmental MicrobiologyAppl. Environ. Microbiol. Y1 - 2009 A1 - Grim, Christopher J. A1 - Zo, Young-Gun A1 - Hasan, Nur A. A1 - Ali, Afsar A1 - Chowdhury, Wasimul B. A1 - Islam, Atiqul A1 - Rashid, Mohammed H. A1 - Alam, Munirul A1 - Morris, J. Glenn A1 - Huq, Anwar A1 - Rita R. Colwell AB - A species-specific RNA colony blot hybridization protocol was developed for enumeration of culturable Vibrio cholerae and Vibrio mimicus bacteria in environmental water samples. Bacterial colonies on selective or nonselective plates were lysed by sodium dodecyl sulfate, and the lysates were immobilized on nylon membranes. A fluorescently labeled oligonucleotide probe targeting a phylogenetic signature sequence of 16S rRNA of V. cholerae and V. mimicus was hybridized to rRNA molecules immobilized on the nylon colony lift blots. The protocol produced strong positive signals for all colonies of the 15 diverse V. cholerae-V. mimicus strains tested, indicating 100% sensitivity of the probe for the targeted species. For visible colonies of 10 nontarget species, the specificity of the probe was calculated to be 90% because of a weak positive signal produced by Grimontia (Vibrio) hollisae, a marine bacterium. When both the sensitivity and specificity of the assay were evaluated using lake water samples amended with a bioluminescent V. cholerae strain, no false-negative or false-positive results were found, indicating 100% sensitivity and specificity for culturable bacterial populations in freshwater samples when G. hollisae was not present. When the protocol was applied to laboratory microcosms containing V. cholerae attached to live copepods, copepods were found to carry approximately 10,000 to 50,000 CFU of V. cholerae per copepod. The protocol was also used to analyze pond water samples collected in an area of cholera endemicity in Bangladesh over a 9-month period. Water samples collected from six ponds demonstrated a peak in abundance of total culturable V. cholerae bacteria 1 to 2 months prior to observed increases in pathogenic V. cholerae and in clinical cases recorded by the area health clinic. The method provides a highly specific and sensitive tool for monitoring the dynamics of V. cholerae in the environment. The RNA blot hybridization protocol can also be applied to detection of other gram-negative bacteria for taxon-specific enumeration. VL - 75 SN - 0099-2240, 1098-5336 ER - TY - CHAP T1 - Salient Frame Detection for Molecular Dynamics Simulations T2 - Scientific VisualizationScientific Visualization Y1 - 2009 A1 - Kim, Youngmin A1 - Patro, Robert A1 - Ip, Cheuk Yiu A1 - O'Leary, Dianne P. A1 - Anishkin, Andriy A1 - Sukharev, Sergei A1 - Varshney, Amitabh ED - Ebert, D. S. ED - Gr, ED - x6f, ED - x, ED - ller, E. ED - Hagen, H. ED - Kaufman, A. JA - Scientific VisualizationScientific Visualization PB - Dagstuhl Seminar Proceedings 09251 ER - TY - JOUR T1 - Searching for SNPs with cloud computing JF - Genome BiologyGenome Biology Y1 - 2009 A1 - Langmead, Ben A1 - Schatz, Michael C. A1 - Jimmy, Lin A1 - M. Pop A1 - Salzberg, Steven L. AB - As DNA sequencing outpaces improvements in computer speed, there is a critical need to accelerate tasks like alignment and SNP calling. Crossbow is a cloud-computing software tool that combines the aligner Bowtie and the SNP caller SOAPsnp. Executing in parallel using Hadoop, Crossbow analyzes data comprising 38-fold coverage of the human genome in three hours using a 320-CPU cluster rented from a cloud computing service for about $85. Crossbow is available from http://bowtie-bio.sourceforge.net/crossbow/. VL - 10 SN - 1465-6906 ER - TY - JOUR T1 - Serogroup, Virulence, and Genetic Traits of Vibrio Parahaemolyticus in the Estuarine Ecosystem of Bangladesh JF - Applied and Environmental MicrobiologyAppl. Environ. Microbiol.Applied and Environmental MicrobiologyAppl. Environ. Microbiol. Y1 - 2009 A1 - Alam, Munirul A1 - Chowdhury, Wasimul B. A1 - Bhuiyan, N. A. A1 - Islam, Atiqul A1 - Hasan, Nur A. A1 - Nair, G. Balakrish A1 - Watanabe, H. A1 - Siddique, A. K. A1 - Huq, Anwar A1 - Sack, R. Bradley A1 - Akhter, M. Z. A1 - Grim, Christopher J. A1 - Kam, K. M. A1 - Luey, C. K. Y. A1 - Endtz, Hubert P. A1 - Cravioto, Alejandro A1 - Rita R. Colwell AB - Forty-two strains of Vibrio parahaemolyticus were isolated from Bay of Bengal estuaries and, with two clinical strains, analyzed for virulence, phenotypic, and molecular traits. Serological analysis indicated O8, O3, O1, and K21 to be the major O and K serogroups, respectively, and O8:K21, O1:KUT, and O3:KUT to be predominant. The K antigen(s) was untypeable, and pandemic serogroup O3:K6 was not detected. The presence of genes toxR and tlh were confirmed by PCR in all but two strains, which also lacked toxR. A total of 18 (41%) strains possessed the virulence gene encoding thermostable direct hemolysin (TDH), and one had the TDH-related hemolysin (trh) gene, but not tdh. Ten (23%) strains exhibited Kanagawa phenomenon that surrogates virulence, of which six, including the two clinical strains, possessed tdh. Of the 18 tdh-positive strains, 17 (94%), including the two clinical strains, had the seromarker O8:K21, one was O9:KUT, and the single trh-positive strain was O1:KUT. None had the group-specific or ORF8 pandemic marker gene. DNA fingerprinting employing pulsed-field gel electrophoresis (PFGE) of SfiI-digested DNA and cluster analysis showed divergence among the strains. Dendrograms constructed using PFGE (SfiI) images from a soft database, including those of pandemic and nonpandemic strains of diverse geographic origin, however, showed that local strains formed a cluster, i.e., “clonal cluster,” as did pandemic strains of diverse origin. The demonstrated prevalence of tdh-positive and diarrheagenic serogroup O8:K21 strains in coastal villages of Bangladesh indicates a significant human health risk for inhabitants. VL - 75 SN - 0099-2240, 1098-5336 ER - TY - JOUR T1 - Statistical Methods for Detecting Differentially Abundant Features in Clinical Metagenomic Samples JF - PLoS Comput BiologyPLoS Comput BiolPLoS Comput BiologyPLoS Comput Biol Y1 - 2009 A1 - White, James Robert A1 - Nagarajan, Niranjan A1 - M. Pop AB - The emerging field of metagenomics aims to understand the structure and function of microbial communities solely through DNA analysis. Current metagenomics studies comparing communities resemble large-scale clinical trials with multiple subjects from two general populations (e.g. sick and healthy). To improve analyses of this type of experimental data, we developed a statistical methodology for detecting differentially abundant features between microbial communities, that is, features that are enriched or depleted in one population versus another. We show our methods are applicable to various metagenomic data ranging from taxonomic information to functional annotations. We also provide an assessment of taxonomic differences in gut microbiota between lean and obese humans, as well as differences between the functional capacities of mature and infant gut microbiomes, and those of microbial and viral metagenomes. Our methods are the first to statistically address differential abundance in comparative metagenomics studies with multiple subjects, and we hope will give researchers a more complete picture of how exactly two environments differ. VL - 5 ER - TY - JOUR T1 - A synthesis for exactly 3-edge-connected graphs JF - Arxiv preprint arXiv:0905.1053Arxiv preprint arXiv:0905.1053 Y1 - 2009 A1 - Kingsford, Carl A1 - Marçais, G. ER - TY - JOUR T1 - Three genomes from the phylum Acidobacteria provide insight into the lifestyles of these microorganisms in soils JF - Applied and environmental microbiologyApplied and environmental microbiology Y1 - 2009 A1 - Ward, Naomi L. A1 - Challacombe, Jean F. A1 - Janssen, Peter H. A1 - Henrissat, Bernard A1 - Coutinho, Pedro M. A1 - Wu, Martin A1 - Xie, Gary A1 - Haft, Daniel H. A1 - Sait, Michelle A1 - Badger, Jonathan A1 - Barabote, Ravi D. A1 - Bradley, Brent A1 - Brettin, Thomas S. A1 - Brinkac, Lauren M. A1 - Bruce, David A1 - Creasy, Todd A1 - Daugherty, Sean C. A1 - Davidsen, Tanja M. A1 - DeBoy, Robert T. A1 - Detter, J. Chris A1 - Dodson, Robert J. A1 - Durkin, A. Scott A1 - Ganapathy, Anuradha A1 - Gwinn-Giglio, Michelle A1 - Han, Cliff S. A1 - Khouri, Hoda A1 - Kiss, Hajnalka A1 - Kothari, Sagar P. A1 - Madupu, Ramana A1 - Nelson, Karen E. A1 - Nelson, William C. A1 - Paulsen, Ian A1 - Penn, Kevin A1 - Ren, Qinghu A1 - Rosovitz, M. J. A1 - J. Selengut A1 - Shrivastava, Susmita A1 - Sullivan, Steven A. A1 - Tapia, Roxanne A1 - Thompson, L. Sue A1 - Watkins, Kisha L. A1 - Yang, Qi A1 - Yu, Chunhui A1 - Zafar, Nikhat A1 - Zhou, Liwei A1 - Kuske, Cheryl R. KW - Anti-Bacterial Agents KW - bacteria KW - Biological Transport KW - Carbohydrate Metabolism KW - Cyanobacteria KW - DNA, Bacterial KW - Fungi KW - Genome, Bacterial KW - Macrolides KW - Molecular Sequence Data KW - Nitrogen KW - Phylogeny KW - Proteobacteria KW - Sequence Analysis, DNA KW - Sequence Homology KW - Soil Microbiology AB - The complete genomes of three strains from the phylum Acidobacteria were compared. Phylogenetic analysis placed them as a unique phylum. They share genomic traits with members of the Proteobacteria, the Cyanobacteria, and the Fungi. The three strains appear to be versatile heterotrophs. Genomic and culture traits indicate the use of carbon sources that span simple sugars to more complex substrates such as hemicellulose, cellulose, and chitin. The genomes encode low-specificity major facilitator superfamily transporters and high-affinity ABC transporters for sugars, suggesting that they are best suited to low-nutrient conditions. They appear capable of nitrate and nitrite reduction but not N(2) fixation or denitrification. The genomes contained numerous genes that encode siderophore receptors, but no evidence of siderophore production was found, suggesting that they may obtain iron via interaction with other microorganisms. The presence of cellulose synthesis genes and a large class of novel high-molecular-weight excreted proteins suggests potential traits for desiccation resistance, biofilm formation, and/or contribution to soil structure. Polyketide synthase and macrolide glycosylation genes suggest the production of novel antimicrobial compounds. Genes that encode a variety of novel proteins were also identified. The abundance of acidobacteria in soils worldwide and the breadth of potential carbon use by the sequenced strains suggest significant and previously unrecognized contributions to the terrestrial carbon cycle. Combining our genomic evidence with available culture traits, we postulate that cells of these isolates are long-lived, divide slowly, exhibit slow metabolic rates under low-nutrient conditions, and are well equipped to tolerate fluctuations in soil hydration. VL - 75 N1 - http://www.ncbi.nlm.nih.gov/pubmed/19201974?dopt=Abstract ER - TY - JOUR T1 - Three genomes from the phylum Acidobacteria provide insight into the lifestyles of these microorganisms in soils. JF - Appl Environ Microbiol Y1 - 2009 A1 - Ward, Naomi L A1 - Challacombe, Jean F A1 - Janssen, Peter H A1 - Henrissat, Bernard A1 - Coutinho, Pedro M A1 - Wu, Martin A1 - Xie, Gary A1 - Haft, Daniel H A1 - Sait, Michelle A1 - Badger, Jonathan A1 - Barabote, Ravi D A1 - Bradley, Brent A1 - Brettin, Thomas S A1 - Brinkac, Lauren M A1 - Bruce, David A1 - Creasy, Todd A1 - Daugherty, Sean C A1 - Davidsen, Tanja M A1 - DeBoy, Robert T A1 - Detter, J Chris A1 - Dodson, Robert J A1 - Durkin, A Scott A1 - Ganapathy, Anuradha A1 - Gwinn-Giglio, Michelle A1 - Han, Cliff S A1 - Khouri, Hoda A1 - Kiss, Hajnalka A1 - Kothari, Sagar P A1 - Madupu, Ramana A1 - Nelson, Karen E A1 - Nelson, William C A1 - Paulsen, Ian A1 - Penn, Kevin A1 - Ren, Qinghu A1 - Rosovitz, M J A1 - Selengut, Jeremy D A1 - Shrivastava, Susmita A1 - Sullivan, Steven A A1 - Tapia, Roxanne A1 - Thompson, L Sue A1 - Watkins, Kisha L A1 - Yang, Qi A1 - Yu, Chunhui A1 - Zafar, Nikhat A1 - Zhou, Liwei A1 - Kuske, Cheryl R KW - Anti-Bacterial Agents KW - bacteria KW - Biological Transport KW - Carbohydrate Metabolism KW - Cyanobacteria KW - DNA, Bacterial KW - Fungi KW - Genome, Bacterial KW - Macrolides KW - Molecular Sequence Data KW - Nitrogen KW - Phylogeny KW - Proteobacteria KW - Sequence Analysis, DNA KW - Sequence Homology KW - Soil Microbiology AB -

The complete genomes of three strains from the phylum Acidobacteria were compared. Phylogenetic analysis placed them as a unique phylum. They share genomic traits with members of the Proteobacteria, the Cyanobacteria, and the Fungi. The three strains appear to be versatile heterotrophs. Genomic and culture traits indicate the use of carbon sources that span simple sugars to more complex substrates such as hemicellulose, cellulose, and chitin. The genomes encode low-specificity major facilitator superfamily transporters and high-affinity ABC transporters for sugars, suggesting that they are best suited to low-nutrient conditions. They appear capable of nitrate and nitrite reduction but not N(2) fixation or denitrification. The genomes contained numerous genes that encode siderophore receptors, but no evidence of siderophore production was found, suggesting that they may obtain iron via interaction with other microorganisms. The presence of cellulose synthesis genes and a large class of novel high-molecular-weight excreted proteins suggests potential traits for desiccation resistance, biofilm formation, and/or contribution to soil structure. Polyketide synthase and macrolide glycosylation genes suggest the production of novel antimicrobial compounds. Genes that encode a variety of novel proteins were also identified. The abundance of acidobacteria in soils worldwide and the breadth of potential carbon use by the sequenced strains suggest significant and previously unrecognized contributions to the terrestrial carbon cycle. Combining our genomic evidence with available culture traits, we postulate that cells of these isolates are long-lived, divide slowly, exhibit slow metabolic rates under low-nutrient conditions, and are well equipped to tolerate fluctuations in soil hydration.

VL - 75 CP - 7 M3 - 10.1128/AEM.02294-08 ER - TY - JOUR T1 - Toward reconstructing the evolution of advanced moths and butterflies (Lepidoptera: Ditrysia): an initial molecular study JF - BMC Evol BiolBMC Evol Biol Y1 - 2009 A1 - Regier, J. C. A1 - Zwick, A. A1 - Michael P. Cummings A1 - Kawahara, A. Y. A1 - Cho, S. A1 - Weller, S. A1 - Roe, A. A1 - Baixeras, J. A1 - Brown, J. W. A1 - Parr, C. A1 - Davis, D. R. A1 - Epstein, M. A1 - Hallwachs, W. A1 - Hausmann, A. A1 - Janzen, D. H. A1 - Kitching, I. J. A1 - Solis, M. A. A1 - Yen, S. H. A1 - Adam L. Bazinet A1 - Mitter, C. AB - BACKGROUND: In the mega-diverse insect order Lepidoptera (butterflies and moths; 165,000 described species), deeper relationships are little understood within the clade Ditrysia, to which 98% of the species belong. To begin addressing this problem, we tested the ability of five protein-coding nuclear genes (6.7 kb total), and character subsets therein, to resolve relationships among 123 species representing 27 (of 33) superfamilies and 55 (of 100) families of Ditrysia under maximum likelihood analysis. RESULTS: Our trees show broad concordance with previous morphological hypotheses of ditrysian phylogeny, although most relationships among superfamilies are weakly supported. There are also notable surprises, such as a consistently closer relationship of Pyraloidea than of butterflies to most Macrolepidoptera. Monophyly is significantly rejected by one or more character sets for the putative clades Macrolepidoptera as currently defined (P < 0.05) and Macrolepidoptera excluding Noctuoidea and Bombycoidea sensu lato (P < or = 0.005), and nearly so for the superfamily Drepanoidea as currently defined (P < 0.08). Superfamilies are typically recovered or nearly so, but usually without strong support. Relationships within superfamilies and families, however, are often robustly resolved. We provide some of the first strong molecular evidence on deeper splits within Pyraloidea, Tortricoidea, Geometroidea, Noctuoidea and others.Separate analyses of mostly synonymous versus non-synonymous character sets revealed notable differences (though not strong conflict), including a marked influence of compositional heterogeneity on apparent signal in the third codon position (nt3). As available model partitioning methods cannot correct for this variation, we assessed overall phylogeny resolution through separate examination of trees from each character set. Exploration of "tree space" with GARLI, using grid computing, showed that hundreds of searches are typically needed to find the best-feasible phylogeny estimate for these data. CONCLUSION: Our results (a) corroborate the broad outlines of the current working phylogenetic hypothesis for Ditrysia, (b) demonstrate that some prominent features of that hypothesis, including the position of the butterflies, need revision, and (c) resolve the majority of family and subfamily relationships within superfamilies as thus far sampled. Much further gene and taxon sampling will be needed, however, to strongly resolve individual deeper nodes. VL - 9 ER - TY - JOUR T1 - Two alternatively spliced isoforms of the Arabidopsis SR45 protein have distinct roles during normal plant development. JF - Plant Physiol Y1 - 2009 A1 - Zhang, Xiao-Ning A1 - Mount, Stephen M KW - Alternative Splicing KW - Amino Acid Sequence KW - Arabidopsis KW - Arabidopsis Proteins KW - Carrier Proteins KW - Flowers KW - Molecular Sequence Data KW - Mutation KW - Plant Roots KW - Protein Isoforms KW - Ribonucleoproteins KW - RNA-Binding Proteins KW - sequence alignment AB -

The serine-arginine-rich (SR) proteins constitute a conserved family of pre-mRNA splicing factors. In Arabidopsis (Arabidopsis thaliana), they are encoded by 19 genes, most of which are themselves alternatively spliced. In the case of SR45, the use of alternative 3' splice sites 21 nucleotides apart generates two alternatively spliced isoforms. Isoform 1 (SR45.1) has an insertion relative to isoform 2 (SR45.2) that replaces a single arginine with eight amino acids (TSPQRKTG). The biological implications of SR45 alternative splicing have been unclear. A previously described loss-of-function mutant affecting both isoforms, sr45-1, shows several developmental defects, including defects in petal development and root growth. We found that the SR45 promoter is highly active in regions with actively growing and dividing cells. We also tested the ability of each SR45 isoform to complement the sr45-1 mutant by overexpression of isoform-specific green fluorescent protein (GFP) fusion proteins. As expected, transgenic plants overexpressing either isoform displayed both nuclear speckles and GFP fluorescence throughout the nucleoplasm. We found that SR45.1-GFP complements the flower petal phenotype, but not the root growth phenotype. Conversely, SR45.2-GFP complements root growth but not floral morphology. Mutation of a predicted phosphorylation site within the alternatively spliced segment, SR45.1-S219A-GFP, does not affect complementation. However, a double mutation affecting both serine-219 and the adjacent threonine-218 (SR45.1-T218A + S219A-GFP) behaves like isoform 2, complementing the root but not the floral phenotype. In conclusion, our study provides evidence that the two alternatively spliced isoforms of SR45 have distinct biological functions.

VL - 150 CP - 3 M3 - 10.1104/pp.109.138180 ER - TY - JOUR T1 - Ultrafast and memory-efficient alignment of short DNA sequences to the human genome JF - Genome BiologyGenome Biology Y1 - 2009 A1 - Langmead, Ben A1 - Trapnell, Cole A1 - M. Pop A1 - Salzberg, Steven L. AB - Bowtie is an ultrafast, memory-efficient alignment program for aligning short DNA sequence reads to large genomes. For the human genome, Burrows-Wheeler indexing allows Bowtie to align more than 25 million reads per CPU hour with a memory footprint of approximately 1.3 gigabytes. Bowtie extends previous Burrows-Wheeler techniques with a novel quality-aware backtracking algorithm that permits mismatches. Multiple processor cores can be used simultaneously to achieve even greater alignment speeds. Bowtie is open source http://bowtie.cbcb.umd.edu. VL - 10 SN - 1465-6906 ER - TY - JOUR T1 - Using Satellite Images of Environmental Changes to Predict Infectious Disease Outbreaks JF - Emerging Infectious DiseasesEmerg Infect DisEmerging Infectious DiseasesEmerg Infect Dis Y1 - 2009 A1 - Ford, Timothy E. A1 - Rita R. Colwell A1 - Rose, Joan B. A1 - Morse, Stephen S. A1 - Rogers, David J. A1 - Yates, Terry L. AB - A strong global satellite imaging system is essential for predicting outbreaks., Recent events clearly illustrate a continued vulnerability of large populations to infectious diseases, which is related to our changing human-constructed and natural environments. A single person with multidrug-resistant tuberculosis in 2007 provided a wake-up call to the United States and global public health infrastructure, as the health professionals and the public realized that today’s ease of airline travel can potentially expose hundreds of persons to an untreatable disease associated with an infectious agent. Ease of travel, population increase, population displacement, pollution, agricultural activity, changing socioeconomic structures, and international conflicts worldwide have each contributed to infectious disease events. Today, however, nothing is larger in scale, has more potential for long-term effects, and is more uncertain than the effects of climate change on infectious disease outbreaks, epidemics, and pandemics. We discuss advances in our ability to predict these events and, in particular, the critical role that satellite imaging could play in mounting an effective response. VL - 15 SN - 1080-6040 ER - TY - JOUR T1 - Viable but not cultivable bacteria JF - Uncultivated MicroorganismsUncultivated Microorganisms Y1 - 2009 A1 - Rita R. Colwell AB - A well-studied, long-term survival mechanism employed by Gram-positive bacteria is formation of endospores. For Gram-negative bacteria, the assumption has been that a survival state does not exist. However, a dormancy state has been described for Gram-negative bacteria and designated as the viable but nonculturable (VBNC) strategy of nonspore-forming cells. A variety of environmental factors are involved in induction of the viable but nonculturable state and Vibrio cholerae provides a useful paradigm for the VBNC phenomenon. It is now accepted that plate counts cannot be relied upon to enumerate or detect VBNC cells. Therefore, direct methods employing fluorescent staining, molecular genetic probes, and other molecular methods have proven both useful and reliable in detecting and enumerating both culturable and nonculturable cells. A predictive model for cholera has been developed, based on ground truth data gathered using these molecular methods and combining them with data obtained by remote sensing, employing satellites. It is clear that microbiology in the twenty-first century has been enhanced by these new tools and paradigms. ER - TY - JOUR T1 - Biofilms in water, its role and impact in human disease transmission JF - Current Opinion in BiotechnologyCurrent Opinion in Biotechnology Y1 - 2008 A1 - Huq, Anwar A1 - Whitehouse, Chris A. A1 - Grim, Christopher J. A1 - Alam, Munirul A1 - Rita R. Colwell AB - Understanding the mechanism of biofilm formation is the first step in determining its function and, thereby, its impact and role in the environment. Extensive studies accomplished during the past few years have elucidated the genetics and biochemistry of biofilm formation. Cell-to-cell communication, that is, quorum sensing, is a key factor in the initiation of biofilm. Occurrence of viable but nonculturable bacteria, including Vibrio cholerae in biofilms has been reported and most likely such cells were overlooked previously because appropriate methods of detection were not employed. For this reason discovery and investigation of this important bacterial ecological niche in the environment were impeded. VL - 19 SN - 0958-1669 ER - TY - JOUR T1 - Bioinformatics challenges of new sequencing technology JF - Trends in GeneticsTrends in Genetics Y1 - 2008 A1 - M. Pop A1 - Salzberg, Steven L. AB - New DNA sequencing technologies can sequence up to one billion bases in a single day at low cost, putting large-scale sequencing within the reach of many scientists. Many researchers are forging ahead with projects to sequence a range of species using the new technologies. However, these new technologies produce read lengths as short as 35–40 nucleotides, posing challenges for genome assembly and annotation. Here we review the challenges and describe some of the bioinformatics systems that are being proposed to solve them. We specifically address issues arising from using these technologies in assembly projects, both de novo and for resequencing purposes, as well as efforts to improve genome annotation in the fragmented assemblies produced by short read lengths. VL - 24 SN - 0168-9525 ER - TY - JOUR T1 - BIOINFORMATICS REVIEW JF - BIOINFORMATICSBioinformatics Y1 - 2008 A1 - Sridhar Hannenhalli VL - 24 ER - TY - JOUR T1 - The Complete Genome Sequence of Thermococcus Onnurineus NA1 Reveals a Mixed Heterotrophic and Carboxydotrophic Metabolism JF - Journal of BacteriologyJ. Bacteriol.Journal of BacteriologyJ. Bacteriol. Y1 - 2008 A1 - Lee, Hyun Sook A1 - Kang, Sung Gyun A1 - Bae, Seung Seob A1 - Lim, Jae Kyu A1 - Cho, Yona A1 - Kim, Yun Jae A1 - Jeon, Jeong Ho A1 - Cha, Sun-Shin A1 - Kwon, Kae Kyoung A1 - Kim, Hyung-Tae A1 - Park, Cheol-Joo A1 - Lee, Hee-Wook A1 - Kim, Seung Il A1 - Jongsik, Chun A1 - Rita R. Colwell A1 - Kim, Sang-Jin A1 - Lee, Jung-Hyun AB - Members of the genus Thermococcus, sulfur-reducing hyperthermophilic archaea, are ubiquitously present in various deep-sea hydrothermal vent systems and are considered to play a significant role in the microbial consortia. We present the complete genome sequence and feature analysis of Thermococcus onnurineus NA1 isolated from a deep-sea hydrothermal vent area, which reveal clues to its physiology. Based on results of genomic analysis, T. onnurineus NA1 possesses the metabolic pathways for organotrophic growth on peptides, amino acids, or sugars. More interesting was the discovery that the genome encoded unique proteins that are involved in carboxydotrophy to generate energy by oxidation of CO to CO2, thereby providing a mechanistic basis for growth with CO as a substrate. This lithotrophic feature in combination with carbon fixation via RuBisCO (ribulose 1,5-bisphosphate carboxylase/oxygenase) introduces a new strategy with a complementing energy supply for T. onnurineus NA1 potentially allowing it to cope with nutrient stress in the surrounding of hydrothermal vents, providing the first genomic evidence for the carboxydotrophy in Thermococcus. VL - 190 SN - 0021-9193, 1098-5530 ER - TY - JOUR T1 - Computational Analysis of Constraints on Noncoding Regions, Coding Regions and Gene Expression in Relation to Plasmodium Phenotypic Diversity JF - PLoS ONEPLoS ONEPLoS ONEPLoS ONE Y1 - 2008 A1 - Essien, Kobby A1 - Sridhar Hannenhalli A1 - Stoeckert, Christian J. AB - Malaria-causing Plasmodium species exhibit marked differences including host choice and preference for invading particular cell types. The genetic bases of phenotypic differences between parasites can be understood, in part, by investigating constraints on gene expression and genic sequences, both coding and regulatory.We investigated the evolutionary constraints on sequence and expression of parasitic genes by applying comparative genomics approaches to 6 Plasmodium genomes and 2 genome-wide expression studies. We found that the coding regions of Plasmodium transcription factor and sexual development genes are relatively less constrained, as are those of genes encoding CCCH zinc fingers and invasion proteins, which all play important roles in these parasites. Transcription factors and genes with stage-restricted expression have conserved upstream regions and so do several gene classes critical to the parasite's lifestyle, namely, ion transport, invasion, chromatin assembly and CCCH zinc fingers. Additionally, a cross-species comparison of expression patterns revealed that Plasmodium-specific genes exhibit significant expression divergence. Overall, constraints on Plasmodium's protein coding regions confirm observations from other eukaryotes in that transcription factors are under relatively lower constraint. Proteins relevant to the parasite's unique lifestyle also have lower constraint on their coding regions. Greater conservation between Plasmodium species in terms of promoter motifs suggests tight regulatory control of lifestyle genes. However, an interspecies divergence in expression patterns of these genes suggests that either expression is controlled via genomic or epigenomic features not encoded in the proximal promoter sequence, or alternatively, the combinatorial interactions between motifs confer species-specific expression patterns. VL - 3 ER - TY - JOUR T1 - Covariability of Vibrio Cholerae Microdiversity and Environmental Parameters JF - Applied and Environmental MicrobiologyAppl. Environ. Microbiol.Applied and Environmental MicrobiologyAppl. Environ. Microbiol. Y1 - 2008 A1 - Zo, Young-Gun A1 - Chokesajjawatee, Nipa A1 - Arakawa, Eiji A1 - Watanabe, Haruo A1 - Huq, Anwar A1 - Rita R. Colwell AB - Fine-scale diversity of natural bacterial assemblages has been attributed to neutral radiation because correspondence between bacterial phylogenetic signals in the natural environment and environmental parameters had not been detected. Evidence that such correspondence occurs is provided for Vibrio cholerae, establishing a critical role for environmental parameters in bacterial diversity. VL - 74 SN - 0099-2240, 1098-5336 ER - TY - JOUR T1 - Determination of Clonality and Relatedness of Vibrio Cholerae Isolates by Genomic Fingerprinting, Using Long-Range Repetitive Element Sequence-Based PCR JF - Applied and Environmental MicrobiologyAppl. Environ. Microbiol.Applied and Environmental MicrobiologyAppl. Environ. Microbiol. Y1 - 2008 A1 - Chokesajjawatee, Nipa A1 - Zo, Young-Gun A1 - Rita R. Colwell AB - A high-throughput method which is applicable for rapid screening, identification, and delineation of isolates of Vibrio cholerae, sensitive to genome variation, and capable of providing phylogenetic inferences enhances environmental monitoring of this bacterium. We have developed and optimized a method for genomic fingerprinting of V. cholerae based on long-range PCR. The method uses a primer set directed to enterobacterial repetitive intergenic consensus sequences, a high-fidelity DNA polymerase, and analysis via conventional agarose gel electrophoresis. Long (∼10 kb), highly reproducible amplicons were generated from V. cholerae isolates, including those from different geographical locations and historical strains isolated during the period 1931-2000. The amplicons yielded reduced variability in their densitometric band patterns to ≤10% and clonal distinction at <90% similarity. Rapid band-matching analysis was accomplished for fingerprints with ≥90% similarity, discriminating O serotypes and biotypes (classical versus El Tor) as well as pathogenic and nonpathogenic strains. Compared to genome similarity measured by DNA-DNA hybridization, the results showed good correlation (r = 0.7; P < 0.001), with five times less measurement error and without bias. The method permits both phylogenetic inference and clonal differentiation of individual V. cholerae strains, enables robust, high-throughput analysis, and does not require specialized equipment to perform. With access to a curated public database furnished with appropriate analytical software applications, the method should prove useful in large-scale multilaboratory surveys, especially those designed to detect specific pathogens in the natural environment. VL - 74 SN - 0099-2240, 1098-5336 ER - TY - JOUR T1 - The draft genome of the transgenic tropical fruit tree papaya (Carica papaya Linnaeus). JF - Nature Y1 - 2008 A1 - Ming, Ray A1 - Hou, Shaobin A1 - Feng, Yun A1 - Yu, Qingyi A1 - Dionne-Laporte, Alexandre A1 - Saw, Jimmy H A1 - Senin, Pavel A1 - Wang, Wei A1 - Ly, Benjamin V A1 - Lewis, Kanako L T A1 - Salzberg, Steven L A1 - Feng, Lu A1 - Jones, Meghan R A1 - Skelton, Rachel L A1 - Murray, Jan E A1 - Chen, Cuixia A1 - Qian, Wubin A1 - Shen, Junguo A1 - Du, Peng A1 - Eustice, Moriah A1 - Tong, Eric A1 - Tang, Haibao A1 - Lyons, Eric A1 - Paull, Robert E A1 - Michael, Todd P A1 - Wall, Kerr A1 - Rice, Danny W A1 - Albert, Henrik A1 - Wang, Ming-Li A1 - Zhu, Yun J A1 - Schatz, Michael A1 - Nagarajan, Niranjan A1 - Acob, Ricelle A A1 - Guan, Peizhu A1 - Blas, Andrea A1 - Wai, Ching Man A1 - Ackerman, Christine M A1 - Ren, Yan A1 - Liu, Chao A1 - Wang, Jianmei A1 - Wang, Jianping A1 - Na, Jong-Kuk A1 - Shakirov, Eugene V A1 - Haas, Brian A1 - Thimmapuram, Jyothi A1 - Nelson, David A1 - Wang, Xiyin A1 - Bowers, John E A1 - Gschwend, Andrea R A1 - Delcher, Arthur L A1 - Singh, Ratnesh A1 - Suzuki, Jon Y A1 - Tripathi, Savarni A1 - Neupane, Kabi A1 - Wei, Hairong A1 - Irikura, Beth A1 - Paidi, Maya A1 - Jiang, Ning A1 - Zhang, Wenli A1 - Presting, Gernot A1 - Windsor, Aaron A1 - Navajas-Pérez, Rafael A1 - Torres, Manuel J A1 - Feltus, F Alex A1 - Porter, Brad A1 - Li, Yingjun A1 - Burroughs, A Max A1 - Luo, Ming-Cheng A1 - Liu, Lei A1 - Christopher, David A A1 - Mount, Stephen M A1 - Moore, Paul H A1 - Sugimura, Tak A1 - Jiang, Jiming A1 - Schuler, Mary A A1 - Friedman, Vikki A1 - Mitchell-Olds, Thomas A1 - Shippen, Dorothy E A1 - dePamphilis, Claude W A1 - Palmer, Jeffrey D A1 - Freeling, Michael A1 - Paterson, Andrew H A1 - Gonsalves, Dennis A1 - Wang, Lei A1 - Alam, Maqsudul KW - Arabidopsis KW - Carica KW - Contig Mapping KW - Databases, Genetic KW - Genes, Plant KW - Genome, Plant KW - Molecular Sequence Data KW - Plants, Genetically Modified KW - sequence alignment KW - Sequence Analysis, DNA KW - Transcription Factors KW - Tropical Climate AB -

Papaya, a fruit crop cultivated in tropical and subtropical regions, is known for its nutritional benefits and medicinal applications. Here we report a 3x draft genome sequence of 'SunUp' papaya, the first commercial virus-resistant transgenic fruit tree to be sequenced. The papaya genome is three times the size of the Arabidopsis genome, but contains fewer genes, including significantly fewer disease-resistance gene analogues. Comparison of the five sequenced genomes suggests a minimal angiosperm gene set of 13,311. A lack of recent genome duplication, atypical of other angiosperm genomes sequenced so far, may account for the smaller papaya gene number in most functional groups. Nonetheless, striking amplifications in gene number within particular functional groups suggest roles in the evolution of tree-like habit, deposition and remobilization of starch reserves, attraction of seed dispersal agents, and adaptation to tropical daylengths. Transgenesis at three locations is closely associated with chloroplast insertions into the nuclear genome, and with topoisomerase I recognition sites. Papaya offers numerous advantages as a system for fruit-tree functional genomics, and this draft genome sequence provides the foundation for revealing the basis of Carica's distinguishing morpho-physiological, medicinal and nutritional properties.

VL - 452 CP - 7190 M3 - 10.1038/nature06856 ER - TY - JOUR T1 - Dual role colonization factors connecting Vibrio cholerae's lifestyles in human and aquatic environments open new perspectives for combating infectious diseases JF - Current Opinion in BiotechnologyCurrent Opinion in Biotechnology Y1 - 2008 A1 - Vezzulli, Luigi A1 - Guzmán, Carlos A. A1 - Rita R. Colwell A1 - Pruzzo, Carla AB - Vibrio cholerae exhibits two distinctive lifestyles, one inside the milieu of the human intestine and the other in the aquatic environment. Recently, the existence of V. cholerae ligands involved in colonization of both human intestine and environmental chitin surfaces via the same binding specificity has been shown. Such molecules, here named ‘dual role colonization factors (DRCFs)’, are example of a tight connection between the two V. cholerae's lifestyles. It is suggested that DRCFs and, more generally, bacterial factors and pathways having roles in pathogenesis and in the out of the human body life may be promising targets for development of novel prophylactic or therapeutic interventions that may also affect V. cholerae fitness in its environmental reservoirs. VL - 19 SN - 0958-1669 ER - TY - JOUR T1 - Environmental signatures associated with cholera epidemics JF - Proceedings of the National Academy of SciencesProceedings of the National Academy of Sciences Y1 - 2008 A1 - Constantin de Magny, G. A1 - Murtugudde, R. A1 - Sapiano, M. R. P. A1 - Nizam, A. A1 - Brown, C. W. A1 - Busalacchi, A. J. A1 - Yunus, M. A1 - Nair, G. B. A1 - Gil, A. I. A1 - Lanata, C. F. A1 - Rita R. Colwell AB - The causative agent of cholera, Vibrio cholerae, has been shown to be autochthonous to riverine, estuarine, and coastal waters along with its host, the copepod, a significant member of the zooplankton community. Temperature, salinity, rainfall and plankton have proven to be important factors in the ecology of V. cholerae, influencing the transmission of the disease in those regions of the world where the human population relies on untreated water as a source of drinking water. In this study, the pattern of cholera outbreaks during 1998–2006 in Kolkata, India, and Matlab, Bangladesh, and the earth observation data were analyzed with the objective of developing a prediction model for cholera. Satellite sensors were used to measure chlorophyll a concentration (CHL) and sea surface temperature (SST). In addition, rainfall data were obtained from both satellite and in situ gauge measurements. From the analyses, a statistically significant relationship between the time series for cholera in Kolkata, India, and CHL and rainfall anomalies was determined. A statistically significant one month lag was observed between CHL anomaly and number of cholera cases in Matlab, Bangladesh. From the results of the study, it is concluded that ocean and climate patterns are useful predictors of cholera epidemics, with the dynamics of endemic cholera being related to climate and/or changes in the aquatic ecosystem. When the ecology of V. cholerae is considered in predictive models, a robust early warning system for cholera in endemic regions of the world can be developed for public health planning and decision making.ecology epidemiology microbiology remote sensing VL - 105 SN - 0027-8424, 1091-6490 ER - TY - JOUR T1 - Environmental Vibrio spp., isolated in Mozambique, contain a polymorphic group of integrative conjugative elements and class 1 integrons JF - FEMS Microbiology EcologyFEMS Microbiology Ecology Y1 - 2008 A1 - Taviani, Elisa A1 - Ceccarelli, Daniela A1 - Lazaro, Nivalda A1 - Bani, Stefania A1 - Cappuccinelli, Piero A1 - Rita R. Colwell A1 - Colombo, Mauro M. KW - ICE KW - integron KW - Mozambique KW - Vibrio AB - Circulation of mobile genetic elements linked to drug resistance spread was studied in Vibrio strains isolated from surface urban water (river and sea) and shellfish samples in 2002–2003 in Maputo, Mozambique. Class 1 integrons and integrating conjugative elements (ICE) were investigated by PCR and mating experiments in strains of major health interest: 10 Vibrio cholerae, six Vibrio parahaemolyticus, two Vibrio alginolyticus and one Vibrio fluvialis. Resistance to at least two antibiotics (predominantly β-lactams) was detected in all the strains, with additional resistances to sulfamethoxazole, spectinomycin, streptomycin and/or trimethoprim. Class 1 integrons contributed partially to the expression of drug resistance and were found in five isolates: four V. cholerae (blaP1 cassette, one strain also contained the dfrA15 cassette) and one V. alginolyticus (aadA2 cassette). ICEs, apparently devoid of resistance genes, were found in eight V. cholerae, three V. parahaemolyticus and one V. fluvialis isolates. A wide variability was observed by molecular characterization of ICEs. Five ICEs were included in the SXT/R391 family and seven ICEs were not classified. Our results indicate that the SXT/R391 family and related ICEs comprise a large class of polymorphic genetic elements widely circulating in environmental Vibrio strains in Africa, beside those evidently linked to drug resistance in clinical isolates. VL - 64 SN - 1574-6941 ER - TY - RPRT T1 - Estimating Tree-Structured Covariance Matrices via Mixed-Integer Programming with an Application to Phylogenetic Analysis of Gene Expression Y1 - 2008 A1 - Héctor Corrada Bravo A1 - Eng, K. H. A1 - Keles, S. A1 - Wahba, G. A1 - Wright, S. AB - We present a novel method for estimating tree-structured covariance matrices directly fromobserved continuous data. A representation of these classes of matrices as linear combinations of rank-one matrices indicating object partitions is used to formulate estimation as instances of well-studied numerical optimization problems. In particular, we present estimation based on projection where the covariance estimate is the nearest tree-structured covariance matrix to an observed sample covariance matrix. The problem is posed as a linear or quadratic mixed-integer program (MIP) where a setting of the integer variables in the MIP specifies a set of tree topologies of the structured covariance matrix. We solve these problems to optimality using efficient and robust existing MIP solvers. We also show that the least squares distance method of Fitch and Margoliash (1967) can be formulated as a quadratic MIP and thus solved exactly using existing, robust branch-and-bound MIP solvers. Our motivation for this method is the discovery of phylogenetic structure directly from gene expression data. Recent studies have adapted traditional phylogenetic comparative anal- ysis methods to expression data. Typically, these methods first estimate a phylogenetic tree from genomic sequence data and subsequently analyze expression data. A covariance matrix constructed from the sequence-derived tree is used to correct for the lack of independence in phy- logenetically related taxa. However, recent results have shown that the hierarchical structure of sequence-derived tree estimates are highly sensitive to the genomic region chosen to build them. To circumvent this difficulty, we propose a stable method for deriving tree-structured covariance matrices directly from gene expression as an exploratory step that can guide investigators in their modelling choices for these types of comparative analysis. We present a case study in phylogenetic analysis of expression in yeast gene families. Our method is able to corroborate the presence of phylogenetic structure in the response of expression in a subset of the gene families under particular experimental conditions. Additionally, when used in conjunction with transcription factor occupancy data, our methods show that alternative modelling choices should be considered when creating sequence-derived trees for this comparative analysis. PB - Department of Statistics, University of Wisconsin VL - 1142 ER - TY - JOUR T1 - Eukaryotic Transcription Factor Binding Sites—modeling and Integrative Search Methods JF - BioinformaticsBioinformaticsBioinformaticsBioinformatics Y1 - 2008 A1 - Sridhar Hannenhalli AB - A comprehensive knowledge of transcription factor binding sites (TFBS) is important for a mechanistic understanding of transcriptional regulation as well as for inferring gene regulatory networks. Because the DNA motif recognized by a transcription factor is typically short and degenerate, computational approaches for identifying binding sites based only on the sequence motif inevitably suffer from high error rates. Current state-of-the-art techniques for improving computational identification of binding sites can be broadly categorized into two classes: (1) approaches that aim to improve binding motif models by extracting maximal sequence information from experimentally determined binding sites and (2) approaches that supplement binding motif models with additional genomic or other attributes (such as evolutionary conservation). In this review we will discuss recent attempts to improve computational identification of TFBS through these two types of approaches and conclude with thoughts on future development.Contact: sridharh@pcbi.upenn.edu VL - 24 SN - 1367-4803, 1460-2059 ER - TY - CHAP T1 - Expanding the reach of Grid computing: combining Globus- and BOINC-based systems T2 - Grids for Bioinformatics and Computational BiologyGrids for Bioinformatics and Computational Biology Y1 - 2008 A1 - Myers, D. S. A1 - Adam L. Bazinet A1 - Michael P. Cummings ED - Talbi, E. G. ED - Zomaya, A. Y. JA - Grids for Bioinformatics and Computational BiologyGrids for Bioinformatics and Computational Biology T3 - Wiley Book Series on Bioinformatics: Computational Techniques and Engineering PB - Wiley-Interscience CY - Hoboken ER - TY - JOUR T1 - Figaro: A Novel Statistical Method for Vector Sequence Removal JF - BioinformaticsBioinformaticsBioinformaticsBioinformatics Y1 - 2008 A1 - White, James Robert A1 - Roberts, Michael A1 - Yorke, James A. A1 - M. Pop AB - Motivation: Sequences produced by automated Sanger sequencing machines frequently contain fragments of the cloning vector on their ends. Software tools currently available for identifying and removing the vector sequence require knowledge of the vector sequence, specific splice sites and any adapter sequences used in the experiment—information often omitted from public databases. Furthermore, the clipping coordinates themselves are missing or incorrectly reported. As an example, within the ∼1.24 billion shotgun sequences deposited in the NCBI Trace Archive, as many as ∼735 million (∼60%) lack vector clipping information. Correct clipping information is essential to scientists attempting to validate, improve and even finish the increasingly large number of genomes released at a ‘draft’ quality level.Results: We present here Figaro, a novel software tool for identifying and removing the vector from raw sequence data without prior knowledge of the vector sequence. The vector sequence is automatically inferred by analyzing the frequency of occurrence of short oligo-nucleotides using Poisson statistics. We show that Figaro achieves 99.98% sensitivity when tested on ∼1.5 million shotgun reads from Drosophila pseudoobscura. We further explore the impact of accurate vector trimming on the quality of whole-genome assemblies by re-assembling two bacterial genomes from shotgun sequences deposited in the Trace Archive. Designed as a module in large computational pipelines, Figaro is fast, lightweight and flexible. Availability: Figaro is released under an open-source license through the AMOS package (http://amos.sourceforge.net/Figaro). Contact: mpop@umiacs.umd.edu VL - 24 SN - 1367-4803, 1460-2059 ER - TY - JOUR T1 - Functional Diversification of Paralogous Transcription Factors via Divergence in DNA Binding Site Motif and in Expression JF - PLoS ONEPLoS ONEPLoS ONEPLoS ONE Y1 - 2008 A1 - Singh, Larry N. A1 - Sridhar Hannenhalli AB - Gene duplication is a major driver of evolutionary innovation as it allows for an organism to elaborate its existing biological functions via specialization or diversification of initially redundant gene paralogs. Gene function can diversify in several ways. Transcription factor gene paralogs in particular, can diversify either by changes in their tissue-specific expression pattern or by changes in the DNA binding site motif recognized by their protein product, which in turn alters their gene targets. The relationship between these two modes of functional diversification of transcription factor paralogs has not been previously investigated, and is essential for understanding adaptive evolution of transcription factor gene families.Based on a large set of human paralogous transcription factor pairs, we show that when the DNA binding site motifs of transcription factor paralogs are similar, the expressions of the genes that encode the paralogs have diverged, so in general, at most one of the paralogs is highly expressed in a tissue. Moreover, paralogs with diverged DNA binding site motifs tend to be diverged in their function. Conversely, two paralogs that are highly expressed in a tissue tend to have dissimilar DNA binding site motifs. We have also found that in general, within a paralogous family, tissue-specific decrease in gene expression is more frequent than what is expected by chance. While previous investigations of paralogous gene diversification have only considered coding sequence divergence, by explicitly quantifying divergence in DNA binding site motif, our work presents a new paradigm for investigating functional diversification. Consistent with evolutionary expectation, our quantitative analysis suggests that paralogous transcription factors have survived extinction in part, either through diversification of their DNA binding site motifs or through alterations in their tissue-specific expression levels. VL - 3 ER - TY - JOUR T1 - A GENEALOGICAL APPROACH TO QUANTIFYING LINEAGE DIVERGENCE JF - EvolutionEvolution Y1 - 2008 A1 - Michael P. Cummings A1 - Neel, Maile C. A1 - Shaw, Kerry L. KW - Ancestral polymorphism KW - congruence KW - exclusivity KW - genealogy KW - lineage sorting KW - monophyly KW - paraphyly KW - Phylogeny KW - polyphyly KW - speciation KW - species AB - We introduce a statistic, the genealogical sorting index (gsi), for quantifying the degree of exclusive ancestry of labeled groups on a rooted genealogy and demonstrate its application. The statistic is simple, intuitive, and easily calculated. It has a normalized range to facilitate comparisons among different groups, trees, or studies and it provides information on individual groups rather than a composite measure for all groups. It naturally handles polytomies and accommodates measures of uncertainty in phylogenetic relationships. We use coalescent simulations to explore the behavior of the gsi across a range of divergence times, with the mean value increasing to 1, the maximum value when exclusivity within a group reached monophyly. Simulations also demonstrate that the power to reject the null hypothesis of mixed genealogical ancestry increased markedly as sample size increased, and that the gsi provides a statistically more powerful measure of divergence than FST. Applications to data from published studies demonstrated that the gsi provides a useful way to detect significant exclusivity even when groups are not monophyletic. Although we describe this statistic in the context of divergence, it is more broadly applicable to quantify and assess the significance of clustering of observations in labeled groups on any tree. VL - 62 SN - 1558-5646 ER - TY - JOUR T1 - Genome assembly forensics: finding the elusive mis-assembly JF - Genome BiologyGenome Biology Y1 - 2008 A1 - Phillippy, Adam M. A1 - Schatz, Michael C. A1 - M. Pop AB - We present the first collection of tools aimed at automated genome assembly validation. This work formalizes several mechanisms for detecting mis-assemblies, and describes their implementation in our automated validation pipeline, called amosvalidate. We demonstrate the application of our pipeline in both bacterial and eukaryotic genome assemblies, and highlight several assembly errors in both draft and finished genomes. The software described is compatible with common assembly formats and is released, open-source, at http://amos.sourceforge.net. VL - 9 SN - 1465-6906 ER - TY - JOUR T1 - Genome-Wide Analysis of Natural Selection on Human Cis-Elements JF - PLoS ONEPLoS ONEPLoS ONEPLoS ONE Y1 - 2008 A1 - Sethupathy, Praveen A1 - Giang, Hoa A1 - Plotkin, Joshua B. A1 - Sridhar Hannenhalli AB - It has been speculated that the polymorphisms in the non-coding portion of the human genome underlie much of the phenotypic variability among humans and between humans and other primates. If so, these genomic regions may be undergoing rapid evolutionary change, due in part to natural selection. However, the non-coding region is a heterogeneous mix of functional and non-functional regions. Furthermore, the functional regions are comprised of a variety of different types of elements, each under potentially different selection regimes.Using the HapMap and Perlegen polymorphism data that map to a stringent set of putative binding sites in human proximal promoters, we apply the Derived Allele Frequency distribution test of neutrality to provide evidence that many human-specific and primate-specific binding sites are likely evolving under positive selection. We also discuss inherent limitations of publicly available human SNP datasets that complicate the inference of selection pressures. Finally, we show that the genes whose proximal binding sites contain high frequency derived alleles are enriched for positive regulation of protein metabolism and developmental processes. Thus our genome-scale investigation provides evidence for positive selection on putative transcription factor binding sites in human proximal promoters. VL - 3 ER - TY - JOUR T1 - Genome-wide analysis of repetitive elements in papaya JF - Tropical Plant BiologyTropical Plant Biology Y1 - 2008 A1 - Nagarajan, N. A1 - Navajas-Pérez, R. A1 - M. Pop A1 - Alam, M. A1 - Ming, R. A1 - Paterson, A. H. A1 - Salzberg, S. L. PB - Springer VL - 1 ER - TY - JOUR T1 - Global impact of Vibrio cholerae interactions with chitin JF - Environmental MicrobiologyEnvironmental Microbiology Y1 - 2008 A1 - Pruzzo, Carla A1 - Vezzulli, Luigi A1 - Rita R. Colwell AB - The interaction of Vibrio cholerae with chitin exemplifies for microbial ecology a successful bacteria–substrate interaction with complex and significant influence on the lifestyle of the bacterium. Chitin is one of the most abundant polymers on earth and possibly the most abundant in the aquatic environment, where its association with V. cholerae has provided the microorganism with a number of advantages, including food availability, adaptation to environmental nutrient gradients, tolerance to stress and protection from predators. Emergent properties of V. cholerae–chitin interactions occur at multiple hierarchical levels in the environment and include cell metabolic and physiological responses e.g. chemotaxis, cell multiplication, induction of competence, biofilm formation, commensal and symbiotic relationship with higher organisms, cycling of nutrients, and pathogenicity for humans and aquatic animals. As factors mediating virulence of V. cholerae for humans and aquatic animals derive from mechanisms of adaptation to its environment, at different levels of hierarchical scale, V. cholerae interactions with chitin represent a useful model for examination of the role of primary habitat selection in the development of traits that have been identified as virulence factors in human disease. VL - 10 SN - 1462-2920 ER - TY - JOUR T1 - Guest Editors' Introduction to the Special Section on Algorithms in Bioinformatics (WABI'07) JF - IEEE/ACM Transactions on Computational Biology and BioinformaticsIEEE/ACM Transactions on Computational Biology and Bioinformatics Y1 - 2008 A1 - Giancarlo, R. A1 - Sridhar Hannenhalli PB - IEEE Computer Society ER - TY - JOUR T1 - The impact of the neisserial DNA uptake sequences on genome evolution and stability JF - Genome biology Y1 - 2008 A1 - Todd Treangen A1 - Ambur, Ole Herman A1 - Tonjum, Tone A1 - Rocha, Eduardo PC VL - 9 ER - TY - CHAP T1 - The Lattice Project: a Grid research and production environment combining multiple Grid computing models T2 - Distributed & Grid Computing — Science Made Transparent for Everyone. Principles, Applications and Supporting CommunitiesDistributed & Grid Computing — Science Made Transparent for Everyone. Principles, Applications and Supporting Communities Y1 - 2008 A1 - Adam L. Bazinet A1 - Michael P. Cummings ED - Weber, M. H. W. JA - Distributed & Grid Computing — Science Made Transparent for Everyone. Principles, Applications and Supporting CommunitiesDistributed & Grid Computing — Science Made Transparent for Everyone. Principles, Applications and Supporting Communities PB - Rechenkraft.net CY - Marburg ER - TY - BOOK T1 - Lecture Notes in Computer ScienceBioinformatics Research and ApplicationsGapped Extension for Local Multiple Alignment of Interspersed DNA Repeats Y1 - 2008 A1 - Todd Treangen A1 - Darling, Aaron E. A1 - Ragan, Mark A. A1 - Messeguer, Xavier PB - Springer Berlin Heidelberg CY - Berlin, Heidelberg VL - 4983 SN - 978-3-540-79449-3 UR - http://www.springerlink.com/index/10.1007/978-3-540-79450-9http://link.springer.com/10.1007/978-3-540-79450-9_8http://www.springerlink.com/index/pdf/10.1007/978-3-540-79450-9_8 M3 - 10.1007/978-3-540-79450-910.1007/978-3-540-79450-9_8 ER - TY - CHAP T1 - The marine environment and human health: the cholera model T2 - Global Climate Change and Extreme Weather Events: Understanding the Contributions to Infectious Disease EmergenceGlobal Climate Change and Extreme Weather Events: Understanding the Contributions to Infectious Disease Emergence Y1 - 2008 A1 - Rita R. Colwell ED - Relman, David JA - Global Climate Change and Extreme Weather Events: Understanding the Contributions to Infectious Disease EmergenceGlobal Climate Change and Extreme Weather Events: Understanding the Contributions to Infectious Disease Emergence PB - National Academies Press SN - 9780309124027 ER - TY - JOUR T1 - Maternal depletion of CTCF reveals multiple functions during oocyte and preimplantation embryo development JF - DevelopmentDevelopment Y1 - 2008 A1 - Wan, L. B. A1 - Pan, H. A1 - Sridhar Hannenhalli A1 - Cheng, Y. A1 - Ma, J. A1 - Fedoriw, A. A1 - Lobanenkov, V. A1 - Latham, K. E. A1 - Schultz, R. M. A1 - Bartolomei, M. S. PB - The Company of Biologists Limited VL - 135 ER - TY - JOUR T1 - The minimum information about a genome sequence (MIGS) specification JF - Nature biotechnologyNature biotechnology Y1 - 2008 A1 - Field, Dawn A1 - Garrity, George A1 - Gray, Tanya A1 - Morrison, Norman A1 - J. Selengut A1 - Sterk, Peter A1 - Tatusova, Tatiana A1 - Thomson, Nicholas A1 - Allen, Michael J. A1 - Angiuoli, Samuel V. A1 - Ashburner, Michael A1 - Axelrod, Nelson A1 - Baldauf, Sandra A1 - Ballard, Stuart A1 - Boore, Jeffrey A1 - Cochrane, Guy A1 - Cole, James A1 - Dawyndt, Peter A1 - De Vos, Paul A1 - DePamphilis, Claude A1 - Edwards, Robert A1 - Faruque, Nadeem A1 - Feldman, Robert A1 - Gilbert, Jack A1 - Gilna, Paul A1 - Glöckner, Frank Oliver A1 - Goldstein, Philip A1 - Guralnick, Robert A1 - Haft, Dan A1 - Hancock, David A1 - Hermjakob, Henning A1 - Hertz-Fowler, Christiane A1 - Hugenholtz, Phil A1 - Joint, Ian A1 - Kagan, Leonid A1 - Kane, Matthew A1 - Kennedy, Jessie A1 - Kowalchuk, George A1 - Kottmann, Renzo A1 - Kolker, Eugene A1 - Kravitz, Saul A1 - Kyrpides, Nikos A1 - Leebens-Mack, Jim A1 - Lewis, Suzanna E. A1 - Li, Kelvin A1 - Lister, Allyson L. A1 - Lord, Phillip A1 - Maltsev, Natalia A1 - Markowitz, Victor A1 - Martiny, Jennifer A1 - Methe, Barbara A1 - Mizrachi, Ilene A1 - Moxon, Richard A1 - Nelson, Karen A1 - Parkhill, Julian A1 - Proctor, Lita A1 - White, Owen A1 - Sansone, Susanna-Assunta A1 - Spiers, Andrew A1 - Stevens, Robert A1 - Swift, Paul A1 - Taylor, Chris A1 - Tateno, Yoshio A1 - Tett, Adrian A1 - Turner, Sarah A1 - Ussery, David A1 - Vaughan, Bob A1 - Ward, Naomi A1 - Whetzel, Trish A1 - San Gil, Ingio A1 - Wilson, Gareth A1 - Wipat, Anil KW - Chromosome mapping KW - Databases, Factual KW - information dissemination KW - Information Storage and Retrieval KW - Information Theory KW - Internationality AB - With the quantity of genomic data increasing at an exponential rate, it is imperative that these data be captured electronically, in a standard format. Standardization activities must proceed within the auspices of open-access and international working bodies. To tackle the issues surrounding the development of better descriptions of genomic investigations, we have formed the Genomic Standards Consortium (GSC). Here, we introduce the minimum information about a genome sequence (MIGS) specification with the intent of promoting participation in its development and discussing the resources that will be required to develop improved mechanisms of metadata capture and exchange. As part of its wider goals, the GSC also supports improving the 'transparency' of the information contained in existing genomic databases. VL - 26 N1 - http://www.ncbi.nlm.nih.gov/pubmed/18464787?dopt=Abstract ER - TY - JOUR T1 - A molecular footprint of limb loss: sequence variation of the autopodial identity gene Hoxa-13 JF - J Mol EvolJ Mol Evol Y1 - 2008 A1 - Kohlsdorf, T. A1 - Michael P. Cummings A1 - Lynch, V. J. A1 - Stopper, G. F. A1 - Takahashi, K. A1 - Wagner, G. P. AB - The homeobox gene Hoxa-13 codes for a transcription factor involved in multiple functions, including body axis and hand/foot development in tetrapods. In this study we investigate whether the loss of one function (e.g., limb loss in snakes) left a molecular footprint in exon 1 of Hoxa-13 that could be associated with the release of functional constraints caused by limb loss. Fragments of the Hoxa-13 exon 1 were sequenced from 13 species and analyzed, with additional published sequences of the same region, using relative rates and likelihood-ratio tests. Five amino acid sites in exon 1 of Hoxa-13 were detected as evolving under positive selection in the stem lineage of snakes. To further investigate whether there is an association between limb loss and sequence variation in Hoxa-13, we used the random forest method on an alignment that included shark, basal fish lineages, and "eu-tetrapods" such as mammals, turtle, alligator, and birds. The random forest method approaches the problem as one of classification, where we seek to predict the presence or absence of autopodium based on amino acid variation in Hoxa-13 sequences. Different alignments tested were associated with similar error rates (18.42%). The random forest method suggested that phenotypic states (autopodium present and absent) can often be correctly predicted based on Hoxa-13 sequences. Basal, nontetrapod gnat-hostomes that never had an autopodium were consistently classified as limbless together with the snakes, while eu-tetrapods without any history of limb loss in their phylogeny were also consistently classified as having a limb. Misclassifications affected mostly lizards, which, as a group, have a history of limb loss and limb re-evolution, and the urodele and caecilian in our sample. We conclude that a molecular footprint can be detected in Hoxa-13 that is associated with the lack of an autopodium; groups with classification ambiguity (lizards) are characterized by a history of repeated limb loss and possible limb re-evolution. VL - 67 ER - TY - JOUR T1 - New records of phytoplankton for Bangladesh. 2. Cryptophyceae and Synurophyceae JF - Bangladesh Journal of BotanyBangladesh Journal of Botany Y1 - 2008 A1 - Khondker, Moniruzzaman A1 - Bhuiyan, Rauf Ahmed A1 - Yeasmin, Jenat A1 - Alam, Munirul A1 - Sack, R. Bradley A1 - Huq, Anwar A1 - Rita R. Colwell AB - This study presents two species of Rhodomonas, four species of Chroomonas, six species of Cryptomonas and Cryptochrysis minor, Cyanomonas coeruleus, Chrysodidymus synuroideus and Mallomonas akrokomos. These species have been reported from some ponds of Mathbaria in Pirojpur and Bakerganj of Barisal district in Bangladesh. VL - 36 SN - 0253-5416 ER - TY - JOUR T1 - New records of phytoplankton for Bangladesh. 5. Euglena, Euglenocapsa JF - Bangladesh Journal of Plant TaxonomyBangladesh Journal of Plant Taxonomy Y1 - 2008 A1 - Khondker, Moniruzzaman A1 - Bhuiyan, Rauf Ahmed A1 - Yeasmin, Jenat A1 - Alam, Munirul A1 - Sack, R. Bradley A1 - Huq, Anwar A1 - Rita R. Colwell AB - This study presents 20 taxa of the genus Euglena and one species of the rare euglenoid genus Euglenocapsa. All these taxa are reported for the first time from some pond ecosystems of Mathbaria in Pirojpur and Bakerganj of Barisal districts of Bangladesh. VL - 15 SN - 1028-2092 ER - TY - JOUR T1 - New records of phytoplankton for Bangladesh. 7. Phacus spp JF - Bangladesh Journal of BotanyBangladesh Journal of Botany Y1 - 2008 A1 - Khondker, Moniruzzaman A1 - Bhuiyan, Rauf Ahmed A1 - Yeasmin, Jenat A1 - Alam, Munirul A1 - Sack, R. Bradley A1 - Huq, Anwar A1 - Rita R. Colwell AB - Thirteen species of Phacus hitherto not reported from Bangladesh have been described and illustrated. Freshwater ponds at southern districts of Pirojpur and Barisal revealed these presence of the species. VL - 37 SN - 0253-5416 ER - TY - JOUR T1 - New records of phytoplankton for Bangladesh. 8. Trachelomonas Ehr. (Euglenophyceae) JF - Bangladesh Journal of BotanyBangladesh Journal of Botany Y1 - 2008 A1 - Khondker, Moniruzzaman A1 - Bhuiyan, Rauf Ahmed A1 - Yeasmin, Jenat A1 - Alam, Munirul A1 - Sack, R. Bradley A1 - Huq, Anwar A1 - Rita R. Colwell AB - Investigation of pelagic plankton communities from some freshwater ponds of Pirojpur and Barisal districts revealed the presence of 17 species under the genus Trachelomonas Ehr. for the first time in Bangladesh. VL - 37 SN - 0253-5416 ER - TY - JOUR T1 - Occurrence and Expression of Luminescence in Vibrio Cholerae JF - Applied and Environmental MicrobiologyAppl. Environ. Microbiol.Applied and Environmental MicrobiologyAppl. Environ. Microbiol. Y1 - 2008 A1 - Grim, Christopher J. A1 - Taviani, Elisa A1 - Alam, Munirul A1 - Huq, Anwar A1 - Sack, R. Bradley A1 - Rita R. Colwell AB - Several species of the genus Vibrio, including Vibrio cholerae, are bioluminescent or contain bioluminescent strains. Previous studies have reported that only 10% of V. cholerae strains are luminescent. Analysis of 224 isolates of non-O1/non-O139 V. cholerae collected from Chesapeake Bay, MD, revealed that 52% (116/224) were luminescent when an improved assay method was employed and 58% (130/224) of isolates harbored the luxA gene. In contrast, 334 non-O1/non-O139 V. cholerae strains isolated from two rural provinces in Bangladesh yielded only 21 (6.3%) luminescent and 35 (10.5%) luxA+ isolates. An additional 270 clinical and environmental isolates of V. cholerae serogroups O1 and O139 were tested, and none were luminescent or harbored luxA. These results indicate that bioluminescence may be a trait specific for non-O1/non-O139 V. cholerae strains that frequently occur in certain environments. Luminescence expression patterns of V. cholerae were also investigated, and isolates could be grouped based on expression level. Several strains with defective expression of the lux operon, including natural K variants, were identified. VL - 74 SN - 0099-2240, 1098-5336 ER - TY - JOUR T1 - Resolving arthropod phylogeny: exploring phylogenetic signal within 41 kb of protein-coding nuclear gene sequence JF - Syst BiolSyst Biol Y1 - 2008 A1 - Regier, J. C. A1 - Shultz, J. W. A1 - Ganley, A. R. D. A1 - Hussey, A. A1 - Shi, D. A1 - Ball, B. A1 - Zwick, A. A1 - Stajich, J. E. A1 - Michael P. Cummings A1 - Martin, J. W. A1 - Cunningham, C. W. AB - This study attempts to resolve relationships among and within the four basal arthropod lineages (Pancrustacea, Myriapoda, Euchelicerata, Pycnogonida) and to assess the widespread expectation that remaining phylogenetic problems will yield to increasing amounts of sequence data. Sixty-eight regions of 62 protein-coding nuclear genes (approximately 41 kilobases (kb)/taxon) were sequenced for 12 taxonomically diverse arthropod taxa and a tardigrade outgroup. Parsimony, likelihood, and Bayesian analyses of total nucleotide data generally strongly supported the monophyly of each of the basal lineages represented by more than one species. Other relationships within the Arthropoda were also supported, with support levels depending on method of analysis and inclusion/exclusion of synonymous changes. Removing third codon positions, where the assumption of base compositional homogeneity was rejected, altered the results. Removing the final class of synonymous mutations–first codon positions encoding leucine and arginine, which were also compositionally heterogeneous–yielded a data set that was consistent with a hypothesis of base compositional homogeneity. Furthermore, under such a data-exclusion regime, all 68 gene regions individually were consistent with base compositional homogeneity. Restricting likelihood analyses to nonsynonymous change recovered trees with strong support for the basal lineages but not for other groups that were variably supported with more inclusive data sets. In a further effort to increase phylogenetic signal, three types of data exploration were undertaken. (1) Individual genes were ranked by their average rate of nonsynonymous change, and three rate categories were assigned–fast, intermediate, and slow. Then, bootstrap analysis of each gene was performed separately to see which taxonomic groups received strong support. Five taxonomic groups were strongly supported independently by two or more genes, and these genes mostly belonged to the slow or intermediate categories, whereas groups supported only by a single gene region tended to be from genes of the fast category, arguing that fast genes provide a less consistent signal. (2) A sensitivity analysis was performed in which increasing numbers of genes were excluded, beginning with the fastest. The number of strongly supported nodes increased up to a point and then decreased slightly. Recovery of Hexapoda required removal of fast genes. Support for Mandibulata (Pancrustacea + Myriapoda) also increased, at times to "strong" levels, with removal of the fastest genes. (3) Concordance selection was evaluated by clustering genes according to their ability to recover Pancrustacea, Euchelicerata, or Myriapoda and analyzing the three clusters separately. All clusters of genes recovered the three concordance clades but were at times inconsistent in the relationships recovered among and within these clades, a result that indicates that the a priori concordance criteria may bias phylogenetic signal in unexpected ways. In a further attempt to increase support of taxonomic relationships, sequence data from 49 additional taxa for three slow genes (i.e., EF-1 alpha, EF-2, and Pol II) were combined with the various 13-taxon data sets. The 62-taxon analyses supported the results of the 13-taxon analyses and provided increased support for additional pancrustacean clades found in an earlier analysis including only EF-1 alpha, EF-2, and Pol II. VL - 57 ER - TY - JOUR T1 - Role of transposable elements in trypanosomatids JF - Microbes and InfectionMicrobes and Infection Y1 - 2008 A1 - Bringaud, Frederic A1 - Ghedin, Elodie A1 - Najib M. El‐Sayed A1 - Papadopoulou, Barbara KW - Cellular function KW - Domestication KW - Evolution KW - Gene expression KW - Leishmania KW - Regulation of mRNA stability KW - Retroposon KW - Transposable element KW - Trypanosoma AB - Transposable elements constitute 2-5% of the genome content in trypanosomatid parasites. Some of them are involved in critical cellular functions, such as the regulation of gene expression in Leishmania spp. In this review, we highlight the remarkable role extinct transposable elements can play as the source of potential new functions. VL - 10 SN - 1286-4579 ER - TY - JOUR T1 - Scaffolding and Validation of Bacterial Genome Assemblies Using Optical Restriction Maps JF - BioinformaticsBioinformaticsBioinformaticsBioinformatics Y1 - 2008 A1 - Nagarajan, Niranjan A1 - Read, Timothy D. A1 - M. Pop AB - Motivation: New, high-throughput sequencing technologies have made it feasible to cheaply generate vast amounts of sequence information from a genome of interest. The computational reconstruction of the complete sequence of a genome is complicated by specific features of these new sequencing technologies, such as the short length of the sequencing reads and absence of mate-pair information. In this article we propose methods to overcome such limitations by incorporating information from optical restriction maps.Results: We demonstrate the robustness of our methods to sequencing and assembly errors using extensive experiments on simulated datasets. We then present the results obtained by applying our algorithms to data generated from two bacterial genomes Yersinia aldovae and Yersinia kristensenii. The resulting assemblies contain a single scaffold covering a large fraction of the respective genomes, suggesting that the careful use of optical maps can provide a cost-effective framework for the assembly of genomes. Availability: The tools described here are available as an open-source package at ftp://ftp.cbcb.umd.edu/pub/software/soma Contact: mpop@umiacs.umd.edu VL - 24 SN - 1367-4803, 1460-2059 ER - TY - JOUR T1 - Schistosoma mansoni: Microarray analysis of gene expression induced by host sex. JF - Exp Parasitol Y1 - 2008 A1 - Waisberg, M A1 - Lobo, F P A1 - Cerqueira, G C A1 - Passos, L K J A1 - Carvalho, O S A1 - El-Sayed, N M A1 - Franco, G R KW - Animals KW - Biomphalaria KW - Female KW - Gene expression KW - Host-Parasite Interactions KW - Male KW - Mice KW - Oligonucleotide Array Sequence Analysis KW - Reverse Transcriptase Polymerase Chain Reaction KW - RNA, Helminth KW - Schistosoma mansoni KW - Schistosomiasis mansoni KW - Sex Factors AB -

Schistosoma mansoni is a digenetic trematode and a human parasite responsible for high social and economic impact. Although some authors have studied the effect of host hormones on parasites, not much is known about the effects of host sex on gene expression in Schistosomes. In order to study gene transcripts associated with the host sex, we compared the gene expression profiles of both male and female unisexual adult S. mansoni parasites raised on either male or female hosts, using DNA microarrays. Our results show that host sex caused differential expression of at least 11 genes in female parasites and of 134 in male parasites. Of the differentially expressed genes in female worms, 10 were preferentially expressed in female worms from male mice, while of the 134 differentially expressed genes in male parasites, 79 (59%) were preferentially expressed in worms from female mice. Further investigation of the role of each of those genes will help understand better their importance in the pathogenesis of Schistosomiasis.

VL - 120 CP - 4 M3 - 10.1016/j.exppara.2008.09.005 ER - TY - JOUR T1 - Seasonal Cholera from Multiple Small Outbreaks, Rural Bangladesh JF - Emerging Infectious DiseasesEmerg Infect DisEmerging Infectious DiseasesEmerg Infect Dis Y1 - 2008 A1 - Stine, O. Colin A1 - Alam, Munirul A1 - Tang, Li A1 - Nair, G. Balakrish A1 - Siddique, A. Kasem A1 - Faruque, Shah M. A1 - Huq, Anwar A1 - Rita R. Colwell A1 - Sack, R. Bradley A1 - Morris, J. Glenn AB - Clinical and environmental Vibrio cholerae organisms collected from February 2004 through April 2005 were systematically isolated from 2 rural Bangladeshi locales. Their genetic relatedness was evaluated at 5 loci that contained a variable number of tandem repeats (VNTR). The observed minimal overlap in VNTR patterns between the 2 communities was consistent with sequential, small outbreaks from local sources. VL - 14 SN - 1080-6040 ER - TY - JOUR T1 - Sequence diversity and evolution of multigene families in Trypanosoma cruzi JF - Molecular and Biochemical ParasitologyMolecular and Biochemical Parasitology Y1 - 2008 A1 - Cerqueira, Gustavo C. A1 - Bartholomeu, Daniella C. A1 - DaRocha, Wanderson D. A1 - Hou, Lihua A1 - Freitas-Silva, Danielle M. A1 - Machado, Carlos Renato A1 - Najib M. El‐Sayed A1 - Teixeira, Santuza M. R. KW - Amastin KW - Gene conversion KW - Genetic diversity KW - Multigene families KW - Trypanosoma cruzi AB - Several copies of genes belonging to three multigene families present in the genome of Trypanosoma cruzi were sequenced and comparatively analyzed across six different strains of the parasite belonging to the T. cruzi I lineage (Colombiana, Silvio X10 and Dm28c), the T. cruzi II lineage (Esmeraldo and JG) and a hybrid strain (CL Brener). For all three gene families analyzed, our results support the division in T. cruzi I and II lineages. Furthermore, in agreement with its hybrid nature, sequences derived from the CL Brener clone clustered together with T. cruzi II sequences as well as with a third group of sequences. Paralogous sequences encoding Amastin, an amastigote surface glycoprotein and TcAG48, an antigenic RNA binding protein, which are clustered in the parasite genome, present higher intragenomic variability in T. cruzi II and CL Brener strains, when compared to T. cruzi I strains. Paralogous sequences derived from the TcADC gene family, which encode various isoforms of adenylyl cyclases and are dispersed throughout the T. cruzi genome, exhibit similar degree of variability in all strains, except in the CL Brener strain, in which the sequences were more divergent. Several factors including mutation rates and gene conversion mechanisms, acting differently within the T. cruzi population, may contribute to create such distinct levels of sequence diversity in multigene families that are clustered in the T. cruzi genome. VL - 157 SN - 0166-6851 ER - TY - JOUR T1 - Sex and age dimorphism of myocardial gene expression in nonischemic human heart failure JF - Circulation: Cardiovascular GeneticsCirculation: Cardiovascular Genetics Y1 - 2008 A1 - Fermin, D. R. A1 - Barac, A. A1 - Lee, S. A1 - Polster, S. P. A1 - Sridhar Hannenhalli A1 - Bergemann, T. L. A1 - Grindle, S. A1 - Dyke, D. B. A1 - Pagani, F. A1 - Miller, L. W. A1 - others, PB - Am Heart Assoc VL - 1 ER - TY - JOUR T1 - Silent Sputnik JF - BioScienceBioScience Y1 - 2008 A1 - Rita R. Colwell VL - 58 SN - 0006-3568 ER - TY - JOUR T1 - A simple binomial test for estimating sequencing errors in public repository 16S rRNA sequences JF - Journal of Microbiological MethodsJournal of Microbiological Methods Y1 - 2008 A1 - Zo, Young-Gun A1 - Rita R. Colwell KW - 16S rRNA KW - Binomial model KW - Sequence similarity coefficient KW - Sequencing error KW - SSU rRNA AB - Sequences in public databases may contain a number of sequencing errors. A double binomial model describing the distribution of indel-excluded similarity coefficients (S) among repeatedly sequenced 16S rRNA was previously developed and it produced a confidence interval of S useful for testing sequence identity among sequences of 400-bp length. We characterized patterns in sequencing errors found in nearly complete 16S rRNA sequences of Vibrionaceae as highly variable in reported sequence length and containing a small number of indels. To accommodate these characteristics, a simple binomial model for distribution of the similarity coefficient (H) that included indels was derived from the double binomial model for S. The model showed good fit to empirical data. By using either a pre-determined or bootstrapping estimated standard probability of base matching, we were able to use the exact binomial test to determine the relative level of sequencing error for a given pair of duplicated sequences. A limitation of the method is the requirement that duplicated sequences for the same template sequence be paired, but this can be overcome by using only conserved regions of 16S rRNA sequences and pairing a given sequence with its highest scoring BLAST search hit from the nr database of GenBank. VL - 72 SN - 0167-7012 ER - TY - JOUR T1 - Transesterification activity of a novel lipase from Acinetobacter venetianus RAG-1 JF - Antonie van LeeuwenhoekAntonie van Leeuwenhoek Y1 - 2008 A1 - Snellman, E. A. A1 - Rita R. Colwell AB - Transesterification activity and the industrial potential of a novel lipase prepared from Acinetobacter ventiatus RAG-1 were evaluated. Purified lipase samples were dialyzed against pH 9.0 buffer in a single optimization step prior to lyophilization. The enzyme and organic phase were pre-equilibrated (separately) to the same thermodynamic water activities (a w) ranging from a w 0.33 to 0.97. Production of 1-octyl butyrate by lipase-catalyzed transesterification of vinyl butyrate with 1-octanol in hexane was monitored by gas chromatography. Production of 1-octyl butyrate and initial rate of reaction depended on water activity. Product synthesis and rate of transesterification increased sharply with increase from a w 0.33 to 0.55. Highest product concentration (218 mM) and rate of reaction (18.7 μmol h−1 · 10 μg protein) were measured at a w 0.86. Transesterification activity in hexane represented 32% of comparable hydrolytic activity in aqueous buffer. VL - 94 ER - TY - JOUR T1 - A Tutorial of the Poisson Random Field Model in Population Genetics JF - Advances in BioinformaticsAdvances in Bioinformatics Y1 - 2008 A1 - Sethupathy, Praveen A1 - Sridhar Hannenhalli AB - Population genetics is the study of allele frequency changes driven by various evolutionary forces such as mutation, natural selection, and random genetic drift. Although natural selection is widely recognized as a bona-fide phenomenon, the extent to which it drives evolution continues to remain unclear and controversial. Various qualitative techniques, or so-called “tests of neutrality”, have been introduced to detect signatures of natural selection. A decade and a half ago, Stanley Sawyer and Daniel Hartl provided a mathematical framework, referred to as the Poisson random field (PRF), with which to determine quantitatively the intensity of selection on a particular gene or genomic region. The recent availability of large-scale genetic polymorphism data has sparked widespread interest in genome-wide investigations of natural selection. To that end, the original PRF model is of particular interest for geneticists and evolutionary genomicists. In this article, we will provide a tutorial of the mathematical derivation of the original Sawyer and Hartl PRF model. VL - 2008 SN - 1687-8027, 1687-8035 ER - TY - Generic T1 - Uncovering Genomic Reassortments among Influenza Strains by Enumerating Maximal Bicliques T2 - IEEE International Conference on Bioinformatics and Biomedicine, 2008. BIBM '08 Y1 - 2008 A1 - Nagarajan, N. A1 - Kingsford, Carl KW - avian hosted influenza genome KW - Bioinformatics KW - Capacitive sensors KW - Delay KW - diseases KW - Event detection KW - general bipartite graphs KW - genomic reassortments KW - Genomics KW - graph theory KW - high probability inconsistencies KW - History KW - human hosted influenza genome KW - incompatibility graph KW - Influenza KW - influenza strain KW - maximal biclique KW - maximal biclique enumeration KW - microorganisms KW - phylogenetic trees KW - Phylogeny KW - Public healthcare KW - quadratic delay algorithm KW - reassortment KW - reassortment event detection KW - Tree graphs KW - viral genome evolutionary history KW - virulence AB - The evolutionary histories of viral genomes have received significant recent attention due to their importance in understanding virulence and the corresponding ramifications to public health. We present a novel framework to detect reassortment events in influenza based on the comparison of two distributions of phylogenetic trees, rather than a pair of, possibly unreliable, consensus trees. We show how to detect all high-probability inconsistencies between two distributions of trees by enumerating maximal bicliques within a defined incompatibility graph. In the process, we give the first quadratic delay algorithm for enumerating maximal bicliques within general bipartite graphs. We demonstrate the utility of our approach by applying it to several sets of influenza genomes (both human- and avian-hosted) and successfully identify all known reassortment events and a few novel candidate reassortments. In addition, on simulated datasets, our approach correctly finds implanted reassortments and rarely detects reassortments where none were introduced. JA - IEEE International Conference on Bioinformatics and Biomedicine, 2008. BIBM '08 PB - IEEE SN - 978-0-7695-3452-7 ER - TY - JOUR T1 - Vibrio cholerae non‐O1, non‐O139 strains isolated before 1992 from Varanasi, India are multiple drug resistant, contain intSXT, dfr18 and aadA5 genes JF - Environmental MicrobiologyEnvironmental Microbiology Y1 - 2008 A1 - Mohapatra, Harapriya A1 - Mohapatra, Saswat S. A1 - Mantri, Chinmay K. A1 - Rita R. Colwell A1 - Singh, Durg V. AB - In this study, we report the presence of the SXT element and Class I integron in Vibrio cholerae non-O1, non-O139 strains isolated from Varanasi, India. Isolates were resistant to cotrimoxazole, trimethoprim and/or streptomycin, furazolidone and ampicillin. None contained plasmids. Polymerase chain reaction (PCR) and DNA sequencing revealed the presence of antibiotic resistance gene cassettes, aadA1, aadA2, aadA5 and dfrA15, in the Class I integron and SXT, an integrative conjugative element containing dfr18, sulII and strAB, in three and six of the isolates respectively. Conjugation experiments, followed by PCR analysis of transconjugants, provided evidence for the transferable nature of intSXT and associated antibiotic resistance gene cassettes. This is the first report of the occurrence of SXT ICE, dfr18, sulII, strAB and aadA5 genes in environmental V. cholerae non-O1, non-O139 strains from Varanasi, India, that had been isolated before 1992. VL - 10 SN - 1462-2920 ER - TY - JOUR T1 - What are decision trees? JF - Nature biotechnologyNature biotechnology Y1 - 2008 A1 - Kingsford, Carl A1 - Salzberg, S. L. VL - 26 ER - TY - BOOK T1 - Algorithms in Bioinformatics: 7th International Workshop, WABI 2007, Philadelphia, PA, USA, September 8-9, 2007, Proceedings Y1 - 2007 A1 - Giancarlo, R. A1 - Sridhar Hannenhalli PB - Springer VL - 4645 ER - TY - JOUR T1 - Analyzing patterns of microbial evolution using the mauve genome alignment system JF - Comparative Genomics Y1 - 2007 A1 - Darling, Aaron E A1 - Todd Treangen A1 - Messeguer, Xavier A1 - Perna, Nicole T ER - TY - JOUR T1 - Association of Vibrio Cholerae O1 El Tor and O139 Bengal with the Copepods Acartia Tonsa and Eurytemora Affinis JF - Applied and Environmental MicrobiologyAppl. Environ. Microbiol.Applied and Environmental MicrobiologyAppl. Environ. Microbiol. Y1 - 2007 A1 - Rawlings, Tonya K. A1 - Ruiz, Gregory M. A1 - Rita R. Colwell AB - The association of Vibrio cholerae with zooplankton has been suggested as an important factor in transmission of human epidemic cholera, and the ability to colonize zooplankton surfaces may play a role in the temporal variation and predominance of the two different serogroups (V. cholerae O1 El Tor and O139) in the aquatic environment. To date, interactions between specific serogroups and species of plankton remain poorly understood. Laboratory microcosm experiments were carried out to compare quantitatively the colonization of two copepod species, Acartia tonsa and Eurytemora affinis, by each of the epidemic serogroups. V. cholerae O1 consistently achieved higher abundances than V. cholerae O139 in colonizing adults of each copepod species as well as the multiple life stages of E. affinis. This difference in colonization may be significant in the general predominance of V. cholerae O1 in cholera epidemics in rural Bangladesh where water supplies are taken directly from the environment. VL - 73 SN - 0099-2240, 1098-5336 ER - TY - JOUR T1 - Biased data reduce efficiency and effectiveness of conservation reserve networks JF - Ecology LettersEcology Letters Y1 - 2007 A1 - Grand, Joanna A1 - Michael P. Cummings A1 - Rebelo, Tony G. A1 - Ricketts, Taylor H. A1 - Neel, Maile C. KW - Bias KW - biodiversity conservation KW - complementarity KW - efficiency KW - marxan KW - rarity KW - reserve networks KW - reserve selection algorithms KW - species detection AB - Complementarity-based reserve selection algorithms efficiently prioritize sites for biodiversity conservation, but they are data-intensive and most regions lack accurate distribution maps for the majority of species. We explored implications of basing conservation planning decisions on incomplete and biased data using occurrence records of the plant family Proteaceae in South Africa. Treating this high-quality database as ‘complete’, we introduced three realistic sampling biases characteristic of biodiversity databases: a detectability sampling bias and two forms of roads sampling bias. We then compared reserve networks constructed using complete, biased, and randomly sampled data. All forms of biased sampling performed worse than both the complete data set and equal-effort random sampling. Biased sampling failed to detect a median of 1–5% of species, and resulted in reserve networks that were 9–17% larger than those designed with complete data. Spatial congruence and the correlation of irreplaceability scores between reserve networks selected with biased and complete data were low. Thus, reserve networks based on biased data require more area to protect fewer species and identify different locations than those selected with randomly sampled or complete data. VL - 10 SN - 1461-0248 ER - TY - JOUR T1 - Bio-STEER: A Semantic Web workflow tool for Grid computing in the life sciences JF - Future Generation Comp SystFuture Generation Comp Syst Y1 - 2007 A1 - Lee, S. A1 - Wang, T. D. A1 - Hashmi, N. A1 - Michael P. Cummings KW - client/server KW - distributed KW - ENVIRONMENTS KW - integrated KW - interface KW - management KW - semantics KW - services KW - systems KW - user KW - web-base KW - workflow AB - Life science research is becoming evermore computationally intensive. Hence, from a computational resource perspective, Grid computing provides a logical approach to meeting many of the computational needs of life science research. However, there are several barriers to the widespread use of Grid computing in life sciences. In this paper, we attempt to address one particular barrier: the difficulty of using Grid computing by life scientists. Life science research often involves connecting multiple applications together to form a workflow. This process of constructing a workflow is complex. When combined with the difficulty of using Grid services, composing a meaningful workflow using Grid services can present a challenge to life scientists. Our proposed solution is a Semantic Web-enabled computing environment, called Bio-STEER. In BioSTEER, bioinformatics Grid services are mapped to Semantic Web services, described in OWL-S. We also defined an ontology in OWL to model bioinformatics applications. A graphical user interface helps to construct a scientific workflow by showing a list of services that are semantically sound: that is, the output of one service is semantically compatible with the input of the connecting service. Bio-STEER can help users take full advantaue of Grid services through a user-friendly graphical user interface (GUI), which allows them to easily construct the workflows they need. (c) 2006 Elsevier B.V. All rights reserved. VL - 23 ER - TY - Generic T1 - Bridging art and science with creativity support tools T2 - Proceedings of the 6th ACM SIGCHI conference on Creativity & cognition Y1 - 2007 A1 - Shneiderman, Ben A1 - Rita R. Colwell A1 - Diamond, Sara A1 - Greenhalgh, Paul A1 - Wulf, William JA - Proceedings of the 6th ACM SIGCHI conference on Creativity & cognition T3 - C&C '07 PB - ACM CY - New York, NY, USA SN - 978-1-59593-712-4 ER - TY - JOUR T1 - Characterization of Ehp, a Secreted Complement Inhibitory Protein from Staphylococcus aureus JF - Journal of Biological ChemistryJournal of Biological Chemistry Y1 - 2007 A1 - Hammel, Michal A1 - Sfyroera, Georgia A1 - Pyrpassopoulos, Serapion A1 - Ricklin, Daniel A1 - Ramyar, Kasra X. A1 - M. Pop A1 - Jin, Zhongmin A1 - Lambris, John D. A1 - Geisbrecht, Brian V. AB - We report here the discovery and characterization of Ehp, a new secreted Staphylococcus aureus protein that potently inhibits the alternative complement activation pathway. Ehp was identified through a genomic scan as an uncharacterized secreted protein from S. aureus, and immunoblotting of conditioned S. aureus culture medium revealed that the Ehp protein was secreted at the highest levels during log-phase bacterial growth. The mature Ehp polypeptide is composed of 80 residues and is 44% identical to the complement inhibitory domain of S. aureus Efb (extracellular fibrinogen-binding protein). We observed preferential binding by Ehp to native and hydrolyzed C3 relative to fully active C3b and found that Ehp formed a subnanomolar affinity complex with these various forms of C3 by binding to its thioester-containing C3d domain. Site-directed mutagenesis demonstrated that Arg75 and Asn82 are important in forming the Ehp·C3d complex, but loss of these side chains did not completely disrupt Ehp/C3d binding. This suggested the presence of a second C3d-binding site in Ehp, which was mapped to the proximity of Ehp Asn63. Further molecular level details of the Ehp/C3d interaction were revealed by solving the 2.7-Å crystal structure of an Ehp·C3d complex in which the low affinity site had been mutationally inactivated. Ehp potently inhibited C3b deposition onto sensitized surfaces by the alternative complement activation pathway. This inhibition was directly related to Ehp/C3d binding and was more potent than that seen for Efb-C. An altered conformation in Ehp-bound C3 was detected by monoclonal antibody C3-9, which is specific for a neoantigen exposed in activated forms of C3. Our results suggest that increased inhibitory potency of Ehp relative to Efb-C is derived from the second C3-binding site in this new protein. VL - 282 ER - TY - JOUR T1 - Cofactor-independent phosphoglycerate mutase is an essential gene in procyclic form Trypanosoma brucei JF - Parasitology researchParasitology research Y1 - 2007 A1 - Djikeng, A. A1 - Raverdy, S. A1 - Foster, Jeffrey S. A1 - Bartholomeu, D. A1 - Zhang, Y. A1 - Najib M. El‐Sayed A1 - Carlow, C. VL - 100 ER - TY - JOUR T1 - COMPUTATIONAL BIOLOGY JF - Nucleic acids researchNucleic Acids Research Y1 - 2007 A1 - Leparc, G. G. A1 - Mitra, R. D. A1 - Vardhanabhuti, S. A1 - Wang, J. A1 - Sridhar Hannenhalli A1 - Smit, S. A1 - Widmann, J. A1 - Knight, R. A1 - Wu, S. A1 - Zhang, Y. A1 - others, PB - Information Retrieval Ltd VL - 35 ER - TY - JOUR T1 - A computational survey of candidate exonic splicing enhancer motifs in the model plant Arabidopsis thaliana. JF - BMC Bioinformatics Y1 - 2007 A1 - Pertea, Mihaela A1 - Mount, Stephen M A1 - Salzberg, Steven L KW - Alternative Splicing KW - Arabidopsis KW - Computational Biology KW - Enhancer Elements, Genetic KW - Exons KW - Genes, Plant KW - RNA, Plant AB -

BACKGROUND: Algorithmic approaches to splice site prediction have relied mainly on the consensus patterns found at the boundaries between protein coding and non-coding regions. However exonic splicing enhancers have been shown to enhance the utilization of nearby splice sites.

RESULTS: We have developed a new computational technique to identify significantly conserved motifs involved in splice site regulation. First, 84 putative exonic splicing enhancer hexamers are identified in Arabidopsis thaliana. Then a Gibbs sampling program called ELPH was used to locate conserved motifs represented by these hexamers in exonic regions near splice sites in confirmed genes. Oligomers containing 35 of these motifs have been shown experimentally to induce significant inclusion of A. thaliana exons. Second, integration of our regulatory motifs into two different splice site recognition programs significantly improved the ability of the software to correctly predict splice sites in a large database of confirmed genes. We have released GeneSplicerESE, the improved splice site recognition code, as open source software.

CONCLUSION: Our results show that the use of the ESE motifs consistently improves splice site prediction accuracy.

VL - 8 M3 - 10.1186/1471-2105-8-159 ER - TY - JOUR T1 - Creating a nationwide wireless detection sensor network for chemical, biological and radiological threats JF - Gentag White PaperGentag White Paper Y1 - 2007 A1 - Rita R. Colwell A1 - Peeters, J. ER - TY - JOUR T1 - Draft genome of the filarial nematode parasite Brugia malayi JF - ScienceScience Y1 - 2007 A1 - Ghedin, E. A1 - Wang, S. A1 - Spiro, D. A1 - Caler, E. A1 - Zhao, Q. A1 - Crabtree, J. A1 - Allen, J. E. A1 - Delcher, A. L. A1 - Guiliano, D. B. A1 - Miranda-Saavedra, D. A1 - others, PB - American Association for the Advancement of Science VL - 317 ER - TY - JOUR T1 - Eukaryotic Transcriptional Regulation: Signals, Interactions, and Modules JF - Computational Genomics: Current MethodsComputational Genomics: Current Methods Y1 - 2007 A1 - Sridhar Hannenhalli PB - Taylor & Francis ER - TY - JOUR T1 - Evolution of genes and genomes on the Drosophila phylogeny JF - NatureNature Y1 - 2007 A1 - Clark, Andrew G. A1 - Eisen, Michael B. A1 - Smith, Douglas R. A1 - Bergman, Casey M. A1 - Oliver, Brian A1 - Markow, Therese A. A1 - Kaufman, Thomas C. A1 - Kellis, Manolis A1 - Gelbart, William A1 - Iyer, Venky N. A1 - Pollard, Daniel A. A1 - Sackton, Timothy B. A1 - Larracuente, Amanda M. A1 - Singh, Nadia D. A1 - Abad, Jose P. A1 - Abt, Dawn N. A1 - Adryan, Boris A1 - Aguade, Montserrat A1 - Akashi, Hiroshi A1 - Anderson, Wyatt W. A1 - Aquadro, Charles F. A1 - Ardell, David H. A1 - Arguello, Roman A1 - Artieri, Carlo G. A1 - Barbash, Daniel A. A1 - Barker, Daniel A1 - Barsanti, Paolo A1 - Batterham, Phil A1 - Batzoglou, Serafim A1 - Begun, Dave A1 - Bhutkar, Arjun A1 - Blanco, Enrico A1 - Bosak, Stephanie A. A1 - Bradley, Robert K. A1 - Brand, Adrianne D. A1 - Brent, Michael R. A1 - Brooks, Angela N. A1 - Brown, Randall H. A1 - Butlin, Roger K. A1 - Caggese, Corrado A1 - Calvi, Brian R. A1 - Carvalho, A. Bernardo de A1 - Caspi, Anat A1 - Castrezana, Sergio A1 - Celniker, Susan E. A1 - Chang, Jean L. A1 - Chapple, Charles A1 - Chatterji, Sourav A1 - Chinwalla, Asif A1 - Civetta, Alberto A1 - Clifton, Sandra W. A1 - Comeron, Josep M. A1 - Costello, James C. A1 - Coyne, Jerry A. A1 - Daub, Jennifer A1 - David, Robert G. A1 - Delcher, Arthur L. A1 - Delehaunty, Kim A1 - Do, Chuong B. A1 - Ebling, Heather A1 - Edwards, Kevin A1 - Eickbush, Thomas A1 - Evans, Jay D. A1 - Filipski, Alan A1 - Findei, A1 - Sven A1 - Freyhult, Eva A1 - Fulton, Lucinda A1 - Fulton, Robert A1 - Garcia, Ana C. L. A1 - Gardiner, Anastasia A1 - Garfield, David A. A1 - Garvin, Barry E. A1 - Gibson, Greg A1 - Gilbert, Don A1 - Gnerre, Sante A1 - Godfrey, Jennifer A1 - Good, Robert A1 - Gotea, Valer A1 - Gravely, Brenton A1 - Greenberg, Anthony J. A1 - Griffiths-Jones, Sam A1 - Gross, Samuel A1 - Guigo, Roderic A1 - Gustafson, Erik A. A1 - Haerty, Wilfried A1 - Hahn, Matthew W. A1 - Halligan, Daniel L. A1 - Halpern, Aaron L. A1 - Halter, Gillian M. A1 - Han, Mira V. A1 - Heger, Andreas A1 - Hillier, LaDeana A1 - Hinrichs, Angie S. A1 - Holmes, Ian A1 - Hoskins, Roger A. A1 - Hubisz, Melissa J. A1 - Hultmark, Dan A1 - Huntley, Melanie A. A1 - Jaffe, David B. A1 - Jagadeeshan, Santosh A1 - Jeck, William R. A1 - Johnson, Justin A1 - Jones, Corbin D. A1 - Jordan, William C. A1 - Karpen, Gary H. A1 - Kataoka, Eiko A1 - Keightley, Peter D. A1 - Kheradpour, Pouya A1 - Kirkness, Ewen F. A1 - Koerich, Leonardo B. A1 - Kristiansen, Karsten A1 - Kudrna, Dave A1 - Kulathinal, Rob J. A1 - Kumar, Sudhir A1 - Kwok, Roberta A1 - Lander, Eric A1 - Langley, Charles H. A1 - Lapoint, Richard A1 - Lazzaro, Brian P. A1 - Lee, So-Jeong A1 - Levesque, Lisa A1 - Li, Ruiqiang A1 - Lin, Chiao-Feng A1 - Lin, Michael F. A1 - Lindblad-Toh, Kerstin A1 - Llopart, Ana A1 - Long, Manyuan A1 - Low, Lloyd A1 - Lozovsky, Elena A1 - Lu, Jian A1 - Luo, Meizhong A1 - Machado, Carlos A. A1 - Makalowski, Wojciech A1 - Marzo, Mar A1 - Matsuda, Muneo A1 - Matzkin, Luciano A1 - McAllister, Bryant A1 - McBride, Carolyn S. A1 - McKernan, Brendan A1 - McKernan, Kevin A1 - Mendez-Lago, Maria A1 - Minx, Patrick A1 - Mollenhauer, Michael U. A1 - Montooth, Kristi A1 - Stephen M. Mount A1 - Mu, Xu A1 - Myers, Eugene A1 - Negre, Barbara A1 - Newfeld, Stuart A1 - Nielsen, Rasmus A1 - Noor, Mohamed A. F. A1 - O'Grady, Patrick A1 - Pachter, Lior A1 - Papaceit, Montserrat A1 - Parisi, Matthew J. A1 - Parisi, Michael A1 - Parts, Leopold A1 - Pedersen, Jakob S. A1 - Pesole, Graziano A1 - Phillippy, Adam M. A1 - Ponting, Chris P. A1 - M. Pop A1 - Porcelli, Damiano A1 - Powell, Jeffrey R. A1 - Prohaska, Sonja A1 - Pruitt, Kim A1 - Puig, Marta A1 - Quesneville, Hadi A1 - Ram, Kristipati Ravi A1 - Rand, David A1 - Rasmussen, Matthew D. A1 - Reed, Laura K. A1 - Reenan, Robert A1 - Reily, Amy A1 - Remington, Karin A. A1 - Rieger, Tania T. A1 - Ritchie, Michael G. A1 - Robin, Charles A1 - Rogers, Yu-Hui A1 - Rohde, Claudia A1 - Rozas, Julio A1 - Rubenfield, Marc J. A1 - Ruiz, Alfredo A1 - Russo, Susan A1 - Salzberg, Steven L. A1 - Sanchez-Gracia, Alejandro A1 - Saranga, David J. A1 - Sato, Hajime A1 - Schaeffer, Stephen W. A1 - Schatz, Michael C. A1 - Schlenke, Todd A1 - Schwartz, Russell A1 - Segarra, Carmen A1 - Singh, Rama S. A1 - Sirot, Laura A1 - Sirota, Marina A1 - Sisneros, Nicholas B. A1 - Smith, Chris D. A1 - Smith, Temple F. A1 - Spieth, John A1 - Stage, Deborah E. A1 - Stark, Alexander A1 - Stephan, Wolfgang A1 - Strausberg, Robert L. A1 - Strempel, Sebastian A1 - Sturgill, David A1 - Sutton, Granger A1 - Sutton, Granger G. A1 - Tao, Wei A1 - Teichmann, Sarah A1 - Tobari, Yoshiko N. A1 - Tomimura, Yoshihiko A1 - Tsolas, Jason M. A1 - Valente, Vera L. S. A1 - Venter, Eli A1 - Venter, J. Craig A1 - Vicario, Saverio A1 - Vieira, Filipe G. A1 - Vilella, Albert J. A1 - Villasante, Alfredo A1 - Walenz, Brian A1 - Wang, Jun A1 - Wasserman, Marvin A1 - Watts, Thomas A1 - Wilson, Derek A1 - Wilson, Richard K. A1 - Wing, Rod A. A1 - Wolfner, Mariana F. A1 - Wong, Alex A1 - Wong, Gane Ka-Shu A1 - Wu, Chung- I. A1 - Wu, Gabriel A1 - Yamamoto, Daisuke A1 - Yang, Hsiao-Pei A1 - Yang, Shiaw-Pyng A1 - Yorke, James A. A1 - Yoshida, Kiyohito A1 - Zdobnov, Evgeny A1 - Zhang, Peili A1 - Zhang, Yu A1 - Zimin, Aleksey V. A1 - Baldwin, Jennifer A1 - Abdouelleil, Amr A1 - Abdulkadir, Jamal A1 - Abebe, Adal A1 - Abera, Brikti A1 - Abreu, Justin A1 - Acer, St Christophe A1 - Aftuck, Lynne A1 - Alexander, Allen A1 - An, Peter A1 - Anderson, Erica A1 - Anderson, Scott A1 - Arachi, Harindra A1 - Azer, Marc A1 - Bachantsang, Pasang A1 - Barry, Andrew A1 - Bayul, Tashi A1 - Berlin, Aaron A1 - Bessette, Daniel A1 - Bloom, Toby A1 - Blye, Jason A1 - Boguslavskiy, Leonid A1 - Bonnet, Claude A1 - Boukhgalter, Boris A1 - Bourzgui, Imane A1 - Brown, Adam A1 - Cahill, Patrick A1 - Channer, Sheridon A1 - Cheshatsang, Yama A1 - Chuda, Lisa A1 - Citroen, Mieke A1 - Collymore, Alville A1 - Cooke, Patrick A1 - Costello, Maura A1 - D'Aco, Katie A1 - Daza, Riza A1 - Haan, Georgius De A1 - DeGray, Stuart A1 - DeMaso, Christina A1 - Dhargay, Norbu A1 - Dooley, Kimberly A1 - Dooley, Erin A1 - Doricent, Missole A1 - Dorje, Passang A1 - Dorjee, Kunsang A1 - Dupes, Alan A1 - Elong, Richard A1 - Falk, Jill A1 - Farina, Abderrahim A1 - Faro, Susan A1 - Ferguson, Diallo A1 - Fisher, Sheila A1 - Foley, Chelsea D. A1 - Franke, Alicia A1 - Friedrich, Dennis A1 - Gadbois, Loryn A1 - Gearin, Gary A1 - Gearin, Christina R. A1 - Giannoukos, Georgia A1 - Goode, Tina A1 - Graham, Joseph A1 - Grandbois, Edward A1 - Grewal, Sharleen A1 - Gyaltsen, Kunsang A1 - Hafez, Nabil A1 - Hagos, Birhane A1 - Hall, Jennifer A1 - Henson, Charlotte A1 - Hollinger, Andrew A1 - Honan, Tracey A1 - Huard, Monika D. A1 - Hughes, Leanne A1 - Hurhula, Brian A1 - Husby, M. Erii A1 - Kamat, Asha A1 - Kanga, Ben A1 - Kashin, Seva A1 - Khazanovich, Dmitry A1 - Kisner, Peter A1 - Lance, Krista A1 - Lara, Marcia A1 - Lee, William A1 - Lennon, Niall A1 - Letendre, Frances A1 - LeVine, Rosie A1 - Lipovsky, Alex A1 - Liu, Xiaohong A1 - Liu, Jinlei A1 - Liu, Shangtao A1 - Lokyitsang, Tashi A1 - Lokyitsang, Yeshi A1 - Lubonja, Rakela A1 - Lui, Annie A1 - MacDonald, Pen A1 - Magnisalis, Vasilia A1 - Maru, Kebede A1 - Matthews, Charles A1 - McCusker, William A1 - McDonough, Susan A1 - Mehta, Teena A1 - Meldrim, James A1 - Meneus, Louis A1 - Mihai, Oana A1 - Mihalev, Atanas A1 - Mihova, Tanya A1 - Mittelman, Rachel A1 - Mlenga, Valentine A1 - Montmayeur, Anna A1 - Mulrain, Leonidas A1 - Navidi, Adam A1 - Naylor, Jerome A1 - Negash, Tamrat A1 - Nguyen, Thu A1 - Nguyen, Nga A1 - Nicol, Robert A1 - Norbu, Choe A1 - Norbu, Nyima A1 - Novod, Nathaniel A1 - O'Neill, Barry A1 - Osman, Sahal A1 - Markiewicz, Eva A1 - Oyono, Otero L. A1 - Patti, Christopher A1 - Phunkhang, Pema A1 - Pierre, Fritz A1 - Priest, Margaret A1 - Raghuraman, Sujaa A1 - Rege, Filip A1 - Reyes, Rebecca A1 - Rise, Cecil A1 - Rogov, Peter A1 - Ross, Keenan A1 - Ryan, Elizabeth A1 - Settipalli, Sampath A1 - Shea, Terry A1 - Sherpa, Ngawang A1 - Shi, Lu A1 - Shih, Diana A1 - Sparrow, Todd A1 - Spaulding, Jessica A1 - Stalker, John A1 - Stange-Thomann, Nicole A1 - Stavropoulos, Sharon A1 - Stone, Catherine A1 - Strader, Christopher A1 - Tesfaye, Senait A1 - Thomson, Talene A1 - Thoulutsang, Yama A1 - Thoulutsang, Dawa A1 - Topham, Kerri A1 - Topping, Ira A1 - Tsamla, Tsamla A1 - Vassiliev, Helen A1 - Vo, Andy A1 - Wangchuk, Tsering A1 - Wangdi, Tsering A1 - Weiand, Michael A1 - Wilkinson, Jane A1 - Wilson, Adam A1 - Yadav, Shailendra A1 - Young, Geneva A1 - Yu, Qing A1 - Zembek, Lisa A1 - Zhong, Danni A1 - Zimmer, Andrew A1 - Zwirko, Zac A1 - Jaffe, David B. A1 - Alvarez, Pablo A1 - Brockman, Will A1 - Butler, Jonathan A1 - Chin, CheeWhye A1 - Gnerre, Sante A1 - Grabherr, Manfred A1 - Kleber, Michael A1 - Mauceli, Evan A1 - MacCallum, Iain AB - Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species. VL - 450 SN - 0028-0836 N1 - [szlig] ER - TY - JOUR T1 - Evolution of genes and genomes on the Drosophila phylogeny. JF - Nature Y1 - 2007 A1 - Clark, Andrew G A1 - Eisen, Michael B A1 - Smith, Douglas R A1 - Bergman, Casey M A1 - Oliver, Brian A1 - Markow, Therese A A1 - Kaufman, Thomas C A1 - Kellis, Manolis A1 - Gelbart, William A1 - Iyer, Venky N A1 - Pollard, Daniel A A1 - Sackton, Timothy B A1 - Larracuente, Amanda M A1 - Singh, Nadia D A1 - Abad, Jose P A1 - Abt, Dawn N A1 - Adryan, Boris A1 - Aguade, Montserrat A1 - Akashi, Hiroshi A1 - Anderson, Wyatt W A1 - Aquadro, Charles F A1 - Ardell, David H A1 - Arguello, Roman A1 - Artieri, Carlo G A1 - Barbash, Daniel A A1 - Barker, Daniel A1 - Barsanti, Paolo A1 - Batterham, Phil A1 - Batzoglou, Serafim A1 - Begun, Dave A1 - Bhutkar, Arjun A1 - Blanco, Enrico A1 - Bosak, Stephanie A A1 - Bradley, Robert K A1 - Brand, Adrianne D A1 - Brent, Michael R A1 - Brooks, Angela N A1 - Brown, Randall H A1 - Butlin, Roger K A1 - Caggese, Corrado A1 - Calvi, Brian R A1 - Bernardo de Carvalho, A A1 - Caspi, Anat A1 - Castrezana, Sergio A1 - Celniker, Susan E A1 - Chang, Jean L A1 - Chapple, Charles A1 - Chatterji, Sourav A1 - Chinwalla, Asif A1 - Civetta, Alberto A1 - Clifton, Sandra W A1 - Comeron, Josep M A1 - Costello, James C A1 - Coyne, Jerry A A1 - Daub, Jennifer A1 - David, Robert G A1 - Delcher, Arthur L A1 - Delehaunty, Kim A1 - Do, Chuong B A1 - Ebling, Heather A1 - Edwards, Kevin A1 - Eickbush, Thomas A1 - Evans, Jay D A1 - Filipski, Alan A1 - Findeiss, Sven A1 - Freyhult, Eva A1 - Fulton, Lucinda A1 - Fulton, Robert A1 - Garcia, Ana C L A1 - Gardiner, Anastasia A1 - Garfield, David A A1 - Garvin, Barry E A1 - Gibson, Greg A1 - Gilbert, Don A1 - Gnerre, Sante A1 - Godfrey, Jennifer A1 - Good, Robert A1 - Gotea, Valer A1 - Gravely, Brenton A1 - Greenberg, Anthony J A1 - Griffiths-Jones, Sam A1 - Gross, Samuel A1 - Guigo, Roderic A1 - Gustafson, Erik A A1 - Haerty, Wilfried A1 - Hahn, Matthew W A1 - Halligan, Daniel L A1 - Halpern, Aaron L A1 - Halter, Gillian M A1 - Han, Mira V A1 - Heger, Andreas A1 - Hillier, LaDeana A1 - Hinrichs, Angie S A1 - Holmes, Ian A1 - Hoskins, Roger A A1 - Hubisz, Melissa J A1 - Hultmark, Dan A1 - Huntley, Melanie A A1 - Jaffe, David B A1 - Jagadeeshan, Santosh A1 - Jeck, William R A1 - Johnson, Justin A1 - Jones, Corbin D A1 - Jordan, William C A1 - Karpen, Gary H A1 - Kataoka, Eiko A1 - Keightley, Peter D A1 - Kheradpour, Pouya A1 - Kirkness, Ewen F A1 - Koerich, Leonardo B A1 - Kristiansen, Karsten A1 - Kudrna, Dave A1 - Kulathinal, Rob J A1 - Kumar, Sudhir A1 - Kwok, Roberta A1 - Lander, Eric A1 - Langley, Charles H A1 - Lapoint, Richard A1 - Lazzaro, Brian P A1 - Lee, So-Jeong A1 - Levesque, Lisa A1 - Li, Ruiqiang A1 - Lin, Chiao-Feng A1 - Lin, Michael F A1 - Lindblad-Toh, Kerstin A1 - Llopart, Ana A1 - Long, Manyuan A1 - Low, Lloyd A1 - Lozovsky, Elena A1 - Lu, Jian A1 - Luo, Meizhong A1 - Machado, Carlos A A1 - Makalowski, Wojciech A1 - Marzo, Mar A1 - Matsuda, Muneo A1 - Matzkin, Luciano A1 - McAllister, Bryant A1 - McBride, Carolyn S A1 - McKernan, Brendan A1 - McKernan, Kevin A1 - Mendez-Lago, Maria A1 - Minx, Patrick A1 - Mollenhauer, Michael U A1 - Montooth, Kristi A1 - Mount, Stephen M A1 - Mu, Xu A1 - Myers, Eugene A1 - Negre, Barbara A1 - Newfeld, Stuart A1 - Nielsen, Rasmus A1 - Noor, Mohamed A F A1 - O'Grady, Patrick A1 - Pachter, Lior A1 - Papaceit, Montserrat A1 - Parisi, Matthew J A1 - Parisi, Michael A1 - Parts, Leopold A1 - Pedersen, Jakob S A1 - Pesole, Graziano A1 - Phillippy, Adam M A1 - Ponting, Chris P A1 - Pop, Mihai A1 - Porcelli, Damiano A1 - Powell, Jeffrey R A1 - Prohaska, Sonja A1 - Pruitt, Kim A1 - Puig, Marta A1 - Quesneville, Hadi A1 - Ram, Kristipati Ravi A1 - Rand, David A1 - Rasmussen, Matthew D A1 - Reed, Laura K A1 - Reenan, Robert A1 - Reily, Amy A1 - Remington, Karin A A1 - Rieger, Tania T A1 - Ritchie, Michael G A1 - Robin, Charles A1 - Rogers, Yu-Hui A1 - Rohde, Claudia A1 - Rozas, Julio A1 - Rubenfield, Marc J A1 - Ruiz, Alfredo A1 - Russo, Susan A1 - Salzberg, Steven L A1 - Sanchez-Gracia, Alejandro A1 - Saranga, David J A1 - Sato, Hajime A1 - Schaeffer, Stephen W A1 - Schatz, Michael C A1 - Schlenke, Todd A1 - Schwartz, Russell A1 - Segarra, Carmen A1 - Singh, Rama S A1 - Sirot, Laura A1 - Sirota, Marina A1 - Sisneros, Nicholas B A1 - Smith, Chris D A1 - Smith, Temple F A1 - Spieth, John A1 - Stage, Deborah E A1 - Stark, Alexander A1 - Stephan, Wolfgang A1 - Strausberg, Robert L A1 - Strempel, Sebastian A1 - Sturgill, David A1 - Sutton, Granger A1 - Sutton, Granger G A1 - Tao, Wei A1 - Teichmann, Sarah A1 - Tobari, Yoshiko N A1 - Tomimura, Yoshihiko A1 - Tsolas, Jason M A1 - Valente, Vera L S A1 - Venter, Eli A1 - Venter, J Craig A1 - Vicario, Saverio A1 - Vieira, Filipe G A1 - Vilella, Albert J A1 - Villasante, Alfredo A1 - Walenz, Brian A1 - Wang, Jun A1 - Wasserman, Marvin A1 - Watts, Thomas A1 - Wilson, Derek A1 - Wilson, Richard K A1 - Wing, Rod A A1 - Wolfner, Mariana F A1 - Wong, Alex A1 - Wong, Gane Ka-Shu A1 - Wu, Chung-I A1 - Wu, Gabriel A1 - Yamamoto, Daisuke A1 - Yang, Hsiao-Pei A1 - Yang, Shiaw-Pyng A1 - Yorke, James A A1 - Yoshida, Kiyohito A1 - Zdobnov, Evgeny A1 - Zhang, Peili A1 - Zhang, Yu A1 - Zimin, Aleksey V A1 - Baldwin, Jennifer A1 - Abdouelleil, Amr A1 - Abdulkadir, Jamal A1 - Abebe, Adal A1 - Abera, Brikti A1 - Abreu, Justin A1 - Acer, St Christophe A1 - Aftuck, Lynne A1 - Alexander, Allen A1 - An, Peter A1 - Anderson, Erica A1 - Anderson, Scott A1 - Arachi, Harindra A1 - Azer, Marc A1 - Bachantsang, Pasang A1 - Barry, Andrew A1 - Bayul, Tashi A1 - Berlin, Aaron A1 - Bessette, Daniel A1 - Bloom, Toby A1 - Blye, Jason A1 - Boguslavskiy, Leonid A1 - Bonnet, Claude A1 - Boukhgalter, Boris A1 - Bourzgui, Imane A1 - Brown, Adam A1 - Cahill, Patrick A1 - Channer, Sheridon A1 - Cheshatsang, Yama A1 - Chuda, Lisa A1 - Citroen, Mieke A1 - Collymore, Alville A1 - Cooke, Patrick A1 - Costello, Maura A1 - D'Aco, Katie A1 - Daza, Riza A1 - De Haan, Georgius A1 - DeGray, Stuart A1 - DeMaso, Christina A1 - Dhargay, Norbu A1 - Dooley, Kimberly A1 - Dooley, Erin A1 - Doricent, Missole A1 - Dorje, Passang A1 - Dorjee, Kunsang A1 - Dupes, Alan A1 - Elong, Richard A1 - Falk, Jill A1 - Farina, Abderrahim A1 - Faro, Susan A1 - Ferguson, Diallo A1 - Fisher, Sheila A1 - Foley, Chelsea D A1 - Franke, Alicia A1 - Friedrich, Dennis A1 - Gadbois, Loryn A1 - Gearin, Gary A1 - Gearin, Christina R A1 - Giannoukos, Georgia A1 - Goode, Tina A1 - Graham, Joseph A1 - Grandbois, Edward A1 - Grewal, Sharleen A1 - Gyaltsen, Kunsang A1 - Hafez, Nabil A1 - Hagos, Birhane A1 - Hall, Jennifer A1 - Henson, Charlotte A1 - Hollinger, Andrew A1 - Honan, Tracey A1 - Huard, Monika D A1 - Hughes, Leanne A1 - Hurhula, Brian A1 - Husby, M Erii A1 - Kamat, Asha A1 - Kanga, Ben A1 - Kashin, Seva A1 - Khazanovich, Dmitry A1 - Kisner, Peter A1 - Lance, Krista A1 - Lara, Marcia A1 - Lee, William A1 - Lennon, Niall A1 - Letendre, Frances A1 - LeVine, Rosie A1 - Lipovsky, Alex A1 - Liu, Xiaohong A1 - Liu, Jinlei A1 - Liu, Shangtao A1 - Lokyitsang, Tashi A1 - Lokyitsang, Yeshi A1 - Lubonja, Rakela A1 - Lui, Annie A1 - MacDonald, Pen A1 - Magnisalis, Vasilia A1 - Maru, Kebede A1 - Matthews, Charles A1 - McCusker, William A1 - McDonough, Susan A1 - Mehta, Teena A1 - Meldrim, James A1 - Meneus, Louis A1 - Mihai, Oana A1 - Mihalev, Atanas A1 - Mihova, Tanya A1 - Mittelman, Rachel A1 - Mlenga, Valentine A1 - Montmayeur, Anna A1 - Mulrain, Leonidas A1 - Navidi, Adam A1 - Naylor, Jerome A1 - Negash, Tamrat A1 - Nguyen, Thu A1 - Nguyen, Nga A1 - Nicol, Robert A1 - Norbu, Choe A1 - Norbu, Nyima A1 - Novod, Nathaniel A1 - O'Neill, Barry A1 - Osman, Sahal A1 - Markiewicz, Eva A1 - Oyono, Otero L A1 - Patti, Christopher A1 - Phunkhang, Pema A1 - Pierre, Fritz A1 - Priest, Margaret A1 - Raghuraman, Sujaa A1 - Rege, Filip A1 - Reyes, Rebecca A1 - Rise, Cecil A1 - Rogov, Peter A1 - Ross, Keenan A1 - Ryan, Elizabeth A1 - Settipalli, Sampath A1 - Shea, Terry A1 - Sherpa, Ngawang A1 - Shi, Lu A1 - Shih, Diana A1 - Sparrow, Todd A1 - Spaulding, Jessica A1 - Stalker, John A1 - Stange-Thomann, Nicole A1 - Stavropoulos, Sharon A1 - Stone, Catherine A1 - Strader, Christopher A1 - Tesfaye, Senait A1 - Thomson, Talene A1 - Thoulutsang, Yama A1 - Thoulutsang, Dawa A1 - Topham, Kerri A1 - Topping, Ira A1 - Tsamla, Tsamla A1 - Vassiliev, Helen A1 - Vo, Andy A1 - Wangchuk, Tsering A1 - Wangdi, Tsering A1 - Weiand, Michael A1 - Wilkinson, Jane A1 - Wilson, Adam A1 - Yadav, Shailendra A1 - Young, Geneva A1 - Yu, Qing A1 - Zembek, Lisa A1 - Zhong, Danni A1 - Zimmer, Andrew A1 - Zwirko, Zac A1 - Jaffe, David B A1 - Alvarez, Pablo A1 - Brockman, Will A1 - Butler, Jonathan A1 - Chin, CheeWhye A1 - Gnerre, Sante A1 - Grabherr, Manfred A1 - Kleber, Michael A1 - Mauceli, Evan A1 - MacCallum, Iain KW - Animals KW - Codon KW - DNA Transposable Elements KW - Drosophila KW - Drosophila Proteins KW - Evolution, Molecular KW - Gene Order KW - Genes, Insect KW - Genome, Insect KW - Genome, Mitochondrial KW - Genomics KW - Immunity KW - Multigene Family KW - Phylogeny KW - Reproduction KW - RNA, Untranslated KW - sequence alignment KW - Sequence Analysis, DNA KW - Synteny AB -

Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.

VL - 450 CP - 7167 M3 - 10.1038/nature06341 ER - TY - JOUR T1 - The Expression of a Plant-type Ferredoxin Redox System provides Molecular Evidence for a Plastid in the Early Dinoflagellate Perkinsus marinus JF - ProtistProtist Y1 - 2007 A1 - Stelter, Kathrin A1 - Najib M. El‐Sayed A1 - Seeber, Frank KW - Apicomplexa KW - ferredoxin KW - Perkinsozoa KW - plastid KW - transit peptide AB - Perkinsus marinus is a parasitic protozoan with a phylogenetic positioning between Apicomplexa and dinoflagellates. It is thus of interest for reconstructing the early evolution of eukaryotes, especially with regard to the acquisition of secondary plastids in these organisms. It is also an important pathogen of oysters, and the definition of parasite-specific metabolic pathways would be beneficial for the identification of efficient treatments for infected mollusks. Although these different scientific interests have resulted in the start of a genome project for this organism, it is still unknown whether P. marinus contains a plastid or plastid-like organelle like the related dinoflagellates and Apicomplexa. Here, we show that in vitro-cultivated parasites contain transcripts of the plant-type ferredoxin and its associated reductase. Both proteins are nuclear-encoded and possess N-terminal targeting sequences similar to those characterized in dinoflagellates. Since this redox pair is exclusively found in cyanobacteria and plastid-harboring organisms its presence also in P. marinus is highly indicative of a plastid. We also provide additional evidence for such an organelle by demonstrating pharmacological sensitivity to inhibitors of plastid-localized enzymes involved in fatty acid biosynthesis (e.g. acetyl-CoA carboxylase) and by detection of genes for three enzymes of plastid-localized isoprenoid biosynthesis (1-deoxy-D-xylulose 5-phosphate reductoisomerase, (E)-4-hydroxy-3-methyl-but-2-enyl diphosphate reductase, and (E)-4-hydroxy-3-methyl-but-2-enyl diphosphate synthase). VL - 158 SN - 1434-4610 ER - TY - JOUR T1 - Features generated for computational splice-site prediction correspond to functional elements JF - BMC BioinformaticsBMC Bioinformatics Y1 - 2007 A1 - Dogan, Rezarta Islamaj A1 - Getoor, Lise A1 - Wilbur, W. John A1 - Stephen M. Mount AB - BackgroundAccurate selection of splice sites during the splicing of precursors to messenger RNA requires both relatively well-characterized signals at the splice sites and auxiliary signals in the adjacent exons and introns. We previously described a feature generation algorithm (FGA) that is capable of achieving high classification accuracy on human 3' splice sites. In this paper, we extend the splice-site prediction to 5' splice sites and explore the generated features for biologically meaningful splicing signals. Results We present examples from the observed features that correspond to known signals, both core signals (including the branch site and pyrimidine tract) and auxiliary signals (including GGG triplets and exon splicing enhancers). We present evidence that features identified by FGA include splicing signals not found by other methods. Conclusion Our generated features capture known biological signals in the expected sequence interval flanking splice sites. The method can be easily applied to other species and to similar classification problems, such as tissue-specific regulatory elements, polyadenylation sites, promoters, etc. VL - 8 SN - 14712105 ER - TY - JOUR T1 - Features generated for computational splice-site prediction correspond to functional elements. JF - BMC Bioinformatics Y1 - 2007 A1 - Dogan, Rezarta Islamaj A1 - Getoor, Lise A1 - Wilbur, W John A1 - Mount, Stephen M KW - Computational Biology KW - HUMANS KW - Predictive Value of Tests KW - RNA Splice Sites KW - RNA, Messenger AB -

BACKGROUND: Accurate selection of splice sites during the splicing of precursors to messenger RNA requires both relatively well-characterized signals at the splice sites and auxiliary signals in the adjacent exons and introns. We previously described a feature generation algorithm (FGA) that is capable of achieving high classification accuracy on human 3' splice sites. In this paper, we extend the splice-site prediction to 5' splice sites and explore the generated features for biologically meaningful splicing signals.

RESULTS: We present examples from the observed features that correspond to known signals, both core signals (including the branch site and pyrimidine tract) and auxiliary signals (including GGG triplets and exon splicing enhancers). We present evidence that features identified by FGA include splicing signals not found by other methods.

CONCLUSION: Our generated features capture known biological signals in the expected sequence interval flanking splice sites. The method can be easily applied to other species and to similar classification problems, such as tissue-specific regulatory elements, polyadenylation sites, promoters, etc.

VL - 8 M3 - 10.1186/1471-2105-8-410 ER - TY - JOUR T1 - GATA and Nkx factors synergistically regulate tissue-specific gene expression and development in vivo JF - DevelopmentDevelopment Y1 - 2007 A1 - Zhang, Yuzhen A1 - Rath, Nibedita A1 - Sridhar Hannenhalli A1 - Wang, Zhishan A1 - Cappola, Thomas A1 - Kimura, Shioko A1 - Atochina-Vasserman, Elena A1 - Lu, Min Min A1 - Beers, Michael F. A1 - Morrisey, Edward E. AB - In vitro studies have suggested that members of the GATA and Nkx transcription factor families physically interact, and synergistically activate pulmonary epithelial- and cardiac-gene promoters. However, the relevance of this synergy has not been demonstrated in vivo. We show that Gata6-Titf1 (Gata6-Nkx2.1) double heterozygous (G6-Nkx DH) embryos and mice have severe defects in pulmonary epithelial differentiation and distal airway development, as well as reduced phospholipid production. The defects in G6-Nkx DH embryos and mice are similar to those observed in human neonates with respiratory distress syndromes, including bronchopulmonary dysplasia, and differential gene expression analysis reveals essential developmental pathways requiring synergistic regulation by both Gata6 and Titf1 (Nkx2.1). These studies indicate that Gata6 and Nkx2.1 act in a synergistic manner to direct pulmonary epithelial differentiation and development in vivo, providing direct evidence that interactions between these two transcription factor families are crucial for the development of the tissues in which they are co-expressed. VL - 134 ER - TY - JOUR T1 - Genome Analysis Linking Recent European and African Influenza (H5N1) Viruses JF - Emerging Infectious DiseasesEmerg Infect DisEmerging Infectious DiseasesEmerg Infect Dis Y1 - 2007 A1 - Salzberg, Steven L. A1 - Kingsford, Carl A1 - Cattoli, Giovanni A1 - Spiro, David J. A1 - Janies, Daniel A. A1 - Aly, Mona Mehrez A1 - Brown, Ian H. A1 - Couacy-Hymann, Emmanuel A1 - De Mia, Gian Mario A1 - Dung, Do Huu A1 - Guercio, Annalisa A1 - Joannis, Tony A1 - Ali, Ali Safar Maken A1 - Osmani, Azizullah A1 - Padalino, Iolanda A1 - Saad, Magdi D. A1 - Savić, Vladimir A1 - Sengamalay, Naomi A. A1 - Yingst, Samuel A1 - Zaborsky, Jennifer A1 - Zorman-Rojs, Olga A1 - Ghedin, Elodie A1 - Capua, Ilaria AB - Although linked, these viruses are distinct from earlier outbreak strains., To better understand the ecology and epidemiology of the highly pathogenic avian influenza virus in its transcontinental spread, we sequenced and analyzed the complete genomes of 36 recent influenza A (H5N1) viruses collected from birds in Europe, northern Africa, and southeastern Asia. These sequences, among the first complete genomes of influenza (H5N1) viruses outside Asia, clearly depict the lineages now infecting wild and domestic birds in Europe and Africa and show the relationships among these isolates and other strains affecting both birds and humans. The isolates fall into 3 distinct lineages, 1 of which contains all known non-Asian isolates. This new Euro-African lineage, which was the cause of several recent (2006) fatal human infections in Egypt and Iraq, has been introduced at least 3 times into the European-African region and has split into 3 distinct, independently evolving sublineages. One isolate provides evidence that 2 of these sublineages have recently reassorted. VL - 13 SN - 1080-6040 ER - TY - JOUR T1 - Genome sequence and identification of candidate vaccine antigens from the animal pathogen Dichelobacter nodosus. JF - Nat Biotechnol Y1 - 2007 A1 - Myers, Garry S A A1 - Parker, Dane A1 - Al-Hasani, Keith A1 - Kennan, Ruth M A1 - Seemann, Torsten A1 - Ren, Qinghu A1 - Badger, Jonathan H A1 - Selengut, Jeremy D A1 - DeBoy, Robert T A1 - Tettelin, Hervé A1 - Boyce, John D A1 - McCarl, Victoria P A1 - Han, Xiaoyan A1 - Nelson, William C A1 - Madupu, Ramana A1 - Mohamoud, Yasmin A1 - Holley, Tara A1 - Fedorova, Nadia A1 - Khouri, Hoda A1 - Bottomley, Steven P A1 - Whittington, Richard J A1 - Adler, Ben A1 - Songer, J Glenn A1 - Rood, Julian I A1 - Paulsen, Ian T KW - Animals KW - Antigens KW - Chromosome mapping KW - Dichelobacter nodosus KW - Foot Rot KW - Genome, Bacterial KW - Sequence Analysis, DNA AB -

Dichelobacter nodosus causes ovine footrot, a disease that leads to severe economic losses in the wool and meat industries. We sequenced its 1.4-Mb genome, the smallest known genome of an anaerobe. It differs markedly from small genomes of intracellular bacteria, retaining greater biosynthetic capabilities and lacking any evidence of extensive ongoing genome reduction. Comparative genomic microarray studies and bioinformatic analysis suggested that, despite its small size, almost 20% of the genome is derived from lateral gene transfer. Most of these regions seem to be associated with virulence. Metabolic reconstruction indicated unsuspected capabilities, including carbohydrate utilization, electron transfer and several aerobic pathways. Global transcriptional profiling and bioinformatic analysis enabled the prediction of virulence factors and cell surface proteins. Screening of these proteins against ovine antisera identified eight immunogenic proteins that are candidate antigens for a cross-protective vaccine.

VL - 25 CP - 5 M3 - 10.1038/nbt1302 ER - TY - JOUR T1 - Genome sequence and identification of candidate vaccine antigens from the animal pathogen Dichelobacter nodosus JF - Nature biotechnologyNature biotechnology Y1 - 2007 A1 - Myers, Garry S. A. A1 - Parker, Dane A1 - Al-Hasani, Keith A1 - Kennan, Ruth M. A1 - Seemann, Torsten A1 - Ren, Qinghu A1 - Badger, Jonathan H. A1 - J. Selengut A1 - DeBoy, Robert T. A1 - Tettelin, Hervé A1 - Boyce, John D. A1 - McCarl, Victoria P. A1 - Han, Xiaoyan A1 - Nelson, William C. A1 - Madupu, Ramana A1 - Mohamoud, Yasmin A1 - Holley, Tara A1 - Fedorova, Nadia A1 - Khouri, Hoda A1 - Bottomley, Steven P. A1 - Whittington, Richard J. A1 - Adler, Ben A1 - Songer, J. Glenn A1 - Rood, Julian I. A1 - Paulsen, Ian T. KW - Animals KW - Antigens KW - Chromosome mapping KW - Dichelobacter nodosus KW - Foot Rot KW - Genome, Bacterial KW - Sequence Analysis, DNA AB - Dichelobacter nodosus causes ovine footrot, a disease that leads to severe economic losses in the wool and meat industries. We sequenced its 1.4-Mb genome, the smallest known genome of an anaerobe. It differs markedly from small genomes of intracellular bacteria, retaining greater biosynthetic capabilities and lacking any evidence of extensive ongoing genome reduction. Comparative genomic microarray studies and bioinformatic analysis suggested that, despite its small size, almost 20% of the genome is derived from lateral gene transfer. Most of these regions seem to be associated with virulence. Metabolic reconstruction indicated unsuspected capabilities, including carbohydrate utilization, electron transfer and several aerobic pathways. Global transcriptional profiling and bioinformatic analysis enabled the prediction of virulence factors and cell surface proteins. Screening of these proteins against ovine antisera identified eight immunogenic proteins that are candidate antigens for a cross-protective vaccine. VL - 25 N1 - http://www.ncbi.nlm.nih.gov/pubmed/17468768?dopt=Abstract ER - TY - JOUR T1 - Genome-wide expression profiling and bioinformatics analysis of diurnally regulated genes in the mouse prefrontal cortex JF - Genome BiolGenome Biol Y1 - 2007 A1 - Yang, S. A1 - Wang, K. A1 - Valladares, O. A1 - Sridhar Hannenhalli A1 - Bucan, M. A1 - others, VL - 8 ER - TY - Generic T1 - A graph-based approach to vehicle tracking in traffic camera video streams T2 - Proceedings of the 4th workshop on Data management for sensor networks: in conjunction with 33rd International Conference on Very Large Data Bases Y1 - 2007 A1 - Shahri, Hamid Haidarian A1 - Namata, Galileo A1 - Navlakha, Saket A1 - Deshpande, Amol A1 - Roussopoulos, Nick AB - Vehicle tracking has a wide variety of applications from law enforcement to traffic planning and public safety. However, the image resolution of the videos available from most traffic camera systems, make it difficult to track vehicles based on unique identifiers like license plates. In many cases, vehicles with similar attributes are indistinguishable from one another due to image quality issues. Often, network bandwidth and power constraints limit the frame rate, as well. In this paper, we discuss the challenges of performing vehicle tracking queries over video streams from ubiquitous traffic cameras. We identify the limitations of tracking vehicles individually in such conditions and provide a novel graph-based approach using the identity of neighboring vehicles to improve the performance. We evaluate our approach using streaming video feeds from live traffic cameras available on the Internet. The results show that vehicle tracking is feasible, even for low quality and low frame rate traffic cameras. Additionally, exploitation of the attributes of neighboring vehicles significantly improves the performance. JA - Proceedings of the 4th workshop on Data management for sensor networks: in conjunction with 33rd International Conference on Very Large Data Bases T3 - DMSN '07 PB - ACM CY - New York, NY, USA SN - 978-159593-911-1 ER - TY - JOUR T1 - Grid Services Base Library: A high-level, procedural application programming interface for writing Globus-based Grid services JF - Future Generation Comp SystFuture Generation Comp Syst Y1 - 2007 A1 - Adam L. Bazinet A1 - Myers, D. S. A1 - Fuetsch, J. A1 - Michael P. Cummings AB - The Grid Services Base Library (GSBL) is a procedural application programming interface (API) that abstracts many of the high-level functions performed by Globus Grid services, thus dramatically lowering the barriers to writing Grid services. The library has been extensively tested and used for computational biology research in a Globus Toolkit-based Grid system, in which no fewer than twenty Grid services written with this API are deployed. VL - 23 ER - TY - JOUR T1 - Hawkeye: an interactive visual analytics tool for genome assemblies JF - Genome BiologyGenome Biology Y1 - 2007 A1 - Schatz, Michael C. A1 - Phillippy, Adam M. A1 - Shneiderman, Ben A1 - Salzberg, Steven L. AB - Genome sequencing remains an inexact science, and genome sequences can contain significant errors if they are not carefully examined. Hawkeye is our new visual analytics tool for genome assemblies, designed to aid in identifying and correcting assembly errors. Users can analyze all levels of an assembly along with summary statistics and assembly metrics, and are guided by a ranking component towards likely mis-assemblies. Hawkeye is freely available and released as part of the open source AMOS project http://amos.sourceforge.net/hawkeye. VL - 8 SN - 1465-6906 ER - TY - JOUR T1 - High-throughput sequence alignment using Graphics Processing Units JF - BMC BioinformaticsBMC Bioinformatics Y1 - 2007 A1 - Schatz, Michael C. A1 - Trapnell, Cole A1 - Delcher, Arthur L. A1 - Varshney, Amitabh VL - 8 SN - 1471-2105 ER - TY - Generic T1 - Knowledge discovery using the sand spatial browser T2 - Proceedings of the 8th annual international conference on Digital government research: bridging disciplines & domains Y1 - 2007 A1 - Samet, Hanan A1 - Phillippy, Adam A1 - Sankaranarayanan, Jagan KW - distance semi-join KW - knowledge discovery KW - sand database system KW - snow cholera map AB - The use of the SAND Internet Browser as a knowledge discovery tool for epidemiological cartography is highlighted by recreating the results of Dr. John Snow's study of the 1854 Cholera epidemic in Soho, London. JA - Proceedings of the 8th annual international conference on Digital government research: bridging disciplines & domains T3 - dg.o '07 PB - Digital Government Society of North America SN - 1-59593-599-1 ER - TY - JOUR T1 - Members of a large retroposon family are determinants of post-transcriptional gene expression in Leishmania. JF - PLoS Pathog Y1 - 2007 A1 - Bringaud, Frederic A1 - Müller, Michaela A1 - Cerqueira, Gustavo Coutinho A1 - Smith, Martin A1 - Rochette, Annie A1 - el-Sayed, Najib M A A1 - Papadopoulou, Barbara A1 - Ghedin, Elodie KW - 3' Untranslated Regions KW - Animals KW - Base Sequence KW - Biological Evolution KW - Down-Regulation KW - Gene Expression Regulation KW - Genome, Protozoan KW - Leishmania KW - Leishmania major KW - Molecular Sequence Data KW - Retroelements KW - RNA, Messenger KW - sequence alignment KW - Trypanosoma brucei brucei KW - Trypanosoma cruzi AB -

Trypanosomatids are unicellular protists that include the human pathogens Leishmania spp. (leishmaniasis), Trypanosoma brucei (sleeping sickness), and Trypanosoma cruzi (Chagas disease). Analysis of their recently completed genomes confirmed the presence of non-long-terminal repeat retrotransposons, also called retroposons. Using the 79-bp signature sequence common to all trypanosomatid retroposons as bait, we identified in the Leishmania major genome two new large families of small elements--LmSIDER1 (785 copies) and LmSIDER2 (1,073 copies)--that fulfill all the characteristics of extinct trypanosomatid retroposons. LmSIDERs are approximately 70 times more abundant in L. major compared to T. brucei and are found almost exclusively within the 3'-untranslated regions (3'UTRs) of L. major mRNAs. We provide experimental evidence that LmSIDER2 act as mRNA instability elements and that LmSIDER2-containing mRNAs are generally expressed at lower levels compared to the non-LmSIDER2 mRNAs. The considerable expansion of LmSIDERs within 3'UTRs in an organism lacking transcriptional control and their role in regulating mRNA stability indicate that Leishmania have probably recycled these short retroposons to globally modulate the expression of a number of genes. To our knowledge, this is the first example in eukaryotes of the domestication and expansion of a family of mobile elements that have evolved to fulfill a critical cellular function.

VL - 3 CP - 9 M3 - 10.1371/journal.ppat.0030136 ER - TY - JOUR T1 - MetaProm: a neural network based meta-predictor for alternative human promoter prediction JF - BMC genomicsBMC Genomics Y1 - 2007 A1 - Wang, J. A1 - Ungar, L. H. A1 - Tseng, H. A1 - Sridhar Hannenhalli PB - BioMed Central Ltd VL - 8 ER - TY - BOOK T1 - Methods in Molecular BiologyComparative GenomicsAnalyzing Patterns of Microbial Evolution Using the Mauve Genome Alignment System Y1 - 2007 A1 - Darling, Aaron E A1 - Todd Treangen A1 - Messeguer, Xavier A1 - Perna, Nicole T ED - Walker, John M. ED - Bergman, Nicholas H. PB - Humana Press CY - Totowa, NJ VL - 396 SN - 978-1-934115-37-4 UR - http://www.springerlink.com/index/10.1007/978-1-59745-515-2http://www.springerlink.com/index/pdf/10.1007/978-1-59745-515-2http://link.springer.com/10.1007/978-1-59745-515-2_10http://www.springerlink.com/index/pdf/10.1007/978-1-59745-515-2_10 M3 - 10.1007/978-1-59745-515-210.1007/978-1-59745-515-2_10 ER - TY - JOUR T1 - Microarray analysis of gene expression induced by sexual contact in Schistosoma mansoni JF - BMC GenomicsBMC Genomics Y1 - 2007 A1 - Waisberg, Michael A1 - Lobo, Francisco A1 - Cerqueira, Gustavo A1 - Passos, Liana A1 - Carvalho, Omar A1 - Franco, Gloria A1 - Najib M. El‐Sayed AB - BACKGROUND:The parasitic trematode Schistosoma mansoni is one of the major causative agents of Schistosomiasis, a disease that affects approximately 200 million people, mostly in developing countries. Since much of the pathology is associated with eggs laid by the female worm, understanding the mechanisms involved in oogenesis and sexual maturation is an important step towards the discovery of new targets for effective drug therapy. It is known that the adult female worm only develops fully in the presence of a male worm and that the rates of oviposition and maturation of eggs are significantly increased by mating. In order to study gene transcripts associated with sexual maturation and oviposition, we compared the gene expression profiles of sexually mature and immature parasites using DNA microarrays.RESULTS:For each experiment, three amplified RNA microarray hybridizations and their dye swaps were analyzed. Our results show that 265 transcripts are differentially expressed in adult females and 53 in adult males when mature and immature worms are compared. Of the genes differentially expressed, 55% are expressed at higher levels in paired females while the remaining 45% are more expressed in unpaired ones and 56.6% are expressed at higher levels in paired male worms while the remaining 43.4% are more expressed in immature parasites. Real-time RT-PCR analysis validated the microarray results. Several new maturation associated transcripts were identified. Genes that were up-regulated in single-sex females were mostly related to energy generation (i.e. carbohydrate and protein metabolism, generation of precursor metabolites and energy, cellular catabolism, and organelle organization and biogenesis) while genes that were down-regulated related to RNA metabolism, reactive oxygen species metabolism, electron transport, organelle organization and biogenesis and protein biosynthesis.CONCLUSION:Our results confirm previous observations related to gene expression induced by sexual maturation in female schistosome worms. They also increase the list of S. mansoni maturation associated transcripts considerably, therefore opening new and exciting avenues for the study of the conjugal biology and development of new drugs against schistosomes. VL - 8 SN - 1471-2164 ER - TY - JOUR T1 - Minimus: a fast, lightweight genome assembler JF - BMC bioinformaticsBMC Bioinformatics Y1 - 2007 A1 - Sommer, D. A1 - Delcher, A. A1 - Salzberg, S. A1 - M. Pop PB - BioMed Central Ltd VL - 8 ER - TY - JOUR T1 - New developments in the InterPro database. JF - Nucleic Acids Res Y1 - 2007 A1 - Mulder, Nicola J A1 - Apweiler, Rolf A1 - Attwood, Teresa K A1 - Bairoch, Amos A1 - Bateman, Alex A1 - Binns, David A1 - Bork, Peer A1 - Buillard, Virginie A1 - Cerutti, Lorenzo A1 - Copley, Richard A1 - Courcelle, Emmanuel A1 - Das, Ujjwal A1 - Daugherty, Louise A1 - Dibley, Mark A1 - Finn, Robert A1 - Fleischmann, Wolfgang A1 - Gough, Julian A1 - Haft, Daniel A1 - Hulo, Nicolas A1 - Hunter, Sarah A1 - Kahn, Daniel A1 - Kanapin, Alexander A1 - Kejariwal, Anish A1 - Labarga, Alberto A1 - Langendijk-Genevaux, Petra S A1 - Lonsdale, David A1 - Lopez, Rodrigo A1 - Letunic, Ivica A1 - Madera, Martin A1 - Maslen, John A1 - McAnulla, Craig A1 - McDowall, Jennifer A1 - Mistry, Jaina A1 - Mitchell, Alex A1 - Nikolskaya, Anastasia N A1 - Orchard, Sandra A1 - Orengo, Christine A1 - Petryszak, Robert A1 - Selengut, Jeremy D A1 - Sigrist, Christian J A A1 - Thomas, Paul D A1 - Valentin, Franck A1 - Wilson, Derek A1 - Wu, Cathy H A1 - Yeats, Corin KW - Databases, Protein KW - Internet KW - Protein Structure, Tertiary KW - Proteins KW - Sequence Analysis, Protein KW - Systems Integration KW - User-Computer Interface AB -

InterPro is an integrated resource for protein families, domains and functional sites, which integrates the following protein signature databases: PROSITE, PRINTS, ProDom, Pfam, SMART, TIGRFAMs, PIRSF, SUPERFAMILY, Gene3D and PANTHER. The latter two new member databases have been integrated since the last publication in this journal. There have been several new developments in InterPro, including an additional reading field, new database links, extensions to the web interface and additional match XML files. InterPro has always provided matches to UniProtKB proteins on the website and in the match XML file on the FTP site. Additional matches to proteins in UniParc (UniProt archive) are now available for download in the new match XML files only. The latest InterPro release (13.0) contains more than 13 000 entries, covering over 78% of all proteins in UniProtKB. The database is available for text- and sequence-based searches via a webserver (http://www.ebi.ac.uk/interpro), and for download by anonymous FTP (ftp://ftp.ebi.ac.uk/pub/databases/interpro). The InterProScan search tool is now also available via a web service at http://www.ebi.ac.uk/Tools/webservices/WSInterProScan.html.

VL - 35 CP - Database issue M3 - 10.1093/nar/gkl841 ER - TY - JOUR T1 - New records of phytoplankton for Bangladesh. 3. Volvocales JF - Bangladesh Journal of Plant TaxonomyBangladesh Journal of Plant Taxonomy Y1 - 2007 A1 - Khondker, Moniruzzaman A1 - Bhuiyan, Rauf Ahmed A1 - Yeasmin, Jenat A1 - Alam, Munirul A1 - Sack, R. Bradley A1 - Huq, Anwar A1 - Rita R. Colwell AB - This study presents 21 species of Chlamydomonas, four species of Carteria, two species of each of Nephroselmis, Pyramidomonas and Scherffelia, and Collodictyon triciliatum, Polytoma minus, Tetrachloridium ? allorgei and Tetraselmis cordiformis. These species have been reported from some ponds of Mathbaria of Pirojpur and Bakerganj of Barisal districts in Bangladesh. VL - 14 SN - 1028-2092 ER - TY - JOUR T1 - New records of phytoplankton for Bangladesh. 4. Chlorococcales JF - Bangladesh Journal of Plant TaxonomyBangladesh Journal of Plant Taxonomy Y1 - 2007 A1 - Khondker, Moniruzzaman A1 - Bhuiyan, Rauf Ahmed A1 - Yeasim, Jenat A1 - Alam, Munirul A1 - Sack, R. Bradley A1 - Huq, Anwar A1 - Rita R. Colwell AB - This study presents three species from each of Schroederia, Monoraphidium and Ankistrodesmus, two species and one variety of Dictyosphaerium, two varieties of Pediastrum, and Tetraedron arthrodesmiforme var. contorta, Chlorotetraedron polymorphum, Myrmecia aquatica, Oocystis tainoensis, Nephrocytium spirale, Kirchneriella irregularis, Coelastrum indicum and Scenedesmus similagineus. These taxa have been reported from some ponds of Mathbaria of Pirojpur and Bakerganj of Barisal Districts in Bangladesh. VL - 14 SN - 1028-2092 ER - TY - JOUR T1 - New Trypanosoma cruzi Repeated Element That Shows Site Specificity for Insertion JF - Eukaryotic CellEukaryotic Cell Y1 - 2007 A1 - Souza, Renata T. A1 - Santos, Marcia R. M. A1 - Lima, Fabio M. A1 - Najib M. El‐Sayed A1 - Myler, Peter J. A1 - Ruiz, Jeronimo C. A1 - da Silveira, Jose Franco AB - A new family of site-specific repeated elements identified in Trypanosoma cruzi, which we named TcTREZO, is described here. TcTREZO appears to be a composite repeated element, since three subregions may be defined within it on the basis of sequence similarities with other T. cruzi sequences. Analysis of the distribution of TcTREZO in the genome clearly indicates that it displays site specificity for insertion. Most TcTREZO elements are flanked by conserved sequences. There is a highly conserved 68-bp sequence at the 5' end of the element and a sequence domain of [~]500 bp without a well-defined borderline at the 3' end. Northern blot hybridization and reverse transcriptase PCR analyses showed that TcTREZO transcripts are expressed as oligo(A)-terminated transcripts whose length corresponds to the unit size of the element (1.6 kb). Transcripts of [~]0.2 kb derived from a small part of TcTREZO are also detected in steady-state RNA. TcTREZO transcripts are unspliced and not translated. The copy number of TcTREZO sequences was estimated to be [~]173 copies per haploid genome. TcTREZO appears to have been assembled by insertions of sequences into a progenitor element. Once associated with each other, these subunits were amplified as a new transposable element. TcTREZO shows site specificity for insertion, suggesting that a sequence-specific endonuclease could be responsible for its insertion at a unique site. VL - 6 ER - TY - Generic T1 - Optimizing mpf queries T2 - Proceedings of the 2007 ACM SIGMOD international conference on Management of data - SIGMOD '07 Y1 - 2007 A1 - Héctor Corrada Bravo A1 - Ramakrishnan, Raghu JA - Proceedings of the 2007 ACM SIGMOD international conference on Management of data - SIGMOD '07 CY - Beijing, China ER - TY - JOUR T1 - Position and distance specificity are important determinants of cis-regulatory motifs in addition to evolutionary conservation JF - Nucleic Acids ResearchNucleic Acids Research Y1 - 2007 A1 - Vardhanabhuti, Saran A1 - Wang, Junwen A1 - Sridhar Hannenhalli AB - Computational discovery of cis-regulatory elements remains challenging. To cope with the high false positives, evolutionary conservation is routinely used. However, conservation is only one of the attributes of cis-regulatory elements and is neither necessary nor sufficient. Here, we assess two additional attributes—positional and inter-motif distance specificity—that are critical for interactions between transcription factors. We first show that for a greater than expected fraction of known motifs, the genes that contain the motifs in their promoters in a position-specific or distance-specific manner are related, both in function and/or in expression pattern. We then use the position and distance specificity to discover novel motifs. Our work highlights the importance of distance and position specificity, in addition to the evolutionary conservation, in discovering cis-regulatory motifs. VL - 35 ER - TY - JOUR T1 - Recovery in culture of viable but nonculturable Vibrio parahaemolyticus: regrowth or resuscitation? JF - The ISME JournalThe ISME journal Y1 - 2007 A1 - Coutard, Fran A1 - ois, A1 - Crassous, Philippe A1 - Droguet, Micka A1 - l, A1 - Gobin, Eric A1 - Rita R. Colwell A1 - Pommepuy, Monique A1 - Hervio-Heath, Dominique KW - ecophysiology KW - ecosystems KW - environmental biotechnology KW - geomicrobiology KW - ISME J KW - microbe interactions KW - microbial communities KW - microbial ecology KW - microbial engineering KW - microbial epidemiology KW - microbial genomics KW - microorganisms AB - The objective of this study was to explore the recovery of culturability of viable but nonculturable (VBNC) Vibrio parahaemolyticus after temperature upshift and to determine whether regrowth or resuscitation occurred. A clinical strain of V. parahaemolyticus Vp5 was rendered VBNC by exposure to artificial seawater (ASW) at 4°C. Aliquots of the ASW suspension of cells (0.1, 1 and 10 ml) were subjected to increased temperatures of 20°C and 37°C. Culturability of the cells in the aliquots was monitored for colony formation on a rich medium and changes in morphology were measured by scanning (SEM) and transmission (TEM) electron microscopy. Samples of VBNC cells were fixed and examined by SEM, revealing a heterogeneous population comprising small cells and larger, flattened cells. Forty-eight hours after temperature upshift to 20°C or 37°C, both elongation and division by binary fission of the cells were observed, employing SEM and TEM, but only in the 10-ml aliquots. The results suggest that a portion of VBNC cells is able to undergo cell division. It is concluded that a portion of VBNC cells of V. parahaemolyticus subjected to cold temperatures remain viable. After temperature upshift, regrowth of those cells, rather than resuscitation of all bacteria of the initial inoculum, appears to be responsible for recovery of culturability of VBNC cells of V. parahaemolyticus. Nutrient in filtrates of VBNC cells is hypothesized to allow growth of the temperature-responsive cells, with cell division occurring via binary fission, but also including an atypical, asymmetric cell division. VL - 1 SN - 1751-7362 N1 - [ccedil]
[euml] ER - TY - JOUR T1 - Schistosoma mansoni genome: Closing in on a final gene set JF - Experimental ParasitologyExperimental Parasitology Y1 - 2007 A1 - Haas, Brian J. A1 - Berriman, Matthew A1 - Hirai, Hirohisa A1 - Cerqueira, Gustavo G. A1 - LoVerde, Philip T. A1 - Najib M. El‐Sayed KW - Annotation KW - Gene finding KW - Genome KW - Schistosoma mansoni AB - The Schistosoma mansoni genome sequencing consortium has recently released the latest versions of the genome assembly as well as an automated preliminary gene structure annotation. The combined datasets constitute a vast resource for researchers to exploit in a variety of post-genomic studies with an emphasis of transcriptomic and proteomic tools. Here we present an innovative method used for combining diverse sources of evidence including ab initio gene predictions, protein and transcript sequence homologies, and cross-genome sequence homologies between S. mansoni and Schistosoma japonicum to define a comprehensive list of protein-coding genes. VL - 117 SN - 0014-4894 ER - TY - JOUR T1 - Spliceosomal small nuclear RNA genes in 11 insect genomes. JF - RNA Y1 - 2007 A1 - Mount, Stephen M A1 - Gotea, Valer A1 - Lin, Chiao-Feng A1 - Hernandez, Kristina A1 - Makalowski, Wojciech KW - Animals KW - Base Sequence KW - Bees KW - Computational Biology KW - Diptera KW - Evolution, Molecular KW - Genes, Insect KW - Genome, Insect KW - Molecular Sequence Data KW - Nucleic Acid Conformation KW - Phylogeny KW - Promoter Regions, Genetic KW - RNA Splicing KW - RNA, Small Nuclear KW - Sequence Analysis, RNA KW - Spliceosomes AB -

The removal of introns from the primary transcripts of protein-coding genes is accomplished by the spliceosome, a large macromolecular complex of which small nuclear RNAs (snRNAs) are crucial components. Following the recent sequencing of the honeybee (Apis mellifera) genome, we used various computational methods, ranging from sequence similarity search to RNA secondary structure prediction, to search for putative snRNA genes (including their promoters) and to examine their pattern of conservation among 11 available insect genomes (A. mellifera, Tribolium castaneum, Bombyx mori, Anopheles gambiae, Aedes aegypti, and six Drosophila species). We identified candidates for all nine spliceosomal snRNA genes in all the analyzed genomes. All the species contain a similar number of snRNA genes, with the exception of A. aegypti, whose genome contains more U1, U2, and U5 genes, and A. mellifera, whose genome contains fewer U2 and U5 genes. We found that snRNA genes are generally more closely related to homologs within the same genus than to those in other genera. Promoter regions for all spliceosomal snRNA genes within each insect species share similar sequence motifs that are likely to correspond to the PSEA (proximal sequence element A), the binding site for snRNA activating protein complex, but these promoter elements vary in sequence among the five insect families surveyed here. In contrast to the other insect species investigated, Dipteran genomes are characterized by a rapid evolution (or loss) of components of the U12 spliceosome and a striking loss of U12-type introns.

VL - 13 CP - 1 M3 - 10.1261/rna.259207 ER - TY - JOUR T1 - SplicePort--an interactive splice-site analysis tool. JF - Nucleic Acids Res Y1 - 2007 A1 - Dogan, Rezarta Islamaj A1 - Getoor, Lise A1 - Wilbur, W John A1 - Mount, Stephen M KW - Base Sequence KW - Chromosome mapping KW - Computational Biology KW - Computer simulation KW - DNA KW - Genome KW - HUMANS KW - Internet KW - Models, Genetic KW - Molecular Sequence Data KW - Pattern Recognition, Automated KW - RNA Splice Sites KW - sequence alignment KW - Sequence Analysis, DNA KW - User-Computer Interface AB -

SplicePort is a web-based tool for splice-site analysis that allows the user to make splice-site predictions for submitted sequences. In addition, the user can also browse the rich catalog of features that underlies these predictions, and which we have found capable of providing high classification accuracy on human splice sites. Feature selection is optimized for human splice sites, but the selected features are likely to be predictive for other mammals as well. With our interactive feature browsing and visualization tool, the user can view and explore subsets of features used in splice-site prediction (either the features that account for the classification of a specific input sequence or the complete collection of features). Selected feature sets can be searched, ranked or displayed easily. The user can group features into clusters and frequency plot WebLogos can be generated for each cluster. The user can browse the identified clusters and their contributing elements, looking for new interesting signals, or can validate previously observed signals. The SplicePort web server can be accessed at http://www.cs.umd.edu/projects/SplicePort and http://www.spliceport.org.

VL - 35 CP - Web Server issue M3 - 10.1093/nar/gkm407 ER - TY - JOUR T1 - SplicePort--An interactive splice-site analysis tool JF - Nucleic Acids ResearchNucleic Acids Research Y1 - 2007 A1 - Dogan, R. I. A1 - Getoor, Lise A1 - Wilbur, W. J. A1 - Stephen M. Mount AB - SplicePort is a web-based tool for splice-site analysis that allows the user to make splice-site predictions for submitted sequences. In addition, the user can also browse the rich catalog of features that underlies these predictions, and which we have found capable of providing high classification accuracy on human splice sites. Feature selection is optimized for human splice sites, but the selected features are likely to be predictive for other mammals as well. With our interactive feature browsing and visualization tool, the user can view and explore subsets of features used in splice-site prediction (either the features that account for the classification of a specific input sequence or the complete collection of features). Selected feature sets can be searched, ranked or displayed easily. The user can group features into clusters and frequency plot WebLogos can be generated for each cluster. The user can browse the identified clusters and their contributing elements, looking for new interesting signals, or can validate previously observed signals. The SplicePort web server can be accessed at http://www.cs.umd.edu/projects/SplicePort and http://www.spliceport.org. VL - 35 SN - 0305-1048, 1362-4962 ER - TY - JOUR T1 - TIGRFAMs and Genome Properties: tools for the assignment of molecular function and biological process in prokaryotic genomes JF - Nucleic acids researchNucleic Acids Research Y1 - 2007 A1 - J. Selengut A1 - Haft, Daniel H. A1 - Davidsen, Tanja A1 - Ganapathy, Anurhada A1 - Gwinn-Giglio, Michelle A1 - Nelson, William C. A1 - Richter, R. Alexander A1 - White, Owen KW - Archaeal Proteins KW - Bacterial Proteins KW - Databases, Protein KW - Genome, Bacterial KW - Genomics KW - Internet KW - Phylogeny KW - software KW - User-Computer Interface AB - TIGRFAMs is a collection of protein family definitions built to aid in high-throughput annotation of specific protein functions. Each family is based on a hidden Markov model (HMM), where both cutoff scores and membership in the seed alignment are chosen so that the HMMs can classify numerous proteins according to their specific molecular functions. Most TIGRFAMs models describe 'equivalog' families, where both orthology and lateral gene transfer may be part of the evolutionary history, but where a single molecular function has been conserved. The Genome Properties system contains a queriable set of metabolic reconstructions, genome metrics and extractions of information from the scientific literature. Its genome-by-genome assertions of whether or not specific structures, pathways or systems are present provide high-level conceptual descriptions of genomic content. These assertions enable comparative genomics, provide a meaningful biological context to aid in manual annotation, support assignments of Gene Ontology (GO) biological process terms and help validate HMM-based predictions of protein function. The Genome Properties system is particularly useful as a generator of phylogenetic profiles, through which new protein family functions may be discovered. The TIGRFAMs and Genome Properties systems can be accessed at http://www.tigr.org/TIGRFAMs and http://www.tigr.org/Genome_Properties. VL - 35 N1 - http://www.ncbi.nlm.nih.gov/pubmed/17151080?dopt=Abstract ER - TY - JOUR T1 - TREMOR—a tool for retrieving transcriptional modules by incorporating motif covariance JF - Nucleic acids researchNucleic Acids Research Y1 - 2007 A1 - Singh, L. N. A1 - Wang, L. S. A1 - Sridhar Hannenhalli PB - Oxford Univ Press VL - 35 ER - TY - JOUR T1 - Ultrastructure of coccoid viable but non‐culturable Vibrio cholerae JF - Environmental MicrobiologyEnvironmental Microbiology Y1 - 2007 A1 - Chaiyanan, Saipin A1 - Chaiyanan, Sitthipan A1 - Grim, Christopher A1 - Maugel, Timothy A1 - Huq, Anwar A1 - Rita R. Colwell AB - Morphology of viable but non-culturable Vibrio cholerae was monitored for 2 years by scanning and transmission electron microscopy. Morphological changes included very small coccoid forms, after extended incubation at 4°C and room temperature, and sequential transformation from curved rods to irregular (∼1 μm) rods to ∼0.8 μm coccoid cells and, ultimately, to tiny coccoid forms (0.07–0.4 μm). Irregular rod-shaped and coccoid cells were equally distributed in microcosms during the first 30–60 days of incubation at both temperatures, but only coccoid cells were observed after incubation for 60 days at 4°C. When V. cholerae O1 and O139, maintained for 30–60 days at both temperatures, were heated to 45°C for 60 s, after serial passage through 0.45 μm and 0.1 μm filters, and plating on Luria–Bertania (LB) agar, only cells larger than 1 μm yielded colonies on LB agar. Approximately 0.1% of heat-treated cultures were culturable. Cell division in the smallest coccoid cells was observed, yielding daughter cells of equal size, whereas other coccoid cells revealed bleb-like, cell wall evagination, followed by transfer of nuclear material. Coccoid cells of V. cholerae O1 and O139 incubated at 4°C for more than 1 year remained substrate responsive and antigenic. VL - 9 SN - 1462-2920 ER - TY - JOUR T1 - A unified model explaining the offsets of overlapping and near-overlapping prokaryotic genes JF - Molecular biology and evolutionMolecular biology and evolution Y1 - 2007 A1 - Kingsford, Carl A1 - Delcher, A. L. A1 - Salzberg, S. L. VL - 24 ER - TY - JOUR T1 - Variola virus topoisomerase: DNA cleavage specificity and distribution of sites in Poxvirus genomes JF - VirologyVirology Y1 - 2007 A1 - Minkah, Nana A1 - Hwang, Young A1 - Perry, Kay A1 - Van Duyne, Gregory D. A1 - Hendrickson, Robert A1 - Lefkowitz, Elliot J. A1 - Sridhar Hannenhalli A1 - Bushman, Frederic D. KW - Annotation of topoisomerase sites KW - Sequence specific recognition KW - Topoisomerase IB KW - Variola virus AB - Topoisomerase enzymes regulate superhelical tension in DNA resulting from transcription, replication, repair, and other molecular transactions. Poxviruses encode an unusual type IB topoisomerase that acts only at conserved DNA sequences containing the core pentanucleotide 5'-(T/C)CCTT-3'. In X-ray structures of the variola virus topoisomerase bound to DNA, protein-DNA contacts were found to extend beyond the core pentanucleotide, indicating that the full recognition site has not yet been fully defined in functional studies. Here we report quantitation of DNA cleavage rates for an optimized 13 bp site and for all possible single base substitutions (40 total sites), with the goals of understanding the molecular mechanism of recognition and mapping topoisomerase sites in poxvirus genome sequences. The data allow a precise definition of enzyme-DNA interactions and the energetic contributions of each. We then used the resulting "action matrix" to show that favorable topoisomerase sites are distributed all along the length of poxvirus DNA sequences, consistent with a requirement for local release of superhelical tension in constrained topological domains. In orthopox genomes, an additional central cluster of sites was also evident. A negative correlation of predicted topoisomerase sites was seen relative to early terminators, but no correlation was seen with early or late promoters. These data define the full variola virus topoisomerase recognition site and provide a new window on topoisomerase function in vivo. VL - 365 SN - 0042-6822 ER - TY - JOUR T1 - Viable but nonculturable Vibrio cholerae O1 in biofilms in the aquatic environment and their role in cholera transmission JF - Proceedings of the National Academy of SciencesProceedings of the National Academy of Sciences Y1 - 2007 A1 - Alam, M. A1 - Sultana, M. A1 - Nair, G. B. A1 - Siddique, A. K. A1 - Hasan, N. A. A1 - Sack, R. B. A1 - Sack, D. A. A1 - Ahmed, K. U. A1 - Sadique, A. A1 - Watanabe, H. A1 - Rita R. Colwell AB - Vibrio cholerae persists in aquatic environments predominantly in a nonculturable state. In this study coccoid, nonculturable V. cholerae O1 in biofilms maintained for 495 days in Mathbaria, Bangladesh, pond water became culturable upon animal passage. Culturability, biofilm formation, and the wbe, ctxA, and rstR2 genes were monitored by culture, direct fluorescent antibody (DFA), and multiplex PCR. DFA counts were not possible after formation of biofilm. Furthermore, wbe, but not ctxA, were amplifiable, even after incubation for 54 and 68 days at room temperature (≈25°C) and 4°C, respectively, when no growth was detectable. Slower biofilm formation and extended culturability were observed for cultures incubated at 4°C, compared with ≈25°C, suggesting biofilm production to be temperature dependent and linked to loss of culturability. Small colonies appearing after incubation in microcosms for 54 and 68 days at 25°C and 4°C, respectively, were wbe positive and ctxA and rstR2 negative, indicating loss of bacteriophage CTXΦ. The coccoid V. cholerae O1 observed as free cells in microcosms incubated for 495 days could not be cultured, but biofilms in the same microcosms yielded culturable cells. It is concluded that biofilms can act as a reservoir for V. cholerae O1 between epidemics because of its long-term viability in biofilms. In contrast to biofilms produced in Mathbaria pond water, V. cholerae O1 in biofilms present in cholera stools and incubated under identical conditions as the Mathbaria pond water biofilms could not be cultured after 2 months, indicating that those V. cholerae cells freshly discharged into the environment are significantly less robust than cells adapted to environmental conditions.Bangladesh bacteriophage CTXΦ DFA multiplex-PCR ctxA VL - 104 SN - 0027-8424, 1091-6490 ER - TY - JOUR T1 - Analysis of fat body transcriptome from the adult tsetse fly, Glossina morsitans morsitans. JF - Insect Mol Biol Y1 - 2006 A1 - Attardo, G M A1 - Strickler-Dinglasan, P A1 - Perkin, S A H A1 - Caler, E A1 - Bonaldo, M F A1 - Soares, M B A1 - El-Sayeed, N A1 - Aksoy, S KW - Adipose Tissue KW - Animals KW - Base Sequence KW - Computational Biology KW - DNA Primers KW - Egg Proteins KW - Expressed Sequence Tags KW - Female KW - Gene Expression Profiling KW - Insect Vectors KW - Male KW - Molecular Sequence Data KW - Reverse Transcriptase Polymerase Chain Reaction KW - Sequence Analysis, DNA KW - Sex Factors KW - Tsetse Flies AB -

Tsetse flies (Diptera: Glossinidia) are vectors of pathogenic African trypanosomes. To develop a foundation for tsetse physiology, a normalized expressed sequence tag (EST) library was constructed from fat body tissue of immune-stimulated Glossina morsitans morsitans. Analysis of 20,257 high-quality ESTs yielded 6372 unique genes comprised of 3059 tentative consensus (TC) sequences and 3313 singletons (available at http://aksoylab.yale.edu). We analysed the putative fat body transcriptome based on homology to other gene products with known functions available in the public domain. In particular, we describe the immune-related products, reproductive function related yolk proteins and milk-gland protein, iron metabolism regulating ferritins and transferrin, and tsetse's major energy source proline biosynthesis. Expression analysis of the three yolk proteins indicates that all are detected in females, while only the yolk protein with similarity to lipases, is expressed in males. Milk gland protein, apparently important for larval nutrition, however, is primarily synthesized by accessory milk gland tissue.

VL - 15 CP - 4 M3 - 10.1111/j.1365-2583.2006.00649.x ER - TY - Generic T1 - A compact mathematical programming formulation for DNA motif finding T2 - Combinatorial Pattern Matching Y1 - 2006 A1 - Kingsford, Carl A1 - Zaslavsky, E. A1 - Singh, M. JA - Combinatorial Pattern Matching ER - TY - JOUR T1 - Comparative genomic evidence for a close relationship between the dimorphic prosthecate bacteria Hyphomonas neptunium and Caulobacter crescentus JF - Journal of bacteriologyJournal of bacteriology Y1 - 2006 A1 - Badger, Jonathan H. A1 - Hoover, Timothy R. A1 - Brun, Yves V. A1 - Weiner, Ronald M. A1 - Laub, Michael T. A1 - Alexandre, Gladys A1 - Mrázek, Jan A1 - Ren, Qinghu A1 - Paulsen, Ian T. A1 - Nelson, Karen E. A1 - Khouri, Hoda M. A1 - Radune, Diana A1 - Sosa, Julia A1 - Dodson, Robert J. A1 - Sullivan, Steven A. A1 - Rosovitz, M. J. A1 - Madupu, Ramana A1 - Brinkac, Lauren M. A1 - Durkin, A. Scott A1 - Daugherty, Sean C. A1 - Kothari, Sagar P. A1 - Giglio, Michelle Gwinn A1 - Zhou, Liwei A1 - Haft, Daniel H. A1 - J. Selengut A1 - Davidsen, Tanja M. A1 - Yang, Qi A1 - Zafar, Nikhat A1 - Ward, Naomi L. KW - Alphaproteobacteria KW - Bacterial Outer Membrane Proteins KW - Caulobacter crescentus KW - cell cycle KW - Chemotaxis KW - DNA, Bacterial KW - Flagella KW - Genome, Bacterial KW - Microbial Viability KW - Molecular Sequence Data KW - Movement KW - Sequence Analysis, DNA KW - Sequence Homology KW - signal transduction AB - The dimorphic prosthecate bacteria (DPB) are alpha-proteobacteria that reproduce in an asymmetric manner rather than by binary fission and are of interest as simple models of development. Prior to this work, the only member of this group for which genome sequence was available was the model freshwater organism Caulobacter crescentus. Here we describe the genome sequence of Hyphomonas neptunium, a marine member of the DPB that differs from C. crescentus in that H. neptunium uses its stalk as a reproductive structure. Genome analysis indicates that this organism shares more genes with C. crescentus than it does with Silicibacter pomeroyi (a closer relative according to 16S rRNA phylogeny), that it relies upon a heterotrophic strategy utilizing a wide range of substrates, that its cell cycle is likely to be regulated in a similar manner to that of C. crescentus, and that the outer membrane complements of H. neptunium and C. crescentus are remarkably similar. H. neptunium swarmer cells are highly motile via a single polar flagellum. With the exception of cheY and cheR, genes required for chemotaxis were absent in the H. neptunium genome. Consistent with this observation, H. neptunium swarmer cells did not respond to any chemotactic stimuli that were tested, which suggests that H. neptunium motility is a random dispersal mechanism for swarmer cells rather than a stimulus-controlled navigation system for locating specific environments. In addition to providing insights into bacterial development, the H. neptunium genome will provide an important resource for the study of other interesting biological processes including chromosome segregation, polar growth, and cell aging. VL - 188 N1 - http://www.ncbi.nlm.nih.gov/pubmed/16980487?dopt=Abstract ER - TY - JOUR T1 - Comparative genomics of emerging human ehrlichiosis agents JF - PLoS geneticsPLoS genetics Y1 - 2006 A1 - Dunning Hotopp, Julie C. A1 - Lin, Mingqun A1 - Madupu, Ramana A1 - Crabtree, Jonathan A1 - Angiuoli, Samuel V. A1 - Eisen, Jonathan A. A1 - Eisen, Jonathan A1 - Seshadri, Rekha A1 - Ren, Qinghu A1 - Wu, Martin A1 - Utterback, Teresa R. A1 - Smith, Shannon A1 - Lewis, Matthew A1 - Khouri, Hoda A1 - Zhang, Chunbin A1 - Niu, Hua A1 - Lin, Quan A1 - Ohashi, Norio A1 - Zhi, Ning A1 - Nelson, William A1 - Brinkac, Lauren M. A1 - Dodson, Robert J. A1 - Rosovitz, M. J. A1 - Sundaram, Jaideep A1 - Daugherty, Sean C. A1 - Davidsen, Tanja A1 - Durkin, Anthony S. A1 - Gwinn, Michelle A1 - Haft, Daniel H. A1 - J. Selengut A1 - Sullivan, Steven A. A1 - Zafar, Nikhat A1 - Zhou, Liwei A1 - Benahmed, Faiza A1 - Forberger, Heather A1 - Halpin, Rebecca A1 - Mulligan, Stephanie A1 - Robinson, Jeffrey A1 - White, Owen A1 - Rikihisa, Yasuko A1 - Tettelin, Hervé KW - Animals KW - Biotin KW - DNA Repair KW - Ehrlichia KW - Ehrlichiosis KW - Genome KW - Genomics KW - HUMANS KW - Models, Biological KW - Phylogeny KW - Rickettsia KW - Ticks AB - Anaplasma (formerly Ehrlichia) phagocytophilum, Ehrlichia chaffeensis, and Neorickettsia (formerly Ehrlichia) sennetsu are intracellular vector-borne pathogens that cause human ehrlichiosis, an emerging infectious disease. We present the complete genome sequences of these organisms along with comparisons to other organisms in the Rickettsiales order. Ehrlichia spp. and Anaplasma spp. display a unique large expansion of immunodominant outer membrane proteins facilitating antigenic variation. All Rickettsiales have a diminished ability to synthesize amino acids compared to their closest free-living relatives. Unlike members of the Rickettsiaceae family, these pathogenic Anaplasmataceae are capable of making all major vitamins, cofactors, and nucleotides, which could confer a beneficial role in the invertebrate vector or the vertebrate host. Further analysis identified proteins potentially involved in vacuole confinement of the Anaplasmataceae, a life cycle involving a hematophagous vector, vertebrate pathogenesis, human pathogenesis, and lack of transovarial transmission. These discoveries provide significant insights into the biology of these obligate intracellular pathogens. VL - 2 N1 - http://www.ncbi.nlm.nih.gov/pubmed/16482227?dopt=Abstract ER - TY - JOUR T1 - Comprehensive analysis of alternative splicing in rice and comparative analyses with Arabidopsis. JF - BMC Genomics Y1 - 2006 A1 - Campbell, Matthew A A1 - Haas, Brian J A1 - Hamilton, John P A1 - Mount, Stephen M A1 - Buell, C Robin KW - Alternative Splicing KW - Arabidopsis KW - DNA, Complementary KW - Expressed Sequence Tags KW - Oryza AB -

BACKGROUND: Recently, genomic sequencing efforts were finished for Oryza sativa (cultivated rice) and Arabidopsis thaliana (Arabidopsis). Additionally, these two plant species have extensive cDNA and expressed sequence tag (EST) libraries. We employed the Program to Assemble Spliced Alignments (PASA) to identify and analyze alternatively spliced isoforms in both species.

RESULTS: A comprehensive analysis of alternative splicing was performed in rice that started with >1.1 million publicly available spliced ESTs and over 30,000 full length cDNAs in conjunction with the newly enhanced PASA software. A parallel analysis was performed with Arabidopsis to compare and ascertain potential differences between monocots and dicots. Alternative splicing is a widespread phenomenon (observed in greater than 30% of the loci with transcript support) and we have described nine alternative splicing variations. While alternative splicing has the potential to create many RNA isoforms from a single locus, the majority of loci generate only two or three isoforms and transcript support indicates that these isoforms are generally not rare events. For the alternate donor (AD) and acceptor (AA) classes, the distance between the splice sites for the majority of events was found to be less than 50 basepairs (bp). In both species, the most frequent distance between AA is 3 bp, consistent with reports in mammalian systems. Conversely, the most frequent distance between AD is 4 bp in both plant species, as previously observed in mouse. Most alternative splicing variations are localized to the protein coding sequence and are predicted to significantly alter the coding sequence.

CONCLUSION: Alternative splicing is widespread in both rice and Arabidopsis and these species share many common features. Interestingly, alternative splicing may play a role beyond creating novel combinations of transcripts that expand the proteome. Many isoforms will presumably have negative consequences for protein structure and function, suggesting that their biological role involves post-transcriptional regulation of gene expression.

VL - 7 M3 - 10.1186/1471-2164-7-327 ER - TY - CHAP T1 - Conservation Patterns in cis-Elements Reveal Compensatory Mutations T2 - Comparative GenomicsComparative Genomics Y1 - 2006 A1 - Evans, Perry A1 - Donahue, Greg A1 - Sridhar Hannenhalli ED - Bourque, Guillaume ED - El-Mabrouk, Nadia AB - Transcriptional regulation critically depends on proper interactions between transcription factors (TF) and their cognate DNA binding sites or cis elements. A better understanding and modelling of the TF-DNA interaction is an important area of research. The Positional Weight Matrix (PWM) is the most common model of TF-DNA binding and it presumes that the nucleotide preferences at individual positions within the binding site are independent. However, studies have shown that this independence assumption does not always hold. If the nucleotide preference at one position depends on the nucleotide at another position, a chance mutation at one position should exert selection pressures at the other position. By comparing the patterns of evolutionary conservation at individual positions within cis elements, here we show that positional dependence within binding sites is highly prevalent. We also show that dependent positions are more likely to be functional, as evidenced by a higher information content and higher conservation. We discuss two examples—Elk-1 and SAP-1 where the inferred compensatory mutation is consistent with known TF-DNA crystal structure. JA - Comparative GenomicsComparative Genomics T3 - Lecture Notes in Computer Science PB - Springer Berlin / Heidelberg VL - 4205 SN - 978-3-540-44529-6 ER - TY - JOUR T1 - Dense Subgraph Computation Via Stochastic Search: Application to Detect Transcriptional Modules JF - BioinformaticsBioinformaticsBioinformaticsBioinformatics Y1 - 2006 A1 - Everett, Logan A1 - Wang, Li-San A1 - Sridhar Hannenhalli AB - Motivation: In a tri-partite biological network of transcription factors, their putative target genes, and the tissues in which the target genes are differentially expressed, a tightly inter-connected (dense) subgraph may reveal knowledge about tissue specific transcription regulation mediated by a specific set of transcription factors—a tissue-specific transcriptional module. This is just one context in which an efficient computation of dense subgraphs in a multi-partite graph is needed.Result: Here we report a generic stochastic search based method to compute dense subgraphs in a graph with an arbitrary number of partitions and an arbitrary connectivity among the partitions. We then use the tool to explore tissue-specific transcriptional regulation in the human genome. We validate our findings in Skeletal muscle based on literature. We could accurately deduce biological processes for transcription factors via the tri-partite clusters of transcription factors, genes, and the functional annotation of genes. Additionally, we propose a few previously unknown TF-pathway associations and tissue-specific roles for certain pathways. Finally, our combined analysis of Cardiac, Skeletal, and Smooth muscle data recapitulates the evolutionary relationship among the three tissues. Contact:sridharh@pcbi.upenn.edu VL - 22 SN - 1367-4803, 1460-2059 ER - TY - CHAP T1 - Detection, Isolation, and Identification of Vibrio cholerae from the Environment T2 - Current Protocols in MicrobiologyCurrent Protocols in Microbiology Y1 - 2006 A1 - Huq, Anwar A1 - Grim, Christopher A1 - Rita R. Colwell A1 - Nair, G. Balakrish KW - culturable KW - DETECTION KW - Environment KW - identification KW - isolation KW - nonculturable KW - viable KW - Vibrio cholerae JA - Current Protocols in MicrobiologyCurrent Protocols in Microbiology PB - John Wiley & Sons, Inc. SN - 9780471729259 ER - TY - JOUR T1 - Differential Transcriptional Response to Nonassociative and Associative Components of Classical Fear Conditioning in the Amygdala and Hippocampus JF - Learning & MemoryLearn. Mem.Learning & MemoryLearn. Mem. Y1 - 2006 A1 - Keeley, Michael B. A1 - Wood, Marcelo A. A1 - Isiegas, Carolina A1 - Stein, Joel A1 - Hellman, Kevin A1 - Sridhar Hannenhalli A1 - Abel, Ted AB - Classical fear conditioning requires the recognition of conditioned stimuli (CS) and the association of the CS with an aversive stimulus. We used Affymetrix oligonucleotide microarrays to characterize changes in gene expression compared to naive mice in both the amygdala and the hippocampus 30 min after classical fear conditioning and 30 min after exposure to the CS in the absence of an aversive stimulus. We found that in the hippocampus, levels of gene regulation induced by classical fear conditioning were not significantly greater than those induced by CS alone, whereas in the amygdala, classical fear conditioning did induce significantly greater levels of gene regulation compared to the CS. Computational studies suggest that transcriptional changes in the hippocampus and amygdala are mediated by large and overlapping but distinct combinations of molecular events. Our results demonstrate that an increase in gene regulation in the amygdala was partially correlated to associative learning and partially correlated to nonassociative components of the task, while gene regulation in the hippocampus was correlated to nonassociative components of classical fear conditioning, including configural learning. VL - 13 SN - 1072-0502, 1549-5485 ER - TY - JOUR T1 - Effect of transport at ambient temperature on detection and isolation of Vibrio cholerae from environmental samples JF - Applied and environmental microbiologyApplied and environmental microbiology Y1 - 2006 A1 - Alam, M. A1 - Sadique, A. A1 - Bhuiyan, N. A. A1 - Nair, G. B. A1 - Siddique, A. K. A1 - Sack, D. A. A1 - Ahsan, S. A1 - Huq, A. A1 - Sack, R. B. A1 - Rita R. Colwell A1 - others, AB - It has long been assumed that prolonged holding of environmental samples at the ambient air temperature prior to bacteriological analysis is detrimental to isolation and detection of Vibrio cholerae, the causative agent of pandemic cholera. The present study was aimed at understanding the effect of transporting environmental samples at the ambient air temperature on isolation and enumeration of V. cholerae. For water and plankton samples held at ambient temperatures ranging from 31°C to 35°C for 20 h, the total counts did not increase significantly but the number of culturable V. cholerae increased significantly compared to samples processed within 1 h of collection, as measured by culture, acridine orange direct count, direct fluorescent-antibody-direct viable count (DFA-DVC), and multiplex PCR analyses. For total coliform counts, total bacterial counts, and DFA-DVC counts, the numbers did not increase significantly, but the culturable plate counts for V. cholerae increased significantly after samples were held at the ambient temperature during transport to the laboratory for analysis. An increase in the recovery of V. cholerae O1 and improved detection of V. cholerae O1 rfb and ctxA also occurred when samples were enriched after they were kept for 20 h at the ambient temperature during transport. Improved detection and isolation of toxigenic V. cholerae from freshwater ecosystems can be achieved by holding samples at the ambient temperature, an observation that has significant implications for tracking this pathogen in diverse aquatic environments. VL - 72 ER - TY - JOUR T1 - Evolution of non-LTR retrotransposons in the trypanosomatid genomes: Leishmania major has lost the active elements JF - Molecular and Biochemical ParasitologyMolecular and Biochemical Parasitology Y1 - 2006 A1 - Bringaud, Frederic A1 - Ghedin, Elodie A1 - Blandin, Gaëlle A1 - Bartholomeu, Daniella C. A1 - Caler, Elisabet A1 - Levin, Mariano J. A1 - Baltz, Théo A1 - Najib M. El‐Sayed KW - Degenerate retroelement KW - Evolution KW - Ingi KW - L1Tc KW - Leishmania major KW - Non-LTR retrotransposon KW - Retroposon KW - Trypanosoma brucei KW - Trypanosoma cruzi AB - The ingi and L1Tc non-LTR retrotransposons - which constitute the ingi clade - are abundant in the genome of the trypanosomatid species Trypanosoma brucei and Trypanosoma cruzi, respectively. The corresponding retroelements, however, are not present in the genome of a closely related trypanosomatid, Leishmania major. To study the evolution of non-LTR retrotransposons in trypanosomatids, we have analyzed all ingi/L1Tc elements and highly degenerate ingi/L1Tc-related sequences identified in the recently completed T. brucei, T. cruzi and L. major genomes. The coding sequences of 242 degenerate ingi/L1Tc-related elements (DIREs) in all three genomes were reconstituted by removing the numerous frame shifts. Three independent phylogenetic analyses conducted on the conserved domains encoded by these elements show that all DIREs, including the 52 L. major DIREs, form a monophyletic group belonging to the ingi clade. This indicates that the trypanosomatid ancestor contained active mobile elements that have been retained in the Trypanosoma species, but were lost from L. major genome, where only remnants (DIRE) are detectable. All 242 DIREs analyzed group together according to their species origin with the exception of 11 T. cruzi DIREs which are close to the T. brucei ingi/DIRE families. Considering the absence of known horizontal transfer between the African T. brucei and the South-American T. cruzi, this suggests that this group of elements evolved at a lower rate when compared to the other trypanosomatid elements. Interestingly, the only nucleotide sequence conserved between ingi and L1Tc (the first 79 residues) is also present at the 5'-extremity of all the full length DIREs and suggests a possible role for this conserved motif, as well as for DIREs. VL - 145 SN - 0166-6851 ER - TY - JOUR T1 - Exopolysaccharide-associated protein sorting in environmental organisms: the PEP-CTERM/EpsH system. Application of a novel phylogenetic profiling heuristic JF - BMC biologyBMC biology Y1 - 2006 A1 - Haft, Daniel H. A1 - Paulsen, Ian T. A1 - Ward, Naomi A1 - J. Selengut KW - Amino Acid Motifs KW - Amino Acid Sequence KW - bacteria KW - Bacterial Proteins KW - Biofilms KW - Genome, Bacterial KW - Markov chains KW - Molecular Sequence Data KW - Phylogeny KW - Polysaccharides, Bacterial KW - Protein Sorting Signals KW - Protein Transport KW - Seawater KW - sequence alignment KW - Soil Microbiology AB - BACKGROUND: Protein translocation to the proper cellular destination may be guided by various classes of sorting signals recognizable in the primary sequence. Detection in some genomes, but not others, may reveal sorting system components by comparison of the phylogenetic profile of the class of sorting signal to that of various protein families. RESULTS: We describe a short C-terminal homology domain, sporadically distributed in bacteria, with several key characteristics of protein sorting signals. The domain includes a near-invariant motif Pro-Glu-Pro (PEP). This possible recognition or processing site is followed by a predicted transmembrane helix and a cluster rich in basic amino acids. We designate this domain PEP-CTERM. It tends to occur multiple times in a genome if it occurs at all, with a median count of eight instances; Verrucomicrobium spinosum has sixty-five. PEP-CTERM-containing proteins generally contain an N-terminal signal peptide and exhibit high diversity and little homology to known proteins. All bacteria with PEP-CTERM have both an outer membrane and exopolysaccharide (EPS) production genes. By a simple heuristic for screening phylogenetic profiles in the absence of pre-formed protein families, we discovered that a homolog of the membrane protein EpsH (exopolysaccharide locus protein H) occurs in a species when PEP-CTERM domains are found. The EpsH family contains invariant residues consistent with a transpeptidase function. Most PEP-CTERM proteins are encoded by single-gene operons preceded by large intergenic regions. In the Proteobacteria, most of these upstream regions share a DNA sequence, a probable cis-regulatory site that contains a sigma-54 binding motif. The phylogenetic profile for this DNA sequence exactly matches that of three proteins: a sigma-54-interacting response regulator (PrsR), a transmembrane histidine kinase (PrsK), and a TPR protein (PrsT). CONCLUSION: These findings are consistent with the hypothesis that PEP-CTERM and EpsH form a protein export sorting system, analogous to the LPXTG/sortase system of Gram-positive bacteria, and correlated to EPS expression. It occurs preferentially in bacteria from sediments, soils, and biofilms. The novel method that led to these findings, partial phylogenetic profiling, requires neither global sequence clustering nor arbitrary similarity cutoffs and appears to be a rapid, effective alternative to other profiling methods. VL - 4 N1 - http://www.ncbi.nlm.nih.gov/pubmed/16930487?dopt=Abstract ER - TY - JOUR T1 - Functional Analysis of Hes-1 in Preadipocytes JF - Molecular EndocrinologyMolecular EndocrinologyMolecular EndocrinologyMolecular Endocrinology Y1 - 2006 A1 - Ross, David A. A1 - Sridhar Hannenhalli A1 - Tobias, John W. A1 - Cooch, Neil A1 - Shiekhattar, Ramin A1 - Kadesch, Tom AB - Notch signaling blocks differentiation of 3T3-L1 preadipocytes, and this can be mimicked by constitutive expression of the Notch target gene Hes-1. Although considered initially to function only as a repressor, recent evidence indicates that Hes-1 can also activate transcription. We show here that the domains of Hes-1 needed to block adipogenesis coincide with those necessary for transcriptional repression. HRT1, another basic-helix-loop-helix protein and potential Hes-1 partner, was also induced by Notch in 3T3-L1 cells but did not block adipogenesis, suggesting that Hes-1 functions primarily as a homodimer or possibly as a heterodimer with an unknown partner. Purification of Hes-1 identified the Groucho/transducin-like enhancer of split family of corepressors as the only significant Hes-1 interacting proteins in vivo. An evaluation of global gene expression in preadipocytes identified approximately 200 Hes-1-responsive genes comprising roughly equal numbers of up-regulated and down-regulated genes. However, promoter analyses indicated that the down-regulated genes were significantly more likely to contain Hes-1 binding sites, indicating that Hes-1 is more likely to repress transcription of its direct targets. We conclude that Notch most likely blocks adipogenesis through the induction of Hes-1 homodimers, which repress transcription of key target genes. VL - 20 SN - 0888-8809, 1944-9917 ER - TY - Generic T1 - How A.I. and multi-robot systems research will accelerate our understanding of social animal behavior Y1 - 2006 A1 - Tucker Balch A1 - Frank Dellaert A1 - Adam Feldman A1 - Andrew Guillory A1 - Charles Isbell A1 - Zia Khan A1 - Andrew Stein A1 - Hank Wilde JA - Proceedings of the IEEE VL - 94 CP - 7 ER - TY - Generic T1 - How Multirobot Systems Research will Accelerate our Understanding of Social Animal Behavior Y1 - 2006 A1 - Balch, T. A1 - Dellaert, F. A1 - Feldman, A. A1 - Guillory, A. A1 - Isbell, C.L. A1 - Khan, Z. A1 - Pratt, S.C. A1 - Stein, A.N. A1 - Wilde, H. JA - Proceedings of the IEEE VL - 94 UR - http://ieeexplore.ieee.org/lpdocs/epic03/wrapper.htm?arnumber=1677955 CP - 7 J1 - Proc. IEEE M3 - 10.1109/JPROC.2006.876969 ER - TY - JOUR T1 - Identification and cross-species comparison of canine osteoarthritic gene regulatory cis-elements JF - Osteoarthritis and cartilage/OARS, Osteoarthritis Research SocietyOsteoarthritis and cartilage/OARS, Osteoarthritis Research Society Y1 - 2006 A1 - Sridhar Hannenhalli A1 - Middleton, R. P. A1 - Levy, S. A1 - Perroud, B. A1 - Holzwarth, J. A. A1 - McDonald, K. A1 - Hannah, S. S. A1 - others, VL - 14 ER - TY - JOUR T1 - An interaction-dependent model for transcription factor binding JF - Systems Biology and Regulatory GenomicsSystems Biology and Regulatory Genomics Y1 - 2006 A1 - Wang, L. S. A1 - Jensen, S. A1 - Sridhar Hannenhalli PB - Springer ER - TY - JOUR T1 - Invited Talk: Deciphering Gene Regulatory Networks by in silico approaches JF - 6th International Workshop on Data Mining in Bioinformatics (BIOKDD06)6th International Workshop on Data Mining in Bioinformatics (BIOKDD06) Y1 - 2006 A1 - Sridhar Hannenhalli AB - Biological processes are controlled at various levels in the celland while these mechanisms are poorly understood, tran- scriptional control is widely recognized as an important com- ponent and a better understanding of which will provide an efficient means for the therapeutic intervention in disease processes. We have been focusing on various computational problems pertaining to transcriptional regulation, namely, (1) representation and identification of transcription factor binding sites,(2) PolII promoter prediction,(3) Predicting interaction among transcription factors,(4) Transcriptional modeling, ie identifying arrangements of TFs that co- regulate a set of transcripts. I will present a brief overview of the computational approaches and challenges as well as a number of applications including transcriptional regulation in memory storage, heart failure, and osteoarthritis. ER - TY - JOUR T1 - A mammalian promoter model links cis elements to genetic networks JF - Biochemical and Biophysical Research CommunicationsBiochemical and Biophysical Research Communications Y1 - 2006 A1 - Wang, Junwen A1 - Sridhar Hannenhalli KW - conservation KW - Core promoter prediction KW - CpG island KW - Genetic networks KW - Position-specific motif KW - Propensity KW - Transcription factor binding site (TFBS) AB - An accurate identification of gene promoters remains an important challenge. Computational approaches for this problem rely on promoter sequence attributes that are believed to be critical for transcription initiation. Here we report a probabilistic model that captures two important properties of promoters, not used by previous methods, viz., the location preference and co-occurrence of promoter elements. Additionally, we found that many of the position-specific DNA elements are strongly linked with the function of the gene product. For instance, a highly conserved motif CCTTT at -1 position is strongly associated with protein synthesis, cellular and tissue development. Our comparative analysis of promoter classes reveals that the promoters devoid of CpG islands are more conserved and have fewer alternative transcription start sites. The discovered links between promoter elements and gene function allows us to infer genetic networks from promoter elements. The web server for the PSPA promoter predictor is available at http://cagr.pcbi.upenn.edu/PSPA. VL - 347 SN - 0006-291X ER - TY - JOUR T1 - MCMC Data Association and Sparse Factorization Updating for Real Time Multitarget Tracking with Merged and Multiple Measurements JF - IEEE Transactions on Pattern Analysis and Machine Intelligence Y1 - 2006 A1 - Zia Khan A1 - Tucker Balch A1 - Frank Dellaert VL - 28 CP - 12 ER - TY - Generic T1 - MCMC data association and sparse factorization updating for real time multitarget tracking with merged and multiple measurements. Y1 - 2006 A1 - Khan, Zia A1 - Balch, Tucker A1 - Dellaert, Frank KW - algorithms KW - Artificial Intelligence KW - Image Enhancement KW - Image Interpretation, Computer-Assisted KW - Information Storage and Retrieval KW - Movement KW - Pattern Recognition, Automated KW - Reproducibility of Results KW - Sensitivity and Specificity KW - Subtraction Technique AB -

In several multitarget tracking applications, a target may return more than one measurement per target and interacting targets may return multiple merged measurements between targets. Existing algorithms for tracking and data association, initially applied to radar tracking, do not adequately address these types of measurements. Here, we introduce a probabilistic model for interacting targets that addresses both types of measurements simultaneously. We provide an algorithm for approximate inference in this model using a Markov chain Monte Carlo (MCMC)-based auxiliary variable particle filter. We Rao-Blackwellize the Markov chain to eliminate sampling over the continuous state space of the targets. A major contribution of this work is the use of sparse least squares updating and downdating techniques, which significantly reduce the computational cost per iteration of the Markov chain. Also, when combined with a simple heuristic, they enable the algorithm to correctly focus computation on interacting targets. We include experimental results on a challenging simulation sequence. We test the accuracy of the algorithm using two sensor modalities, video, and laser range data. We also show the algorithm exhibits real time performance on a conventional PC.

JA - IEEE Trans Pattern Anal Mach Intell VL - 28 CP - 12 M3 - 10.1109/TPAMI.2006.247 ER - TY - JOUR T1 - Metagenomic Analysis of the Human Distal Gut Microbiome JF - ScienceScienceScienceScience Y1 - 2006 A1 - Gill, Steven R. A1 - M. Pop A1 - DeBoy, Robert T. A1 - Eckburg, Paul B. A1 - Turnbaugh, Peter J. A1 - Samuel, Buck S. A1 - Gordon, Jeffrey I. A1 - Relman, David A. A1 - Fraser-Liggett, Claire M. A1 - Nelson, Karen E. AB - The human intestinal microbiota is composed of 1013 to 1014 microorganisms whose collective genome (“microbiome”) contains at least 100 times as many genes as our own genome. We analyzed ∼78 million base pairs of unique DNA sequence and 2062 polymerase chain reaction–amplified 16S ribosomal DNA sequences obtained from the fecal DNAs of two healthy adults. Using metabolic function analyses of identified genes, we compared our human genome with the average content of previously sequenced microbial genomes. Our microbiome has significantly enriched metabolism of glycans, amino acids, and xenobiotics; methanogenesis; and 2-methyl-d-erythritol 4-phosphate pathway–mediated biosynthesis of vitamins and isoprenoids. Thus, humans are superorganisms whose metabolism represents an amalgamation of microbial and human attributes. VL - 312 SN - 0036-8075, 1095-9203 ER - TY - JOUR T1 - M-GCAT: interactively and efficiently constructing large-scale multiple genome comparison frameworks in closely related species JF - BMC bioinformatics Y1 - 2006 A1 - Todd Treangen A1 - Messeguer, Xavier VL - 7 ER - TY - Generic T1 - Microbial diversity in the era of genomics T2 - SYMPOSIA-SOCIETY FOR GENERAL MICROBIOLOGY Y1 - 2006 A1 - Rita R. Colwell JA - SYMPOSIA-SOCIETY FOR GENERAL MICROBIOLOGY VL - 66 ER - TY - JOUR T1 - Molecular Characterization of Serine-, Alanine-, and Proline-Rich Proteins of Trypanosoma cruzi and Their Possible Role in Host Cell Infection JF - Infect. Immun.Infect. Immun. Y1 - 2006 A1 - Baida, Renata C. P. A1 - Santos, Marcia R. M. A1 - Carmo, Mirian S. A1 - Yoshida, Nobuko A1 - Ferreira, Danielle A1 - Ferreira, Alice Teixeira A1 - El Sayed, Najib M. A1 - Andersson, Björn A1 - da Silveira, Jose Franco AB - We previously reported the isolation of a novel protein gene family, termed SAP (serine-, alanine-, and proline-rich protein), from Trypanosoma cruzi. Aided by the availability of the completed genome sequence of T. cruzi, we have now identified 39 full-length sequences of SAP, six pseudogenes and four partial genes. SAPs share a central domain of about 55 amino acids and can be divided into four groups based on their amino (N)- and carboxy (C)-terminal sequences. Some SAPs have conserved N- and C-terminal domains encoding a signal peptide and a glycosylphosphatidylinositol anchor addition site, respectively. Analysis of the expression of SAPs in metacyclic trypomastigotes by two-dimensional electrophoresis and immunoblotting revealed that they are likely to be posttranslationally modified in vivo. We have also demonstrated that some SAPs are shed into the extracellular medium. The recombinant SAP exhibited an adhesive capacity toward mammalian cells, where binding was dose dependent and saturable, indicating a possible ligand-receptor interaction. SAP triggered the host cell Ca2+ response required for parasite internalization. A cell invasion assay performed in the presence of SAP showed inhibition of internalization of the metacyclic forms of the CL strain. Taken together, these results show that SAP is involved in the invasion of mammalian cells by metacyclic trypomastigotes, and they confirm the hypothesis that infective trypomastigotes exploit an arsenal of surface glycoproteins and shed proteins to induce signaling events required for their internalization. VL - 74 ER - TY - CONF T1 - Multitarget Tracking with Split and Merged Measurements T2 - 2005 IEEE Computer Society Conference on Computer Vision and Pattern Recognition (CVPR'05)2005 IEEE Computer Society Conference on Computer Vision and Pattern Recognition (CVPR'05) Y1 - 2006 A1 - Khan, Z. A1 - Balch, T. A1 - Dellaert, F. JA - 2005 IEEE Computer Society Conference on Computer Vision and Pattern Recognition (CVPR'05)2005 IEEE Computer Society Conference on Computer Vision and Pattern Recognition (CVPR'05) PB - IEEE CY - San Diego, CA, USA UR - http://ieeexplore.ieee.org/lpdocs/epic03/wrapper.htm?arnumber=1467323 M3 - 10.1109/CVPR.2005.245 ER - TY - BOOK T1 - Oceans And Health: Pathogens In The Marine Environment Y1 - 2006 A1 - Belkin, Shimshon A1 - Rita R. Colwell KW - Electronic books KW - Marine microbiology KW - Medical / Epidemiology KW - Medical / Microbiology KW - Nature / Animals / Marine Life KW - Pathogenic microorganisms KW - Science / Environmental Science KW - Science / Life Sciences / Biology KW - Science / Life Sciences / Marine Biology KW - Science / Life Sciences / Microbiology KW - Seawater/ microbiology AB - The release of non-disinfected wastewaters into the marine environment is a common worldwide practice, in under-developed as well as in highly developed countries. Consequently, the seas are constantly infused with wastewater bacteria, among them highly pathogenic ones. In view of the public health significance of this phenomenon, it is surprising how little is actually known concerning the fate of such bacteria once they enter the sea. While numerous studies have addressed the effects of various environmental parameters on colony formation, many of them actually ignore the fact that bacteria can retain viability and infectivity while losing colony-forming ability. Only in recent years have efforts also been directed at unraveling the mechanisms determining bacterial sensitivity or survival under these conditions. This, therefore, is one subject of Oceans and Health: Pathogens in the Marine Environment: the survival, infectivity, pathogenicity and viability of enteric bacteria in the sea. Chapters also detail the public health aspects of wastewater release, civil engineering and economic considerations, other sources of pathogens, and much more. PB - Springer SN - 9780387237084 ER - TY - JOUR T1 - An optimized system for expression and purification of secreted bacterial proteins JF - Protein Expression and PurificationProtein Expression and Purification Y1 - 2006 A1 - Geisbrecht, Brian V. A1 - Bouyain, Samuel A1 - M. Pop KW - Pathogens KW - Secreted proteins KW - Toxins KW - Virulence factors AB - In this report, we describe an optimized system for the efficient overexpression, purification, and refolding of secreted bacterial proteins. Candidate secreted proteins were produced recombinantly in Escherichia coli as Tobacco Etch Virus protease-cleavable hexahistidine-c-myc eptiope fusion proteins. Without regard to their initial solubility, recombinant fusion proteins were extracted from whole cells with guanidium chloride, purified under denaturing conditions by immobilized metal affinity chromatography, and refolded by rapid dilution into a solution containing only Tris buffer and sodium chloride. Following concentration on the same resin under native conditions, each protein was eluted for further purification and/or characterization. Preliminary studies on a test set of 12 secreted proteins ranging in size from 13 to 130 kDa yielded between 10 and 50 mg of fusion protein per liter of induced culture at greater than 90% purity, as judged by Coomassie-stained SDS–PAGE. Of the nine proteins further purified, analytical gel filtration chromatography indicated that each was a monomer in solution and circular dichroism spectroscopy revealed that each had adopted a well-defined secondary structure. While there are many potential applications for this system, the results presented here suggest that it will be particularly useful for investigators employing structural approaches to understand protein function, as attested to by the crystal structures of three proteins purified using this methodology (B.V. Geisbrecht, B.Y. Hamaoka, B. Perman, A. Zemla, D.J. Leahy, J. Biol. Chem. 280 (2005) 17243–17250). VL - 46 SN - 1046-5928 ER - TY - JOUR T1 - Patterns of sequence conservation in presynaptic neural genes JF - Genome BiolGenome Biol Y1 - 2006 A1 - Hadley, D. A1 - Murphy, T. A1 - Valladares, O. A1 - Sridhar Hannenhalli A1 - Ungar, L. A1 - Kim, J. A1 - Bucan, M. A1 - others, VL - 7 ER - TY - BOOK T1 - Procrastination Leads to Efficient Filtration for Local Multiple Alignment Y1 - 2006 A1 - Darling, Aaron E. A1 - Todd Treangen A1 - Zhang, Louxin A1 - Kuiken, Carla A1 - Messeguer, Xavier A1 - Perna, Nicole T. PB - Springer Berlin Heidelberg CY - Berlin, Heidelberg VL - 4175 SN - 978-3-540-39583-6 UR - http://www.springerlink.com/index/10.1007/11851561http://www.springerlink.com/index/pdf/10.1007/11851561http://link.springer.com/10.1007/11851561_12http://www.springerlink.com/index/pdf/10.1007/11851561_12 M3 - 10.1007/1185156110.1007/11851561_12 ER - TY - CONF T1 - Procrastination leads to efficient filtration for local multiple alignment T2 - International Workshop on Algorithms in Bioinformatics Y1 - 2006 A1 - Darling, Aaron E A1 - Todd Treangen A1 - Zhang, Louxin A1 - Kuiken, Carla A1 - Messeguer, Xavier A1 - Perna, Nicole T JA - International Workshop on Algorithms in Bioinformatics PB - Springer Berlin Heidelberg ER - TY - JOUR T1 - Recurring genomic breaks in independent lineages support genomic fragility JF - BMC Evolutionary BiologyBMC Evolutionary Biology Y1 - 2006 A1 - Hinsch, Hanno A1 - Sridhar Hannenhalli AB - Recent findings indicate that evolutionary breaks in the genome are not randomly distributed, and that certain regions, so-called fragile regions, are predisposed to breakages. Previous approaches to the study of genomic fragility have examined the distribution of breaks, as well as the coincidence of breaks with segmental duplications and repeats, within a single species. In contrast, we investigate whether this regional fragility is an inherent genomic characteristic and is thus conserved over multiple independent lineages. VL - 6 SN - 1471-2148 ER - TY - JOUR T1 - Retroviral DNA integration: viral and cellular determinants of target-site selection JF - PLoS pathogensPLoS pathogens Y1 - 2006 A1 - Lewinski, M. K. A1 - Yamashita, M. A1 - Emerman, M. A1 - Ciuffi, A. A1 - Marshall, H. A1 - Crawford, G. A1 - Collins, F. A1 - Shinn, P. A1 - Leipzig, J. A1 - Sridhar Hannenhalli A1 - others, PB - Public Library of Science VL - 2 ER - TY - JOUR T1 - Schistosoma mansoni (Platyhelminthes, Trematoda) nuclear receptors: Sixteen new members and a novel subfamily JF - GeneGene Y1 - 2006 A1 - Wu, Wenjie A1 - Niles, Edward G. A1 - Najib M. El‐Sayed A1 - Berriman, Matthew A1 - LoVerde, Philip T. KW - Nuclear receptors KW - Schistosoma mansoni AB - Nuclear receptors (NRs) are important transcriptional modulators in metazoans. Sixteen new NRs were identified in the Platyhelminth trematode, Schistosoma mansoni. Three were found to possess novel tandem DNA-binding domains that identify a new subfamily of NR. Two NRs are homologues of the thyroid hormone receptor that previously were thought to be restricted to chordates. This study brings the total number of identified NR in S. mansoni to 21. Phylogenetic and comparative genomic analyses demonstrate that S. mansoni NRs share an evolutionary lineage with that of arthropods and vertebrates. Phylogenic analysis shows that more than half of the S. mansoni nuclear receptors evolved from a second gene duplication. As the second gene duplication of NRs was thought to be specific to vertebrates, our data challenge the current theory of NR evolution. VL - 366 SN - 0378-1119 ER - TY - JOUR T1 - Seasonal Cholera Caused by Vibrio Cholerae Serogroups O1 and O139 in the Coastal Aquatic Environment of Bangladesh JF - Applied and Environmental MicrobiologyAppl. Environ. Microbiol.Applied and Environmental MicrobiologyAppl. Environ. Microbiol. Y1 - 2006 A1 - Alam, Munirul A1 - Hasan, Nur A. A1 - Sadique, Abdus A1 - Bhuiyan, N. A. A1 - Ahmed, Kabir U. A1 - Nusrin, Suraia A1 - Nair, G. Balakrish A1 - Siddique, A. K. A1 - Sack, R. Bradley A1 - Sack, David A. A1 - Huq, Anwar A1 - Rita R. Colwell AB - Since Vibrio cholerae O139 first appeared in 1992, both O1 El Tor and O139 have been recognized as the epidemic serogroups, although their geographic distribution, endemicity, and reservoir are not fully understood. To address this lack of information, a study of the epidemiology and ecology of V. cholerae O1 and O139 was carried out in two coastal areas, Bakerganj and Mathbaria, Bangladesh, where cholera occurs seasonally. The results of a biweekly clinical study (January 2004 to May 2005), employing culture methods, and of an ecological study (monthly in Bakerganj and biweekly in Mathbaria from March 2004 to May 2005), employing direct and enrichment culture, colony blot hybridization, and direct fluorescent-antibody methods, showed that cholera is endemic in both Bakerganj and Mathbaria and that V. cholerae O1, O139, and non-O1/non-O139 are autochthonous to the aquatic environment. Although V. cholerae O1 and O139 were isolated from both areas, most noteworthy was the isolation of V. cholerae O139 in March, July, and September 2004 in Mathbaria, where seasonal cholera was clinically linked only to V. cholerae O1. In Mathbaria, V. cholerae O139 emerged as the sole cause of a significant outbreak of cholera in March 2005. V. cholerae O1 reemerged clinically in April 2005 and established dominance over V. cholerae O139, continuing to cause cholera in Mathbaria. In conclusion, the epidemic potential and coastal aquatic reservoir for V. cholerae O139 have been demonstrated. Based on the results of this study, the coastal ecosystem of the Bay of Bengal is concluded to be a significant reservoir for the epidemic serogroups of V. cholerae. VL - 72 SN - 0099-2240, 1098-5336 ER - TY - JOUR T1 - Selection of Target Sites for Mobile DNA Integration in the Human Genome JF - PLoS Comput BiolPLoS Comput BiolPLoS Comput BiolPLoS Comput Biol Y1 - 2006 A1 - Berry, Charles A1 - Sridhar Hannenhalli A1 - Leipzig, Jeremy A1 - Bushman, Frederic D. AB - DNA sequences from retroviruses, retrotransposons, DNA transposons, and parvoviruses can all become integrated into the human genome. Accumulation of such sequences accounts for at least 40% of our genome today. These integrating elements are also of interest as gene-delivery vectors for human gene therapy. Here we present a comprehensive bioinformatic analysis of integration targeting by HIV, MLV, ASLV, SFV, L1, SB, and AAV. We used a mathematical method which allowed annotation of each base pair in the human genome for its likelihood of hosting an integration event by each type of element, taking advantage of more than 200 types of genomic annotation. This bioinformatic resource documents a wealth of new associations between genomic features and integration targeting. The study also revealed that the length of genomic intervals analyzed strongly affected the conclusions drawn—thus, answering the question “What genomic features affect integration?” requires carefully specifying the length scale of interest. VL - 2 ER - TY - JOUR T1 - Septaplex PCR assay for rapid identification of Vibrio cholerae including detection of virulence and int SXT genes JF - FEMS Microbiology LettersFEMS Microbiology Letters Y1 - 2006 A1 - Mantri, Chinmay K. A1 - Mohapatra, Saswat S. A1 - Ramamurthy, Thandavarayan A1 - Ghosh, Raikamal A1 - Rita R. Colwell A1 - Singh, Durg V. KW - DETECTION KW - intsxt KW - septaplex PCR KW - Vibrio cholerae KW - virulence AB - In this study, we describe a septaplex PCR assay for rapid identification of Vibrio cholerae including detection of the virulence and intsxt genes. Conditions were optimized to amplify fragments of ISRrRNA (encoding for 16S–23S rRNA gene, Intergenic spacer regions), O1rfb (O1 serogroup specific rfb), O139rfb (O139 serogroup specific rfb), ctxA (cholera toxin subunit A), tcpA (toxin coregulated pilus), and intsxt (sxt integron) simultaneously in a single PCR. The septaplex PCR was evaluated using 211 strains of V. cholerae and six water samples for in situ testing. PCR results were correlated with genotype data obtained by individual PCR and slot-blot assays. The one-step PCR described here can be used to identify V. cholerae accurately and rapidly. Also, the virulence and intsxt genes can be simultaneously detected, providing a useful method for monitoring pathogenic, intsxt-positive and nonpathogenic, intsxt-negative V. cholerae serogroups both in the environment and clinical settings. VL - 265 SN - 1574-6968 ER - TY - JOUR T1 - Toxigenic Vibrio Cholerae in the Aquatic Environment of Mathbaria, Bangladesh JF - Applied and Environmental MicrobiologyAppl. Environ. Microbiol.Applied and Environmental MicrobiologyAppl. Environ. Microbiol. Y1 - 2006 A1 - Alam, Munirul A1 - Sultana, Marzia A1 - Nair, G. Balakrish A1 - Sack, R. Bradley A1 - Sack, David A. A1 - Siddique, A. K. A1 - Ali, Afsar A1 - Huq, Anwar A1 - Rita R. Colwell AB - Toxigenic Vibrio cholerae, rarely isolated from the aquatic environment between cholera epidemics, can be detected in what is now understood to be a dormant stage, i.e., viable but nonculturable when standard bacteriological methods are used. In the research reported here, biofilms have proved to be a source of culturable V. cholerae, even in nonepidemic periods. Biweekly environmental surveillance for V. cholerae was carried out in Mathbaria, an area of cholera endemicity adjacent to the Bay of Bengal, with the focus on V. cholerae O1 and O139 Bengal. A total of 297 samples of water, phytoplankton, and zooplankton were collected between March and December 2004, yielding eight V. cholerae O1 and four O139 Bengal isolates. A combination of culture methods, multiplex-PCR, and direct fluorescent antibody (DFA) counting revealed the Mathbaria aquatic environment to be a reservoir for V. cholerae O1 and O139 Bengal. DFA results showed significant clumping of the bacteria during the interepidemic period for cholera, and the fluorescent micrographs revealed large numbers of V. cholerae O1 in thin films of exopolysaccharides (biofilm). A similar clumping of V. cholerae O1 was also observed in samples collected from Matlab, Bangladesh, where cholera also is endemic. Thus, the results of the study provided in situ evidence for V. cholerae O1 and O139 in the aquatic environment, predominantly as viable but nonculturable cells and culturable cells in biofilm consortia. The biofilm community is concluded to be an additional reservoir of cholera bacteria in the aquatic environment between seasonal epidemics of cholera in Bangladesh. VL - 72 SN - 0099-2240, 1098-5336 ER - TY - JOUR T1 - Transcriptional Genomics Associates FOX Transcription Factors With Human Heart Failure JF - CirculationCirculation Y1 - 2006 A1 - Sridhar Hannenhalli A1 - Putt, Mary E. A1 - Gilmore, Joan M. A1 - Wang, Junwen A1 - Parmacek, Michael S. A1 - Epstein, Jonathan A. A1 - Morrisey, Edward E. A1 - Margulies, Kenneth B. A1 - Cappola, Thomas P. AB - Background— Specific transcription factors (TFs) modulate cardiac gene expression in murine models of heart failure, but their relevance in human subjects remains untested. We developed and applied a computational approach called transcriptional genomics to test the hypothesis that a discrete set of cardiac TFs is associated with human heart failure.Methods and Results— RNA isolates from failing (n=196) and nonfailing (n=16) human hearts were hybridized with Affymetrix HU133A arrays, and differentially expressed heart failure genes were determined. TF binding sites overrepresented in the −5-kb promoter sequences of these heart failure genes were then determined with the use of public genome sequence databases. Binding sites for TFs identified in murine heart failure models (MEF2, NKX, NF-AT, and GATA) were significantly overrepresented in promoters of human heart failure genes (P<0.002; false discovery rate 2% to 4%). In addition, binding sites for FOX TFs showed substantial overrepresentation in both advanced human and early murine heart failure (P<0.002 and false discovery rate <4% for each). A role for FOX TFs was supported further by expression of FOXC1, C2, P1, P4, and O1A in failing human cardiac myocytes at levels similar to established hypertrophic TFs and by abundant FOXP1 protein in failing human cardiac myocyte nuclei.Conclusions— Our results provide the first evidence that specific TFs identified in murine models (MEF2, NKX, NFAT, and GATA) are associated with human heart failure. Moreover, these data implicate specific members of the FOX family of TFs (FOXC1, C2, P1, P4, and O1A) not previously suggested in heart failure pathogenesis. These findings provide a crucial link between animal models and human disease and suggest a specific role for FOX signaling in modulating the hypertrophic response of the heart to stress in humans. VL - 114 ER - TY - JOUR T1 - The Trypanosoma cruzi L1Tc and NARTc non-LTR retrotransposons show relative site specificity for insertion JF - Molecular biology and evolutionMolecular biology and evolution Y1 - 2006 A1 - Bringaud, F. A1 - Bartholomeu, D. C. A1 - Blandin, G. A1 - Delcher, A. A1 - Baltz, T. A1 - Najib M. El‐Sayed A1 - Ghedin, E. VL - 23 ER - TY - JOUR T1 - The Trypanosoma cruzi L1Tc and NARTc non-LTR retrotransposons show relative site specificity for insertion. JF - Mol Biol Evol Y1 - 2006 A1 - Bringaud, Frederic A1 - Bartholomeu, Daniella C A1 - Blandin, Gaëlle A1 - Delcher, Arthur A1 - Baltz, Théo A1 - el-Sayed, Najib M A A1 - Ghedin, Elodie KW - Animals KW - DNA, Protozoan KW - DNA-(Apurinic or Apyrimidinic Site) Lyase KW - Mutagenesis, Insertional KW - Retroelements KW - Sequence Deletion KW - Trypanosoma cruzi AB -

The trypanosomatid protozoan Trypanosoma cruzi contains long autonomous (L1Tc) and short nonautonomous (NARTc) non-long terminal repeat retrotransposons. NARTc (0.25 kb) probably derived from L1Tc (4.9 kb) by 3'-deletion. It has been proposed that their apparent random distribution in the genome is related to the L1Tc-encoded apurinic/apyrimidinic endonuclease (APE) activity, which repairs modified residues. To address this question we used the T. cruzi (CL-Brener strain) genome data to analyze the distribution of all the L1Tc/NARTc elements present in contigs larger than 10 kb. This data set, which represents 0.91x sequence coverage of the haploid nuclear genome ( approximately 55 Mb), contains 419 elements, including 112 full-length L1Tc elements (14 of which are potentially functional) and 84 full-length NARTc. Approximately half of the full-length elements are flanked by a target site duplication, most of them (87%) are 12 bp long. Statistical analyses of sequences flanking the full-length elements show the same highly conserved pattern upstream of both the L1Tc and NARTc retrotransposons. The two most conserved residues are a guanine and an adenine, which flank the site where first-strand cleavage is performed by the element-encoded endonuclease activity. This analysis clearly indicates that the L1Tc and NARTc elements display relative site specificity for insertion, which suggests that the APE activity is not responsible for first-strand cleavage of the target site.

VL - 23 CP - 2 M3 - 10.1093/molbev/msj046 ER - TY - JOUR T1 - Trypanosoma cruzi mitochondrial maxicircles display species- and strain-specific variation and a conserved element in the non-coding region. JF - BMC Genomics Y1 - 2006 A1 - Westenberger, Scott J A1 - Cerqueira, Gustavo C A1 - El-Sayed, Najib M A1 - Zingales, Bianca A1 - Campbell, David A A1 - Sturm, Nancy R KW - Amino Acid Sequence KW - Animals KW - Animals, Inbred Strains KW - Base Composition KW - Conserved Sequence KW - DNA, Kinetoplast KW - Frameshifting, Ribosomal KW - Gene Deletion KW - Gene Order KW - Genetic Variation KW - Leishmania KW - Models, Biological KW - Molecular Sequence Data KW - Muscle Proteins KW - NADH Dehydrogenase KW - Open Reading Frames KW - Regulatory Elements, Transcriptional KW - RNA Editing KW - Sequence Homology, Amino Acid KW - Species Specificity KW - Trypanosoma brucei brucei KW - Trypanosoma cruzi KW - Ubiquitin-Protein Ligases KW - Untranslated Regions AB -

BACKGROUND: The mitochondrial DNA of kinetoplastid flagellates is distinctive in the eukaryotic world due to its massive size, complex form and large sequence content. Comprised of catenated maxicircles that contain rRNA and protein-coding genes and thousands of heterogeneous minicircles encoding small guide RNAs, the kinetoplast network has evolved along with an extreme form of mRNA processing in the form of uridine insertion and deletion RNA editing. Many maxicircle-encoded mRNAs cannot be translated without this post-transcriptional sequence modification.

RESULTS: We present the complete sequence and annotation of the Trypanosoma cruzi maxicircles for the CL Brener and Esmeraldo strains. Gene order is syntenic with Trypanosoma brucei and Leishmania tarentolae maxicircles. The non-coding components have strain-specific repetitive regions and a variable region that is unique for each strain with the exception of a conserved sequence element that may serve as an origin of replication, but shows no sequence identity with L. tarentolae or T. brucei. Alternative assemblies of the variable region demonstrate intra-strain heterogeneity of the maxicircle population. The extent of mRNA editing required for particular genes approximates that seen in T. brucei. Extensively edited genes were more divergent among the genera than non-edited and rRNA genes. Esmeraldo contains a unique 236-bp deletion that removes the 5'-ends of ND4 and CR4 and the intergenic region. Esmeraldo shows additional insertions and deletions outside of areas edited in other species in ND5, MURF1, and MURF2, while CL Brener has a distinct insertion in MURF2.

CONCLUSION: The CL Brener and Esmeraldo maxicircles represent two of three previously defined maxicircle clades and promise utility as taxonomic markers. Restoration of the disrupted reading frames might be accomplished by strain-specific RNA editing. Elements in the non-coding region may be important for replication, transcription, and anchoring of the maxicircle within the kinetoplast network.

VL - 7 M3 - 10.1186/1471-2164-7-60 ER - TY - JOUR T1 - Trypanosoma cruzi mitochondrial maxicircles display species- and strain-specific variation and a conserved element in the non-coding region JF - BMC GenomicsBMC Genomics Y1 - 2006 A1 - Westenberger, Scott A1 - Cerqueira, Gustavo A1 - Najib M. El‐Sayed A1 - Zingales, Bianca A1 - Campbell, David A1 - Sturm, Nancy AB - BACKGROUND:The mitochondrial DNA of kinetoplastid flagellates is distinctive in the eukaryotic world due to its massive size, complex form and large sequence content. Comprised of catenated maxicircles that contain rRNA and protein-coding genes and thousands of heterogeneous minicircles encoding small guide RNAs, the kinetoplast network has evolved along with an extreme form of mRNA processing in the form of uridine insertion and deletion RNA editing. Many maxicircle-encoded mRNAs cannot be translated without this post-transcriptional sequence modification.RESULTS:We present the complete sequence and annotation of the Trypanosoma cruzi maxicircles for the CL Brener and Esmeraldo strains. Gene order is syntenic with Trypanosoma brucei and Leishmania tarentolae maxicircles. The non-coding components have strain-specific repetitive regions and a variable region that is unique for each strain with the exception of a conserved sequence element that may serve as an origin of replication, but shows no sequence identity with L. tarentolae or T. brucei. Alternative assemblies of the variable region demonstrate intra-strain heterogeneity of the maxicircle population. The extent of mRNA editing required for particular genes approximates that seen in T. brucei. Extensively edited genes were more divergent among the genera than non-edited and rRNA genes. Esmeraldo contains a unique 236-bp deletion that removes the 5'-ends of ND4 and CR4 and the intergenic region. Esmeraldo shows additional insertions and deletions outside of areas edited in other species in ND5, MURF1, and MURF2, while CL Brener has a distinct insertion in MURF2.CONCLUSION:The CL Brener and Esmeraldo maxicircles represent two of three previously defined maxicircle clades and promise utility as taxonomic markers. Restoration of the disrupted reading frames might be accomplished by strain-specific RNA editing. Elements in the non-coding region may be important for replication, transcription, and anchoring of the maxicircle within the kinetoplast network. VL - 7 SN - 1471-2164 ER - TY - JOUR T1 - Bioinformatic Prediction of mRNA Targets of the Fragile X Mental Retardation Protein Y1 - 2005 A1 - Simola, D. F. A1 - Bucan, M. A1 - Dalva, M. A1 - Sridhar Hannenhalli A1 - Liebhaber, S. A1 - Ungar, L. ER - TY - JOUR T1 - Cholera: the killer from the deep JF - The BiochemistThe Biochemist Y1 - 2005 A1 - Rita R. Colwell AB - The current international attention to the importance ofcombating infectious diseases can provide the opportunity for a multidisciplinary approach that joins medicine with many other scientific and technological disciplines. Science and technology are major forces that have the potential to balance the world’s inequities. The connection between cholera and the environment provides a paradigm for this perspective. ER - TY - JOUR T1 - Comparative Genomics of Trypanosomatid Parasitic Protozoa JF - ScienceScience Y1 - 2005 A1 - Najib M. El‐Sayed A1 - Myler, Peter J. A1 - Blandin, Gaëlle A1 - Berriman, Matthew A1 - Crabtree, Jonathan A1 - Aggarwal, Gautam A1 - Caler, Elisabet A1 - Renauld, Hubert A1 - Worthey, Elizabeth A. A1 - Hertz-Fowler, Christiane A1 - Ghedin, Elodie A1 - Peacock, Christopher A1 - Bartholomeu, Daniella C. A1 - Haas, Brian J. A1 - Tran, Anh-Nhi A1 - Wortman, Jennifer R. A1 - Alsmark, U. Cecilia M. A1 - Angiuoli, Samuel A1 - Anupama, Atashi A1 - Badger, Jonathan A1 - Bringaud, Frederic A1 - Cadag, Eithon A1 - Carlton, Jane M. A1 - Cerqueira, Gustavo C. A1 - Creasy, Todd A1 - Delcher, Arthur L. A1 - Djikeng, Appolinaire A1 - Embley, T. Martin A1 - Hauser, Christopher A1 - Ivens, Alasdair C. A1 - Kummerfeld, Sarah K. A1 - Pereira-Leal, Jose B. A1 - Nilsson, Daniel A1 - Peterson, Jeremy A1 - Salzberg, Steven L. A1 - Shallom, Joshua A1 - Silva, Joana C. A1 - Sundaram, Jaideep A1 - Westenberger, Scott A1 - White, Owen A1 - Melville, Sara E. A1 - Donelson, John E. A1 - Andersson, Björn A1 - Stuart, Kenneth D. A1 - Hall, Neil AB - A comparison of gene content and genome architecture of Trypanosoma brucei, Trypanosoma cruzi, and Leishmania major, three related pathogens with different life cycles and disease pathology, revealed a conserved core proteome of about 6200 genes in large syntenic polycistronic gene clusters. Many species-specific genes, especially large surface antigen families, occur at nonsyntenic chromosome-internal and subtelomeric regions. Retroelements, structural RNAs, and gene family expansion are often associated with syntenic discontinuities that—along with gene divergence, acquisition and loss, and rearrangement within the syntenic regions—have shaped the genomes of each parasite. Contrary to recent reports, our analyses reveal no evidence that these species are descended from an ancestor that contained a photosynthetic endosymbiont. VL - 309 ER - TY - JOUR T1 - Critical Factors Influencing the Occurrence of Vibrio Cholerae in the Environment of Bangladesh JF - Applied and Environmental MicrobiologyAppl. Environ. Microbiol.Applied and Environmental MicrobiologyAppl. Environ. Microbiol. Y1 - 2005 A1 - Huq, Anwar A1 - Sack, R. Bradley A1 - Nizam, Azhar A1 - Longini, Ira M. A1 - Nair, G. Balakrish A1 - Ali, Afsar A1 - Morris, J. Glenn A1 - Khan, M. N. Huda A1 - Siddique, A. Kasem A1 - Yunus, Mohammed A1 - Albert, M. John A1 - Sack, David A. A1 - Rita R. Colwell AB - The occurrence of outbreaks of cholera in Africa in 1970 and in Latin America in 1991, mainly in coastal communities, and the appearance of the new serotype Vibrio cholerae O139 in India and subsequently in Bangladesh have stimulated efforts to understand environmental factors influencing the growth and geographic distribution of epidemic Vibrio cholerae serotypes. Because of the severity of recent epidemics, cholera is now being considered by some infectious disease investigators as a “reemerging” disease, prompting new work on the ecology of vibrios. Epidemiological and ecological surveillance for cholera has been under way in four rural, geographically separated locations in Bangladesh for the past 4 years, during which both clinical and environmental samples were collected at biweekly intervals. The clinical epidemiology portion of the research has been published (Sack et al., J. Infect. Dis. 187:96-101, 2003). The results of environmental sampling and analysis of the environmental and clinical data have revealed significant correlations of water temperature, water depth, rainfall, conductivity, and copepod counts with the occurrence of cholera toxin-producing bacteria (presumably V. cholerae). The lag periods between increases or decreases in units of factors, such as temperature and salinity, and occurrence of cholera correlate with biological parameters, e.g., plankton population blooms. The new information on the ecology of V. cholerae is proving useful in developing environmental models for the prediction of cholera epidemics. VL - 71 SN - 0099-2240, 1098-5336 ER - TY - JOUR T1 - Data sharing in ecology and evolution JF - Trends in Ecology & EvolutionTrends in Ecology & Evolution Y1 - 2005 A1 - Parr, Cynthia S. A1 - Michael P. Cummings VL - 20 SN - 0169-5347 ER - TY - JOUR T1 - Dynamic Querying for Pattern Identification in Microarray and Genomic Data (2003) JF - Institute for Systems Research Technical ReportsInstitute for Systems Research Technical Reports Y1 - 2005 A1 - Hochheiser, Harry A1 - Baehrecke, Eric H. A1 - Stephen M. Mount A1 - Shneiderman, Ben KW - Technical Report AB - Data sets involving linear ordered sequences are a recurring theme in bioinformatics. Dynamic query tools that support exploration of these data sets can be useful for identifying patterns of interest. This paper describes the use of one such tool TimeSearcher - to interactively explore linear sequence data sets taken from two bioinformatics problems. Microarray time course data sets involve expression levels for large numbers of genes over multiple time points. TimeSearcher can be used to interactively search these data sets for genes with expression profiles of interest. The occurrence frequencies of short sequences of DNA in aligned exons can be used to identify sequences that play a role in the pre-mRNA splicing. TimeSearcher can be used to search these data sets for candidate splicing signals. ER - TY - JOUR T1 - eGenomics: Cataloguing our Complete Genome Collection JF - Comparative and functional genomicsComparative and functional genomics Y1 - 2005 A1 - Field, Dawn A1 - Garrity, George A1 - Morrison, Norman A1 - J. Selengut A1 - Sterk, Peter A1 - Tatusova, Tatiana A1 - Thomson, Nick VL - 6 N1 - http://www.ncbi.nlm.nih.gov/pubmed/18629208?dopt=Abstract ER - TY - JOUR T1 - Enhanced position weight matrices using mixture models JF - BioinformaticsBioinformatics Y1 - 2005 A1 - Sridhar Hannenhalli A1 - Wang, L. S. AB - Motivation: Positional weight matrix (PWM) is derived from a set of experimentally determined binding sites. Here we explore whether there exist subclasses of binding sites and if the mixture of these subclass-PWMs can improve the binding site prediction. Intuitively, the subclasses correspond to either distinct binding preference of the same transcription factor in different contexts or distinct subtypes of the transcription factor.Result: We report an Expectation Maximization algorithm adapting the mixture model of Baily and Elkan. We assessed the relative merit of using two subclass-PWMs. The resulting PWMs were evaluated with respect to preferred conservation (relative to mouse) of potential sites in human promoters and expression coherence of the potential target genes. Based on 64 JASPAR vertebrate PWMs, 61–81% of the cases resulted in a higher conservation using the mixture model. Also in 98% of the cases the expression coherence was higher for the target genes of one of the subclass-PWMs. Our analysis of Reb1 sites is consistent with previously discovered subtypes using independent methods. Additionally application of our method to mutated sites for transcription factor LEU3 reveals subclasses that segregate into strongly binding and weakly binding sites with P-value of 0.008. This is the first study which attempts to quantify the subtly different binding specificities of a transcription factor on a large scale and suggests the use of a mixture of PWMs, instead of the current practice of using a single PWM, for a transcription factor. VL - 21 SN - 1367-4803, 1460-2059 ER - TY - JOUR T1 - A framework for set-oriented computation in inductive logic programming and its application in generalizing inverse entailment JF - Inductive Logic ProgrammingInductive Logic Programming Y1 - 2005 A1 - Héctor Corrada Bravo A1 - Page, D. A1 - Ramakrishnan, R. A1 - Shavlik, J. A1 - Costa, V. S. ER - TY - JOUR T1 - Generalizations of Markov model to characterize biological sequences JF - BMC BioinformaticsBMC Bioinformatics Y1 - 2005 A1 - Wang, Junwen A1 - Sridhar Hannenhalli AB - BACKGROUND:The currently used kth order Markov models estimate the probability of generating a single nucleotide conditional upon the immediately preceding (gap = 0) k units. However, this neither takes into account the joint dependency of multiple neighboring nucleotides, nor does it consider the long range dependency with gap>0.RESULT:We describe a configurable tool to explore generalizations of the standard Markov model. We evaluated whether the sequence classification accuracy can be improved by using an alternative set of model parameters. The evaluation was done on four classes of biological sequences - CpG-poor promoters, all promoters, exons and nucleosome positioning sequences. Using di- and tri-nucleotide as the model unit significantly improved the sequence classification accuracy relative to the standard single nucleotide model. In the case of nucleosome positioning sequences, optimal accuracy was achieved at a gap length of 4. Furthermore in the plot of classification accuracy versus the gap, a periodicity of 10-11 bps was observed which might indicate structural preferences in the nucleosome positioning sequence. The tool is implemented in Java and is available for download at ftp://ftp.pcbi.upenn.edu/GMM/.CONCLUSION:Markov modeling is an important component of many sequence analysis tools. We have extended the standard Markov model to incorporate joint and long range dependencies between the sequence elements. The proposed generalizations of the Markov model are likely to improve the overall accuracy of sequence analysis tools. VL - 6 SN - 1471-2105 ER - TY - JOUR T1 - The genetic map and comparative analysis with the physical map of Trypanosoma brucei JF - Nucleic acids researchNucleic Acids Research Y1 - 2005 A1 - MacLeod, A. A1 - Tweedie, A. A1 - McLellan, S. A1 - Taylor, S. A1 - Hall, N. A1 - Berriman, M. A1 - Najib M. El‐Sayed A1 - Hope, M. A1 - Turner, C. M. R. A1 - Tait, A. VL - 33 ER - TY - JOUR T1 - Genome analysis of multiple pathogenic isolates of Streptococcus agalactiae: implications for the microbial "pan-genome" JF - Proceedings of the National Academy of Sciences of the United States of AmericaProceedings of the National Academy of Sciences of the United States of America Y1 - 2005 A1 - Tettelin, Hervé A1 - Masignani, Vega A1 - Cieslewicz, Michael J. A1 - Donati, Claudio A1 - Medini, Duccio A1 - Ward, Naomi L. A1 - Angiuoli, Samuel V. A1 - Crabtree, Jonathan A1 - Jones, Amanda L. A1 - Durkin, A. Scott A1 - DeBoy, Robert T. A1 - Davidsen, Tanja M. A1 - Mora, Marirosa A1 - Scarselli, Maria A1 - Margarit y Ros, Immaculada A1 - Peterson, Jeremy D. A1 - Hauser, Christopher R. A1 - Sundaram, Jaideep P. A1 - Nelson, William C. A1 - Madupu, Ramana A1 - Brinkac, Lauren M. A1 - Dodson, Robert J. A1 - Rosovitz, Mary J. A1 - Sullivan, Steven A. A1 - Daugherty, Sean C. A1 - Haft, Daniel H. A1 - J. Selengut A1 - Gwinn, Michelle L. A1 - Zhou, Liwei A1 - Zafar, Nikhat A1 - Khouri, Hoda A1 - Radune, Diana A1 - Dimitrov, George A1 - Watkins, Kisha A1 - O'Connor, Kevin J. B. A1 - Smith, Shannon A1 - Utterback, Teresa R. A1 - White, Owen A1 - Rubens, Craig E. A1 - Grandi, Guido A1 - Madoff, Lawrence C. A1 - Kasper, Dennis L. A1 - Telford, John L. A1 - Wessels, Michael R. A1 - Rappuoli, Rino A1 - Fraser, Claire M. KW - Amino Acid Sequence KW - Bacterial Capsules KW - Base Sequence KW - Gene expression KW - Genes, Bacterial KW - Genetic Variation KW - Genome, Bacterial KW - Molecular Sequence Data KW - Phylogeny KW - sequence alignment KW - Sequence Analysis, DNA KW - Streptococcus agalactiae KW - virulence AB - The development of efficient and inexpensive genome sequencing methods has revolutionized the study of human bacterial pathogens and improved vaccine design. Unfortunately, the sequence of a single genome does not reflect how genetic variability drives pathogenesis within a bacterial species and also limits genome-wide screens for vaccine candidates or for antimicrobial targets. We have generated the genomic sequence of six strains representing the five major disease-causing serotypes of Streptococcus agalactiae, the main cause of neonatal infection in humans. Analysis of these genomes and those available in databases showed that the S. agalactiae species can be described by a pan-genome consisting of a core genome shared by all isolates, accounting for approximately 80% of any single genome, plus a dispensable genome consisting of partially shared and strain-specific genes. Mathematical extrapolation of the data suggests that the gene reservoir available for inclusion in the S. agalactiae pan-genome is vast and that unique genes will continue to be identified even after sequencing hundreds of genomes. VL - 102 N1 - http://www.ncbi.nlm.nih.gov/pubmed/16172379?dopt=Abstract ER - TY - JOUR T1 - The genome of the African trypanosome Trypanosoma brucei JF - ScienceScience Y1 - 2005 A1 - Berriman, M. A1 - Ghedin, E. A1 - Hertz-Fowler, C. A1 - Blandin, G. A1 - Renauld, H. A1 - Bartholomeu, D. C. A1 - Lennard, N. J. A1 - Caler, E. A1 - Hamlin, N. E. A1 - Haas, B. A1 - others, VL - 309 ER - TY - JOUR T1 - The genome of the protist parasite Entamoeba histolytica JF - NatureNature Y1 - 2005 A1 - Loftus, B. A1 - Anderson, I. A1 - Davies, R. A1 - Alsmark, U. C. M. A1 - Samuelson, J. A1 - Amedeo, P. A1 - Roncaglia, P. A1 - Berriman, M. A1 - Hirt, R. P. A1 - Mann, B. J. A1 - others, PB - Nature Publishing Group VL - 433 ER - TY - JOUR T1 - Genome Properties: a system for the investigation of prokaryotic genetic content for microbiology, genome annotation and comparative genomics JF - Bioinformatics (Oxford, England)Bioinformatics (Oxford, England) Y1 - 2005 A1 - Haft, Daniel H. A1 - J. Selengut A1 - Brinkac, Lauren M. A1 - Zafar, Nikhat A1 - White, Owen KW - Chromosome mapping KW - database management systems KW - Databases, Genetic KW - documentation KW - Gene Expression Profiling KW - Gene Expression Regulation KW - Genomics KW - Information Storage and Retrieval KW - Microbiological Techniques KW - natural language processing KW - Prokaryotic Cells KW - Proteome KW - signal transduction KW - software KW - User-Computer Interface KW - Vocabulary, Controlled AB - MOTIVATION: The presence or absence of metabolic pathways and structures provide a context that makes protein annotation far more reliable. Compiling such information across microbial genomes improves the functional classification of proteins and provides a valuable resource for comparative genomics. RESULTS: We have created a Genome Properties system to present key aspects of prokaryotic biology using standardized computational methods and controlled vocabularies. Properties reflect gene content, phenotype, phylogeny and computational analyses. The results of searches using hidden Markov models allow many properties to be deduced automatically, especially for families of proteins (equivalogs) conserved in function since their last common ancestor. Additional properties are derived from curation, published reports and other forms of evidence. Genome Properties system was applied to 156 complete prokaryotic genomes, and is easily mined to find differences between species, correlations between metabolic features and families of uncharacterized proteins, or relationships among properties. AVAILABILITY: Genome Properties can be found at http://www.tigr.org/Genome_Properties SUPPLEMENTARY INFORMATION: http://www.tigr.org/tigr-scripts/CMR2/genome_properties_references.spl. VL - 21 N1 - http://www.ncbi.nlm.nih.gov/pubmed/15347579?dopt=Abstract ER - TY - JOUR T1 - The genome sequence of Trypanosoma cruzi, etiologic agent of Chagas disease JF - ScienceScience Y1 - 2005 A1 - Najib M. El‐Sayed A1 - Myler, P. J. A1 - Bartholomeu, D. C. A1 - Nilsson, D. A1 - Aggarwal, G. A1 - Tran, A. N. A1 - Ghedin, E. A1 - Worthey, E. A. A1 - Delcher, A. L. A1 - Blandin, G. A1 - others, PB - American Association for the Advancement of Science VL - 309 ER - TY - JOUR T1 - Genome-Wide Analysis of Chromosomal Features Repressing Human Immunodeficiency Virus Transcription JF - Journal of VirologyJ. Virol.Journal of VirologyJ. Virol. Y1 - 2005 A1 - Lewinski, M. K. A1 - Bisgrove, D. A1 - Shinn, P. A1 - Chen, H. A1 - Hoffmann, C. A1 - Sridhar Hannenhalli A1 - Verdin, E. A1 - Berry, C. C. A1 - Ecker, J. R. A1 - Bushman, F. D. AB - We have investigated regulatory sequences in noncoding human DNA that are associated with repression of an integrated human immunodeficiency virus type 1 (HIV-1) promoter. HIV-1 integration results in the formation of precise and homogeneous junctions between viral and host DNA, but integration takes place at many locations. Thus, the variation in HIV-1 gene expression at different integration sites reports the activity of regulatory sequences at nearby chromosomal positions. Negative regulation of HIV transcription is of particular interest because of its association with maintaining HIV in a latent state in cells from infected patients. To identify chromosomal regulators of HIV transcription, we infected Jurkat T cells with an HIV-based vector transducing green fluorescent protein (GFP) and separated cells into populations containing well-expressed (GFP-positive) or poorly expressed (GFP-negative) proviruses. We then determined the chromosomal locations of the two classes by sequencing 971 junctions between viral and cellular DNA. Possible effects of endogenous cellular transcription were characterized by transcriptional profiling. Low-level GFP expression correlated with integration in (i) gene deserts, (ii) centromeric heterochromatin, and (iii) very highly expressed cellular genes. These data provide a genome-wide picture of chromosomal features that repress transcription and suggest models for transcriptional latency in cells from HIV-infected patients. VL - 79 SN - 0022-538X, 1098-5514 ER - TY - JOUR T1 - Genome-wide analysis of retroviral DNA integration JF - Nat Rev MicroNat Rev MicroNat Rev MicroNat Rev Micro Y1 - 2005 A1 - Bushman, Frederic A1 - Lewinski, Mary A1 - Ciuffi, Angela A1 - Barr, Stephen A1 - Leipzig, Jeremy A1 - Sridhar Hannenhalli A1 - Hoffmann, Christian VL - 3 SN - 1740-1526 ER - TY - JOUR T1 - Global microbial ecology of Vibrio cholerae JF - Oceans and health: pathogens in the marine environmentOceans and health: pathogens in the marine environment Y1 - 2005 A1 - Rita R. Colwell AB - The disease cholera can no longer be considered a simple equation of bacteria and human host, but represents a complex network that includes global weather patterns, aquatic reservoirs, phages, zooplankton, collective behavior of surface-attached cells, an adaptable genome, and the deep sea inter alia. This interesting characterization emerges from a view of biological systems termed biocomplexity (Colwell, 2002a, b). The holistic approach to understanding cholera integrates contributions from experts in many fields, with multiple points of view, in models for prediction, prevention, and treatment of the disease that Vibrio cholerae causes. The spiral form shown in Figure 12.1 symbolizes the nonlinear manner in which the many parts of such a model interact. It also shows that these interactions often occur across many different scales. ER - TY - JOUR T1 - Grid computing JF - EDUCAUSE ReviewEDUCAUSE Review Y1 - 2005 A1 - Michael P. Cummings A1 - Huskamp, J. C. VL - 40 ER - TY - JOUR T1 - A guild of 45 CRISPR-associated (Cas) protein families and multiple CRISPR/Cas subtypes exist in prokaryotic genomes JF - PLoS computational biologyPLOS Computational Biology Y1 - 2005 A1 - Haft, Daniel H. A1 - J. Selengut A1 - Mongodin, Emmanuel F. A1 - Nelson, Karen E. KW - Genes, Archaeal KW - Genes, Bacterial KW - Genes, Fungal KW - Genome KW - Genome, Bacterial KW - Haloarcula marismortui KW - Markov chains KW - Multigene Family KW - Oligonucleotide Array Sequence Analysis KW - Phylogeny KW - Prokaryotic Cells KW - Proteins KW - Repetitive Sequences, Nucleic Acid KW - Yersinia pestis AB - Clustered regularly interspaced short palindromic repeats (CRISPRs) are a family of DNA direct repeats found in many prokaryotic genomes. Repeats of 21-37 bp typically show weak dyad symmetry and are separated by regularly sized, nonrepetitive spacer sequences. Four CRISPR-associated (Cas) protein families, designated Cas1 to Cas4, are strictly associated with CRISPR elements and always occur near a repeat cluster. Some spacers originate from mobile genetic elements and are thought to confer "immunity" against the elements that harbor these sequences. In the present study, we have systematically investigated uncharacterized proteins encoded in the vicinity of these CRISPRs and found many additional protein families that are strictly associated with CRISPR loci across multiple prokaryotic species. Multiple sequence alignments and hidden Markov models have been built for 45 Cas protein families. These models identify family members with high sensitivity and selectivity and classify key regulators of development, DevR and DevS, in Myxococcus xanthus as Cas proteins. These identifications show that CRISPR/cas gene regions can be quite large, with up to 20 different, tandem-arranged cas genes next to a repeat cluster or filling the region between two repeat clusters. Distinctive subsets of the collection of Cas proteins recur in phylogenetically distant species and correlate with characteristic repeat periodicity. The analyses presented here support initial proposals of mobility of these units, along with the likelihood that loci of different subtypes interact with one another as well as with host cell defensive, replicative, and regulatory systems. It is evident from this analysis that CRISPR/cas loci are larger, more complex, and more heterogeneous than previously appreciated. VL - 1 N1 - http://www.ncbi.nlm.nih.gov/pubmed/16292354?dopt=Abstract ER - TY - JOUR T1 - Magic bullets and golden rules: data sampling in molecular phylogenetics JF - Zoology (Jena)Zoology (Jena) Y1 - 2005 A1 - Michael P. Cummings A1 - Meyer, A. AB - Data collection for molecular phylogenetic studies is based on samples of both genes and taxa. In an ideal world, with no limitations to resources, as many genes could be sampled as deemed necessary to address phylogenetic problems. Given limited resources in the real world, inadequate (in terms of choice of genes or number of genes) sequences or restricted taxon sampling can adversely affect the reliability or information gained in phylogenetics. Recent empirical and simulation-based studies of data sampling in molecular phylogenetics have reached differing conclusions on how to deal with these problems. Some advocated sampling more genes, others more taxa. There is certainly no 'magic bullet' that will fit all phylogenetic problems, and no specific 'golden rules' have been deduced, other than that single genes may not always contain sufficient phylogenetic information. However, several general conclusions and suggestions can be made. One suggestion is that the determination of a multiple, but moderate number (e.g., 6-10) of gene sequences might take precedence over sequencing a larger set of genes and thereby permit the sampling of more taxa for a phylogenetic study. VL - 108 ER - TY - Generic T1 - MCMC-Based Particle Filtering for Tracking a Variable Number of Interacting Targets Y1 - 2005 A1 - Zia Khan A1 - Tucker Balch A1 - Frank Dellaert JA - IEEE Transactions on Pattern Analysis and Machine Intelligence VL - 27 CP - 11 ER - TY - Generic T1 - MCMC-based particle filtering for tracking a variable number of interacting targets. Y1 - 2005 A1 - Khan, Zia A1 - Balch, Tucker A1 - Dellaert, Frank KW - algorithms KW - Animals KW - Artificial Intelligence KW - Computer simulation KW - HUMANS KW - Image Enhancement KW - Image Interpretation, Computer-Assisted KW - Information Storage and Retrieval KW - Markov chains KW - Models, Biological KW - Models, Statistical KW - Monte Carlo Method KW - Motion KW - Movement KW - Pattern Recognition, Automated KW - Subtraction Technique KW - Video Recording AB -

We describe a particle filter that effectively deals with interacting targets--targets that are influenced by the proximity and/or behavior of other targets. The particle filter includes a Markov random field (MRF) motion prior that helps maintain the identity of targets throughout an interaction, significantly reducing tracker failures. We show that this MRF prior can be easily implemented by including an additional interaction factor in the importance weights of the particle filter. However, the computational requirements of the resulting multitarget filter render it unusable for large numbers of targets. Consequently, we replace the traditional importance sampling step in the particle filter with a novel Markov chain Monte Carlo (MCMC) sampling step to obtain a more efficient MCMC-based multitarget filter. We also show how to extend this MCMC-based filter to address a variable number of interacting targets. Finally, we present both qualitative and quantitative experimental results, demonstrating that the resulting particle filters deal efficiently and effectively with complicated target interactions.

JA - IEEE Trans Pattern Anal Mach Intell VL - 27 CP - 11 M3 - 10.1109/TPAMI.2005.223 ER - TY - JOUR T1 - An Outdoor 3-d Visual Tracking System for the Study of Spatial Navigation and Memory in Rhesus Monkeys JF - Behavior Research Methods,Instruments & Computers Y1 - 2005 A1 - Zia Khan A1 - Rebecca A. Herman A1 - Kim Wallen A1 - Tucker Balch VL - 37 CP - 3 ER - TY - Generic T1 - An outdoor 3-D visual tracking system for the study of spatial navigation and memory in rhesus monkeys. Y1 - 2005 A1 - Khan, Zia A1 - Herman, Rebecca A A1 - Wallen, Kim A1 - Balch, Tucker KW - Animals KW - Behavior, Animal KW - Macaca mulatta KW - Memory KW - Models, Biological KW - Space Perception KW - Visual Perception AB -

Previous studies of the navigational abilities of nonhuman primates have largely been limited to what could be described by a human observer with a pen and paper. Consequently, we have developed a system that uses a pair of cameras to automatically obtain the three-dimensional trajectory of rhesus monkeys performing an outdoor spatial navigation and memory task. The system provides trajectories, path length, speed, and other variables that would be impossible for an unaided observer to note. From trajectory data, we computed and validated a path-length measurement. We use this measurement to compare the navigation abilities of several animals. In addition, we provide quantitative data on the accuracy of a method for automatic behavior detection. Currently, the system is being used to examine the sex differences in spatial navigation of rhesus monkeys. We expect that measures derived from the trajectory data will reveal strategies used by animals to solve spatial problems.

JA - Behav Res Methods VL - 37 CP - 3 ER - TY - JOUR T1 - Pathogenic Vibrio species in the marine and estuarine environment JF - Oceans and health: pathogens in the marine environmentOceans and health: pathogens in the marine environment Y1 - 2005 A1 - Pruzzo, C. A1 - Huq, A. A1 - Rita R. Colwell A1 - Donelli, G. AB - The genus Vibrio includes more than 30 species, at least 12 of which are pathogenic to humans and/or have been associated with foodborne diseases (Chakraborty et al., 1997). Among these species, Vibrio cholerae, serogroups O1 and O139, are the most important, since they are associated with epidemic and pandemic diarrhea outbreaks in many parts of the world (Centers for Disease Control and Prevention, 1995; Kaper et al., 1995). However, other species of vibrios capable of causing diarrheal disease in humans have received greater attention in the last decade. These include Vibrio parahaemolyticus, a leading cause of foodborne disease outbreaks in Japan and Korea (Lee et al., 2001), Vibrio vulnificus, Vibrio alginolyticus, Vibrio damsela, Vibrio fluvialis, Vibrio furnissii, Vibrio hollisae, Vibrio metschnikovii, and Vibrio mimicus (Altekruse et al., 2000; Høi et al., 1997). In the USA, Vibrio species have been estimated to be the cause of about 8000 illnesses annually (Mead et al., 1999). ER - TY - JOUR T1 - Post-transcriptional Control in Mammalian Dendrites Y1 - 2005 A1 - Simola, D. F. A1 - Dalva, M. A1 - Sridhar Hannenhalli A1 - Liebhaber, S. A1 - Bucan, M. A1 - Ungar, L. ER - TY - JOUR T1 - Promoter architecture and response to a positive regulator of archaeal transcription JF - Molecular MicrobiologyMolecular Microbiology Y1 - 2005 A1 - Ouhammouch, Mohamed A1 - Langham, Geoffrey E. A1 - Hausner, Winfried A1 - Simpson, Anjana J. A1 - Najib M. El‐Sayed A1 - Geiduschek, E. Peter AB - The archaeal transcription apparatus is chimeric: its core components (RNA polymerase and basal factors) closely resemble those of eukaryotic RNA polymerase II, but the putative archaeal transcriptional regulators are overwhelmingly of bacterial type. Particular interest attaches to how these bacterial-type effectors, especially activators, regulate a eukaryote-like transcription system. The hyperthermophilic archaeon Methanocaldococcus jannaschii encodes a potent transcriptional activator, Ptr2, related to the Lrp/AsnC family of bacterial regulators. Ptr2 activates rubredoxin 2 (rb2) transcription through a bipartite upstream activating site (UAS), and conveys its stimulatory effects on its cognate transcription machinery through direct recruitment of the TATA binding protein (TBP). A functional dissection of the highly constrained architecture of the rb2 promoter shows that a ‘one-site’ minimal UAS suffices for activation by Ptr2, and specifies the required placement of this site. The presence of such a simplified UAS upstream of the natural rubrerythrin (rbr) promoter also suffices for positive regulation by Ptr2 in vitro, and TBP recruitment remains the primary means of transcriptional activation at this promoter. VL - 56 SN - 1365-2958 ER - TY - JOUR T1 - Serendipitous discovery of Wolbachia genomes in multiple Drosophila species JF - Genome BiologyGenome Biology Y1 - 2005 A1 - Salzberg, Steven L. A1 - Hotopp, Julie C. D. A1 - Delcher, Arthur L. A1 - M. Pop A1 - Smith, Douglas R. A1 - Eisen, Michael B. A1 - Nelson, William C. AB - The Trace Archive is a repository for the raw, unanalyzed data generated by large-scale genome sequencing projects. The existence of this data offers scientists the possibility of discovering additional genomic sequences beyond those originally sequenced. In particular, if the source DNA for a sequencing project came from a species that was colonized by another organism, then the project may yield substantial amounts of genomic DNA, including near-complete genomes, from the symbiotic or parasitic organism. VL - 6 SN - 1465-6906 ER - TY - JOUR T1 - Telomere and subtelomere of Trypanosoma cruzi chromosomes are enriched in (pseudo)genes of retrotransposon hot spot and trans-sialidase-like gene families: the origins of T. cruzi telomeres. JF - Gene Y1 - 2005 A1 - Kim, Dong A1 - Chiurillo, Miguel Angel A1 - El-Sayed, Najib A1 - Jones, Kristin A1 - Santos, Márcia R M A1 - Porcile, Patricio E A1 - Andersson, Björn A1 - Myler, Peter A1 - da Silveira, Jose Franco A1 - Ramírez, José Luis KW - Amino Acid Sequence KW - Animals KW - Base Sequence KW - Chromosomes KW - Chromosomes, Artificial, Bacterial KW - DNA, Protozoan KW - Genes, Protozoan KW - Glycoproteins KW - Molecular Sequence Data KW - Multigene Family KW - Neuraminidase KW - Pseudogenes KW - Retroelements KW - Sequence Homology, Amino Acid KW - Sequence Homology, Nucleic Acid KW - Telomere KW - Trypanosoma cruzi AB -

Here, we sequenced two large telomeric regions obtained from the pathogen protozoan Trypanosoma cruzi. These sequences, together with in silico assembled contigs, allowed us to establish the general features of telomeres and subtelomeres of this parasite. Our findings can be summarized as follows: We confirmed the presence of two types of telomeric ends; subtelomeric regions appeared to be enriched in (pseudo)genes of RHS (retrotransposon hot spot), TS (trans-sialidase)-like proteins, and putative surface protein DGF-1 (dispersed gene family-1). Sequence analysis of the ts-like genes located at the telomeres suggested that T. cruzi chromosomal ends could have been the site for generation of new gp85 variants, an important adhesin molecule involved in the invasion of mammalian cells by T. cruzi. Finally, a mechanism for generation of T. cruzi telomere by chromosome breakage and telomere healing is proposed.

VL - 346 M3 - 10.1016/j.gene.2004.10.014 ER - TY - JOUR T1 - Temperature-Driven Campylobacter Seasonality in England and Wales JF - Applied and Environmental MicrobiologyAppl. Environ. Microbiol.Applied and Environmental MicrobiologyAppl. Environ. Microbiol. Y1 - 2005 A1 - Louis, Valérie R. A1 - Gillespie, Iain A. A1 - O'Brien, Sarah J. A1 - Russek-Cohen, Estelle A1 - Pearson, Andrew D. A1 - Rita R. Colwell AB - Campylobacter incidence in England and Wales between 1990 and 1999 was examined in conjunction with weather conditions. Over the 10-year interval, the average annual rate was determined to be 78.4 ± 15.0 cases per 100,000, with an upward trend. Rates were higher in males than in females, regardless of age, and highest in children less than 5 years old. Major regional differences were detected, with the highest rates in Wales and the southwest and the lowest in the southeast. The disease displayed a seasonal pattern, and increased campylobacter rates were found to be correlated with temperature. The most marked seasonal effect was observed for children under the age of 5. The seasonal pattern of campylobacter infections indicated a linkage with environmental factors rather than food sources. Therefore, public health interventions should not be restricted to food-borne approaches, and the epidemiology of the seasonal peak in human campylobacter infections may best be understood through studies in young children. VL - 71 SN - 0099-2240, 1098-5336 ER - TY - JOUR T1 - Transcriptional profiling of the hyperthermophilic methanarchaeon Methanococcus jannaschii in response to lethal heat and non-lethal cold shock. JF - Environ Microbiol Y1 - 2005 A1 - Boonyaratanakornkit, Boonchai B A1 - Simpson, Anjana J A1 - Whitehead, Timothy A A1 - Fraser, Claire M A1 - el-Sayed, Najib M A A1 - Clark, Douglas S KW - Adaptation, Physiological KW - Archaeal Proteins KW - Cold Temperature KW - Gene Expression Profiling KW - Gene Expression Regulation, Archaeal KW - Heat-Shock Proteins KW - Hot Temperature KW - Methanococcus KW - Temperature KW - Transcription, Genetic AB -

Temperature shock of the hyperthermophilic methanarchaeon Methanococcus jannaschii from its optimal growth temperature of 85 degrees C to 65 degrees C and 95 degrees C resulted in different transcriptional responses characteristic of both the direction of shock (heat or cold shock) and whether the shock was lethal. Specific outcomes of lethal heat shock to 95 degrees C included upregulation of genes encoding chaperones, and downregulation of genes encoding subunits of the H+ transporting ATP synthase. A gene encoding an alpha subunit of a putative prefoldin was also upregulated, which may comprise a novel element in the protein processing pathway in M. jannaschii. Very different responses were observed upon cold shock to 65 degrees C. These included upregulation of a gene encoding an RNA helicase and other genes involved in transcription and translation, and upregulation of genes coding for proteases and transport proteins. Also upregulated was a gene that codes for an 18 kDa FKBP-type PPIase, which may facilitate protein folding at low temperatures. Transcriptional profiling also revealed several hypothetical proteins that respond to temperature stress conditions.

VL - 7 CP - 6 M3 - 10.1111/j.1462-2920.2005.00751.x ER - TY - JOUR T1 - Transcriptional profiling of the hyperthermophilic methanarchaeon Methanococcus jannaschii in response to lethal heat and non‐lethal cold shock JF - Environmental MicrobiologyEnvironmental Microbiology Y1 - 2005 A1 - Boonyaratanakornkit, Boonchai B. A1 - Simpson, Anjana J. A1 - Whitehead, Timothy A. A1 - Fraser, Claire M. A1 - Najib M. El‐Sayed A1 - Clark, Douglas S. AB - Temperature shock of the hyperthermophilic methanarchaeon Methanococcus jannaschii from its optimal growth temperature of 85°C to 65°C and 95°C resulted in different transcriptional responses characteristic of both the direction of shock (heat or cold shock) and whether the shock was lethal. Specific outcomes of lethal heat shock to 95°C included upregulation of genes encoding chaperones, and downregulation of genes encoding subunits of the H+ transporting ATP synthase. A gene encoding an α subunit of a putative prefoldin was also upregulated, which may comprise a novel element in the protein processing pathway in M. jannaschii. Very different responses were observed upon cold shock to 65°C. These included upregulation of a gene encoding an RNA helicase and other genes involved in transcription and translation, and upregulation of genes coding for proteases and transport proteins. Also upregulated was a gene that codes for an 18 kDa FKBP-type PPIase, which may facilitate protein folding at low temperatures. Transcriptional profiling also revealed several hypothetical proteins that respond to temperature stress conditions. VL - 7 SN - 1462-2920 ER - TY - CONF T1 - What Are the Ants Doing? Vision-Based Tracking and Reconstruction of Control Programs T2 - 2005 IEEE International Conference on Robotics and AutomationProceedings of the 2005 IEEE International Conference on Robotics and Automation Y1 - 2005 A1 - Egerstedt, M. A1 - Balch, T. A1 - Dellaert, F. A1 - Delmotte, F. A1 - Khan, Z. JA - 2005 IEEE International Conference on Robotics and AutomationProceedings of the 2005 IEEE International Conference on Robotics and Automation PB - IEEE CY - Barcelona, Spain UR - http://ieeexplore.ieee.org/lpdocs/epic03/wrapper.htm?arnumber=1570762 M3 - 10.1109/ROBOT.2005.1570762 ER - TY - JOUR T1 - What the genome sequence is revealing about trypanosome antigenic variation. JF - Biochem Soc Trans Y1 - 2005 A1 - Barry, J D A1 - Marcello, L A1 - Morrison, L J A1 - Read, A F A1 - Lythgoe, K A1 - Jones, N A1 - Carrington, M A1 - Blandin, G A1 - Böhme, U A1 - Caler, E A1 - Hertz-Fowler, C A1 - Renauld, H A1 - El-Sayed, N A1 - Berriman, M KW - Animals KW - Antigens, Protozoan KW - Evolution, Molecular KW - Genetic Variation KW - Genome KW - Trypanosomatina KW - Variant Surface Glycoproteins, Trypanosoma AB -

African trypanosomes evade humoral immunity through antigenic variation, whereby they switch expression of the gene encoding their VSG (variant surface glycoprotein) coat. Switching proceeds by duplication of silent VSG genes into a transcriptionally active locus. The genome project has revealed that most of the silent archive consists of hundreds of subtelomeric VSG tandem arrays, and that most of these are not functional genes. Precedent suggests that they can contribute combinatorially to the formation of expressed, functional genes through segmental gene conversion. These findings from the genome project have major implications for evolution of the VSG archive and for transmission of the parasite in the field.

VL - 33 CP - Pt 5 M3 - 10.1042/BST20050986 ER - TY - JOUR T1 - Whole-genome sequence analysis of Pseudomonas syringae pv. phaseolicola 1448A reveals divergence among pathovars in genes involved in virulence and transposition JF - Journal of bacteriologyJournal of bacteriology Y1 - 2005 A1 - Joardar, Vinita A1 - Lindeberg, Magdalen A1 - Jackson, Robert W. A1 - J. Selengut A1 - Dodson, Robert A1 - Brinkac, Lauren M. A1 - Daugherty, Sean C. A1 - Deboy, Robert A1 - Durkin, A. Scott A1 - Giglio, Michelle Gwinn A1 - Madupu, Ramana A1 - Nelson, William C. A1 - Rosovitz, M. J. A1 - Sullivan, Steven A1 - Crabtree, Jonathan A1 - Creasy, Todd A1 - Davidsen, Tanja A1 - Haft, Dan H. A1 - Zafar, Nikhat A1 - Zhou, Liwei A1 - Halpin, Rebecca A1 - Holley, Tara A1 - Khouri, Hoda A1 - Feldblyum, Tamara A1 - White, Owen A1 - Fraser, Claire M. A1 - Chatterjee, Arun K. A1 - Cartinhour, Sam A1 - Schneider, David J. A1 - Mansfield, John A1 - Collmer, Alan A1 - Buell, C. Robin KW - Bacterial Proteins KW - DNA, Bacterial KW - Genes, Bacterial KW - Genome, Bacterial KW - Molecular Sequence Data KW - Pseudomonas syringae KW - Species Specificity KW - virulence AB - Pseudomonas syringae pv. phaseolicola, a gram-negative bacterial plant pathogen, is the causal agent of halo blight of bean. In this study, we report on the genome sequence of P. syringae pv. phaseolicola isolate 1448A, which encodes 5,353 open reading frames (ORFs) on one circular chromosome (5,928,787 bp) and two plasmids (131,950 bp and 51,711 bp). Comparative analyses with a phylogenetically divergent pathovar, P. syringae pv. tomato DC3000, revealed a strong degree of conservation at the gene and genome levels. In total, 4,133 ORFs were identified as putative orthologs in these two pathovars using a reciprocal best-hit method, with 3,941 ORFs present in conserved, syntenic blocks. Although these two pathovars are highly similar at the physiological level, they have distinct host ranges; 1448A causes disease in beans, and DC3000 is pathogenic on tomato and Arabidopsis. Examination of the complement of ORFs encoding virulence, fitness, and survival factors revealed a substantial, but not complete, overlap between these two pathovars. Another distinguishing feature between the two pathovars is their distinctive sets of transposable elements. With access to a fifth complete pseudomonad genome sequence, we were able to identify 3,567 ORFs that likely comprise the core Pseudomonas genome and 365 ORFs that are P. syringae specific. VL - 187 N1 - http://www.ncbi.nlm.nih.gov/pubmed/16159782?dopt=Abstract ER - TY - Generic T1 - Abstracting workflows: unifying bioinformatics task conceptualization and specification through Semantic Web services T2 - W3C Workshop on Semantic Web for Life Sciences Y1 - 2004 A1 - Hashmi, N. A1 - Lee, S. A1 - Michael P. Cummings JA - W3C Workshop on Semantic Web for Life Sciences CY - Cambridge, Massachusetts USA ER - TY - JOUR T1 - Acinetobacter lipases: molecular biology, biochemical properties and biotechnological potential JF - Journal of industrial microbiology & biotechnologyJournal of industrial microbiology & biotechnology Y1 - 2004 A1 - Snellman, E. A. A1 - Rita R. Colwell AB - Lipases (EC 3.1.1.3) have received increased attention recently, evidenced by the increasing amount of information about lipases in the current literature. The renewed interest in this enzyme class is due primarily to investigations of their role in pathogenesis and their increasing use in biotechnological applications [38]. Also, many microbial lipases are available as commercial products, the majority of which are used in detergents, cosmetic production, food flavoring, and organic synthesis. Lipases are valued biocatalysts because they act under mild conditions, are highly stable in organic solvents, show broad substrate specificity, and usually show high regio- and/or stereo-selectivity in catalysis. A number of lipolytic strains of Acinetobacter have been isolated from a variety of sources and their lipases possess many biochemical properties similar to those that have been developed for biotechnological applications. This review discusses the biology of lipase expression in Acinetobacter, with emphasis on those aspects relevant to potential biotechnology applications. VL - 31 ER - TY - JOUR T1 - Advances in schistosome genomics JF - Trends in ParasitologyTrends in Parasitology Y1 - 2004 A1 - Najib M. El‐Sayed A1 - Bartholomeu, Daniella A1 - Ivens, Alasdair A1 - Johnston, David A. A1 - LoVerde, Philip T. AB - In Spring 2004, the first draft of the 270 Mb genome of Schistosoma mansoni will be released. This sequence is based on the assembly and annotation of a >7.5-fold coverage, shotgun sequencing project. The key stages involved in the international collaborative efforts that have led to the generation of these sequencing data for the parasite S. mansoni are discussed here. VL - 20 SN - 1471-4922 ER - TY - RPRT T1 - Applying permutation tests to tree-based statistical models: extending the R package rpart Y1 - 2004 A1 - Michael P. Cummings A1 - Myers, D. S. A1 - Mangelson, M. AB - Tree-based statistical models are useful for evaluating relationships between predictor and response variables and for generating predictions when the response is unknown. However, current methods of constructing tree-based models do not provide a probabilistic assessment of the models produced. Here we describe our work to use permutation tests to quantitatively estimate the probability of tree-based statistical models. We have extended the rpart (recursive partitioning) package of the R system for statistical data analysis. This extension, rpart.permutation, executes the permutations in parallel, using MPI (Message Passing Interface) to greatly decrease the time necessary to complete the analysis. PB - University of Maryland Institute for Advanced Computer Studies VL - 2004-24 ER - TY - CHAP T1 - BAMBE, DnaSP, ENCprime/SeqCount, LAMARC, MacClade, MEGA, Modeltest, MrBayes, PAML, PAUP*, PHYLIP, r8s, readseq, Seq-Gen, Sites, TreeView T2 - Dictionary of Bioinformatics Y1 - 2004 A1 - Michael P. Cummings ED - Hancock, JM ED - Zvelebil, MJ JA - Dictionary of Bioinformatics PB - Wiley-Liss CY - Hoboken ER - TY - JOUR T1 - A book like its cover JF - HeredityHeredity Y1 - 2004 A1 - Michael P. Cummings KW - animal and plant breeding KW - biometrical and statistical genetics KW - cytogenetics KW - ecological KW - eukaryotes KW - Genetics KW - Genomics KW - human population genetics KW - population and evolutionary genetics KW - post-genomics AB - An official journal of the Genetics Society, Heredity publishes high-quality articles describing original research and theoretical insights in all areas of genetics. Research papers are complimented by News & Commentary articles and reviews, keeping researchers and students abreast of hot topics in the field. VL - 93 SN - 0018-067X ER - TY - JOUR T1 - A book like its cover –- The Phylogenetic Handbook: A Practical Approach to DNA and Protein Phylogeny, Edited by M. Salemi and A.-M. Vandamme JF - Heredity Y1 - 2004 A1 - Michael P. Cummings VL - 93 ER - TY - JOUR T1 - CHARACTERIZATION OF< i> Ath17, A QUANTITATIVE TRAIT LOCUS FOR ATHEROSCLEROSIS SUSCEPTIBILITY BETWEEN C57BL/6J AND 129S1/SvImJ; SINGLE-NUCLEOTIDE POLYMORPHISMS HAVE IMPORTANT IMPLICATIONS ON IDENTIFYING ATHEROSCLEROSIS MODIFIER GENES JF - Cardiovascular PathologyCardiovascular Pathology Y1 - 2004 A1 - Ishimori, N. A1 - Walsh, K. A1 - Zheng, X. A1 - Lu, F. A1 - Sridhar Hannenhalli A1 - Nusskern, D. A1 - Mural, R. A1 - Paigen, B. PB - Elsevier VL - 13 ER - TY - JOUR T1 - Comparative Genome Assembly JF - Briefings in BioinformaticsBrief BioinformBriefings in BioinformaticsBrief Bioinform Y1 - 2004 A1 - M. Pop A1 - Phillippy, Adam A1 - Delcher, Arthur L. A1 - Salzberg, Steven L. KW - Assembly KW - comparative genomics KW - open source KW - shotgun sequencing AB - One of the most complex and computationally intensive tasks of genome sequence analysis is genome assembly. Even today, few centres have the resources, in both software and hardware, to assemble a genome from the thousands or millions of individual sequences generated in a whole-genome shotgun sequencing project. With the rapid growth in the number of sequenced genomes has come an increase in the number of organisms for which two or more closely related species have been sequenced. This has created the possibility of building a comparative genome assembly algorithm, which can assemble a newly sequenced genome by mapping it onto a reference genome.We describe here a novel algorithm for comparative genome assembly that can accurately assemble a typical bacterial genome in less than four minutes on a standard desktop computer. The software is available as part of the open-source AMOS project. VL - 5 SN - 1467-5463, 1477-4054 ER - TY - JOUR T1 - Comparison of the genome of the oral pathogen Treponema denticola with other spirochete genomes JF - Proceedings of the National Academy of Sciences of the United States of AmericaProceedings of the National Academy of Sciences of the United States of America Y1 - 2004 A1 - Seshadri, Rekha A1 - Myers, Garry S. A. A1 - Tettelin, Hervé A1 - Eisen, Jonathan A. A1 - Heidelberg, John F. A1 - Dodson, Robert J. A1 - Davidsen, Tanja M. A1 - DeBoy, Robert T. A1 - Fouts, Derrick E. A1 - Haft, Dan H. A1 - J. Selengut A1 - Ren, Qinghu A1 - Brinkac, Lauren M. A1 - Madupu, Ramana A1 - Kolonay, Jamie A1 - Durkin, A. Scott A1 - Daugherty, Sean C. A1 - Shetty, Jyoti A1 - Shvartsbeyn, Alla A1 - Gebregeorgis, Elizabeth A1 - Geer, Keita A1 - Tsegaye, Getahun A1 - Malek, Joel A1 - Ayodeji, Bola A1 - Shatsman, Sofiya A1 - McLeod, Michael P. A1 - Smajs, David A1 - Howell, Jerrilyn K. A1 - Pal, Sangita A1 - Amin, Anita A1 - Vashisth, Pankaj A1 - McNeill, Thomas Z. A1 - Xiang, Qin A1 - Sodergren, Erica A1 - Baca, Ernesto A1 - Weinstock, George M. A1 - Norris, Steven J. A1 - Fraser, Claire M. A1 - Paulsen, Ian T. KW - ATP-Binding Cassette Transporters KW - Bacterial Proteins KW - Base Sequence KW - Borrelia burgdorferi KW - Genes, Bacterial KW - Genome, Bacterial KW - Leptospira interrogans KW - Models, Genetic KW - Molecular Sequence Data KW - Mouth KW - Sequence Homology, Amino Acid KW - Treponema KW - Treponema pallidum AB - We present the complete 2,843,201-bp genome sequence of Treponema denticola (ATCC 35405) an oral spirochete associated with periodontal disease. Analysis of the T. denticola genome reveals factors mediating coaggregation, cell signaling, stress protection, and other competitive and cooperative measures, consistent with its pathogenic nature and lifestyle within the mixed-species environment of subgingival dental plaque. Comparisons with previously sequenced spirochete genomes revealed specific factors contributing to differences and similarities in spirochete physiology as well as pathogenic potential. The T. denticola genome is considerably larger in size than the genome of the related syphilis-causing spirochete Treponema pallidum. The differences in gene content appear to be attributable to a combination of three phenomena: genome reduction, lineage-specific expansions, and horizontal gene transfer. Genes lost due to reductive evolution appear to be largely involved in metabolism and transport, whereas some of the genes that have arisen due to lineage-specific expansions are implicated in various pathogenic interactions, and genes acquired via horizontal gene transfer are largely phage-related or of unknown function. VL - 101 N1 - http://www.ncbi.nlm.nih.gov/pubmed/15064399?dopt=Abstract ER - TY - JOUR T1 - Divergent Gene Copies in the Asexual Class Bdelloidea (Rotifera) Separated Before the Bdelloid Radiation or Within Bdelloid Families JF - Proceedings of the National Academy of Sciences of the United States of AmericaPNASProceedings of the National Academy of Sciences of the United States of AmericaPNAS Y1 - 2004 A1 - Welch, David B. Mark A1 - Michael P. Cummings A1 - Hillis, David M. A1 - Meselson, Matthew AB - Rotifers of the asexual class Bdelloidea are unusual in possessing two or more divergent copies of every gene that has been examined. Phylogenetic analysis of the heat-shock gene hsp82 and the TATA-box-binding protein gene tbp in multiple bdelloid species suggested that for each gene, each copy belonged to one of two lineages that began to diverge before the bdelloid radiation. Such gene trees are consistent with the two lineages having descended from former alleles that began to diverge after meiotic segregation ceased or from subgenomes of an alloploid ancestor of the bdelloids. However, the original analyses of bdelloid gene-copy divergence used only a single outgroup species and were based on parsimony and neighbor joining. We have now used maximum likelihood and Bayesian inference methods and, for hsp82, multiple outgroups in an attempt to produce more robust gene trees. Here we report that the available data do not unambiguously discriminate between gene trees that root the origin of hsp82 and tbp copy divergence before the bdelloid radiation and those which indicate that the gene copies began to diverge within bdelloid families. The remarkable presence of multiple diverged gene copies in individual genomes is nevertheless consistent with the loss of sex in an ancient ancestor of bdelloids. VL - 101 SN - 0027-8424, 1091-6490 ER - TY - JOUR T1 - The Drosophila U1-70K protein is required for viability, but its arginine-rich domain is dispensable. JF - Genetics Y1 - 2004 A1 - Salz, Helen K A1 - Mancebo, Ricardo S Y A1 - Nagengast, Alexis A A1 - Speck, Olga A1 - Psotka, Mitchell A1 - Mount, Stephen M KW - Amino Acid Sequence KW - Animals KW - Animals, Genetically Modified KW - Arginine KW - Drosophila KW - Drosophila Proteins KW - Molecular Sequence Data KW - Mutation KW - Protein Structure, Tertiary KW - Ribonucleoprotein, U1 Small Nuclear KW - RNA-Binding Proteins AB -

The conserved spliceosomal U1-70K protein is thought to play a key role in RNA splicing by linking the U1 snRNP particle to regulatory RNA-binding proteins. Although these protein interactions are mediated by repeating units rich in arginines and serines (RS domains) in vitro, tests of this domain's importance in intact multicellular organisms have not been carried out. Here we report a comprehensive genetic analysis of U1-70K function in Drosophila. Consistent with the idea that U1-70K is an essential splicing factor, we find that loss of U1-70K function results in lethality during embryogenesis. Surprisingly, and contrary to the current view of U1-70K function, animals carrying a mutant U1-70K protein lacking the arginine-rich domain, which includes two embedded sets of RS dipeptide repeats, have no discernible mutant phenotype. Through double-mutant studies, however, we show that the U1-70K RS domain deletion no longer supports viability when combined with a viable mutation in another U1 snRNP component. Together our studies demonstrate that while the protein interactions mediated by the U1-70K RS domain are not essential for viability, they nevertheless contribute to an essential U1 snRNP function.

VL - 168 CP - 4 M3 - 10.1534/genetics.104.032532 ER - TY - JOUR T1 - Few amino acid positions in ıt rpoB are associated with most of the rifampin resistance in ıt Mycobacterium tuberculosis JF - BMC BioinformaticsBMC Bioinformatics Y1 - 2004 A1 - Michael P. Cummings A1 - Segal, M. R. AB - BACKGROUND: Mutations in rpoB, the gene encoding the beta subunit of DNA-dependent RNA polymerase, are associated with rifampin resistance in Mycobacterium tuberculosis. Several studies have been conducted where minimum inhibitory concentration (MIC, which is defined as the minimum concentration of the antibiotic in a given culture medium below which bacterial growth is not inhibited) of rifampin has been measured and partial DNA sequences have been determined for rpoB in different isolates of M. tuberculosis. However, no model has been constructed to predict rifampin resistance based on sequence information alone. Such a model might provide the basis for quantifying rifampin resistance status based exclusively on DNA sequence data and thus eliminate the requirements for time consuming culturing and antibiotic testing of clinical isolates. RESULTS: Sequence data for amino acid positions 511-533 of rpoB and associated MIC of rifampin for different isolates of M. tuberculosis were taken from studies examining rifampin resistance in clinical samples from New York City and throughout Japan. We used tree-based statistical methods and random forests to generate models of the relationships between rpoB amino acid sequence and rifampin resistance. The proportion of variance explained by a relatively simple tree-based cross-validated regression model involving two amino acid positions (526 and 531) is 0.679. The first partition in the data, based on position 531, results in groups that differ one hundredfold in mean MIC (1.596 micrograms/ml and 159.676 micrograms/ml). The subsequent partition based on position 526, the most variable in this region, results in a > 354-fold difference in MIC. When considered as a classification problem (susceptible or resistant), a cross-validated tree-based model correctly classified most (0.884) of the observations and was very similar to the regression model. Random forest analysis of the MIC data as a continuous variable, a regression problem, produced a model that explained 0.861 of the variance. The random forest analysis of the MIC data as discrete classes produced a model that correctly classified 0.942 of the observations with sensitivity of 0.958 and specificity of 0.885. CONCLUSIONS: Highly accurate regression and classification models of rifampin resistance can be made based on this short sequence region. Models may be better with improved (and consistent) measurements of MIC and more sequence data. VL - 5 ER - TY - CHAP T1 - Free-Living to Freewheeling: The Evolution of Vibrio cholerae from Innocence to Infamy T2 - Infectious Disease and Host-Pathogen EvolutionInfectious Disease and Host-Pathogen Evolution Y1 - 2004 A1 - Rita R. Colwell A1 - Faruque, S. M. A1 - Nair, G. B. ED - Dronamraju, Krishna R. JA - Infectious Disease and Host-Pathogen EvolutionInfectious Disease and Host-Pathogen Evolution PB - Cambridge University Press SN - 9780521820660 ER - TY - JOUR T1 - Gene synteny and evolution of genome architecture in trypanosomatids. JF - Mol Biochem Parasitol Y1 - 2004 A1 - Ghedin, Elodie A1 - Bringaud, Frederic A1 - Peterson, Jeremy A1 - Myler, Peter A1 - Berriman, Matthew A1 - Ivens, Alasdair A1 - Andersson, Björn A1 - Bontempi, Esteban A1 - Eisen, Jonathan A1 - Angiuoli, Sam A1 - Wanless, David A1 - Von Arx, Anna A1 - Murphy, Lee A1 - Lennard, Nicola A1 - Salzberg, Steven A1 - Adams, Mark D A1 - White, Owen A1 - Hall, Neil A1 - Stuart, Kenneth A1 - Fraser, Claire M A1 - el-Sayed, Najib M A KW - Animals KW - Computational Biology KW - Evolution, Molecular KW - Gene Order KW - Genome, Protozoan KW - Genomics KW - Leishmania major KW - Multigene Family KW - Recombination, Genetic KW - Retroelements KW - Selection, Genetic KW - Synteny KW - Trypanosoma brucei brucei KW - Trypanosoma cruzi KW - Trypanosomatina AB -

The trypanosomatid protozoa Trypanosoma brucei, Trypanosoma cruzi and Leishmania major are related human pathogens that cause markedly distinct diseases. Using information from genome sequencing projects currently underway, we have compared the sequences of large chromosomal fragments from each species. Despite high levels of divergence at the sequence level, these three species exhibit a striking conservation of gene order, suggesting that selection has maintained gene order among the trypanosomatids over hundreds of millions of years of evolution. The few sites of genome rearrangement between these species are marked by the presence of retrotransposon-like elements, suggesting that retrotransposons may have played an important role in shaping trypanosomatid genome organization. A degenerate retroelement was identified in L. major by examining the regions near breakage points of the synteny. This is the first such element found in L. major suggesting that retroelements were found in the common ancestor of all three species.

VL - 134 CP - 2 M3 - 10.1016/j.molbiopara.2003.11.012 ER - TY - JOUR T1 - Genome sequence of Silicibacter pomeroyi reveals adaptations to the marine environment JF - NatureNature Y1 - 2004 A1 - Moran, Mary Ann A1 - Buchan, Alison A1 - González, José M. A1 - Heidelberg, John F. A1 - Whitman, William B. A1 - Kiene, Ronald P. A1 - Henriksen, James R. A1 - King, Gary M. A1 - Belas, Robert A1 - Fuqua, Clay A1 - Brinkac, Lauren A1 - Lewis, Matt A1 - Johri, Shivani A1 - Weaver, Bruce A1 - Pai, Grace A1 - Eisen, Jonathan A. A1 - Rahe, Elisha A1 - Sheldon, Wade M. A1 - Ye, Wenying A1 - Miller, Todd R. A1 - Carlton, Jane A1 - Rasko, David A. A1 - Paulsen, Ian T. A1 - Ren, Qinghu A1 - Daugherty, Sean C. A1 - DeBoy, Robert T. A1 - Dodson, Robert J. A1 - Durkin, A. Scott A1 - Madupu, Ramana A1 - Nelson, William C. A1 - Sullivan, Steven A. A1 - Rosovitz, M. J. A1 - Haft, Daniel H. A1 - J. Selengut A1 - Ward, Naomi KW - Adaptation, Physiological KW - Carrier Proteins KW - Genes, Bacterial KW - Genome, Bacterial KW - marine biology KW - Molecular Sequence Data KW - Oceans and Seas KW - Phylogeny KW - plankton KW - RNA, Ribosomal, 16S KW - Roseobacter KW - Seawater AB - Since the recognition of prokaryotes as essential components of the oceanic food web, bacterioplankton have been acknowledged as catalysts of most major biogeochemical processes in the sea. Studying heterotrophic bacterioplankton has been challenging, however, as most major clades have never been cultured or have only been grown to low densities in sea water. Here we describe the genome sequence of Silicibacter pomeroyi, a member of the marine Roseobacter clade (Fig. 1), the relatives of which comprise approximately 10-20% of coastal and oceanic mixed-layer bacterioplankton. This first genome sequence from any major heterotrophic clade consists of a chromosome (4,109,442 base pairs) and megaplasmid (491,611 base pairs). Genome analysis indicates that this organism relies upon a lithoheterotrophic strategy that uses inorganic compounds (carbon monoxide and sulphide) to supplement heterotrophy. Silicibacter pomeroyi also has genes advantageous for associations with plankton and suspended particles, including genes for uptake of algal-derived compounds, use of metabolites from reducing microzones, rapid growth and cell-density-dependent regulation. This bacterium has a physiology distinct from that of marine oligotrophs, adding a new strategy to the recognized repertoire for coping with a nutrient-poor ocean. VL - 432 N1 - http://www.ncbi.nlm.nih.gov/pubmed/15602564?dopt=Abstract ER - TY - JOUR T1 - The genome sequence of the anaerobic, sulfate-reducing bacterium Desulfovibrio vulgaris Hildenborough JF - Nature biotechnologyNature biotechnology Y1 - 2004 A1 - Heidelberg, John F. A1 - Seshadri, Rekha A1 - Haveman, Shelley A. A1 - Hemme, Christopher L. A1 - Paulsen, Ian T. A1 - Kolonay, James F. A1 - Eisen, Jonathan A. A1 - Ward, Naomi A1 - Methe, Barbara A1 - Brinkac, Lauren M. A1 - Daugherty, Sean C. A1 - DeBoy, Robert T. A1 - Dodson, Robert J. A1 - Durkin, A. Scott A1 - Madupu, Ramana A1 - Nelson, William C. A1 - Sullivan, Steven A. A1 - Fouts, Derrick A1 - Haft, Daniel H. A1 - J. Selengut A1 - Peterson, Jeremy D. A1 - Davidsen, Tanja M. A1 - Zafar, Nikhat A1 - Zhou, Liwei A1 - Radune, Diana A1 - Dimitrov, George A1 - Hance, Mark A1 - Tran, Kevin A1 - Khouri, Hoda A1 - Gill, John A1 - Utterback, Terry R. A1 - Feldblyum, Tamara V. A1 - Wall, Judy D. A1 - Voordouw, Gerrit A1 - Fraser, Claire M. KW - Desulfovibrio vulgaris KW - Energy Metabolism KW - Genome, Bacterial KW - Molecular Sequence Data AB - Desulfovibrio vulgaris Hildenborough is a model organism for studying the energy metabolism of sulfate-reducing bacteria (SRB) and for understanding the economic impacts of SRB, including biocorrosion of metal infrastructure and bioremediation of toxic metal ions. The 3,570,858 base pair (bp) genome sequence reveals a network of novel c-type cytochromes, connecting multiple periplasmic hydrogenases and formate dehydrogenases, as a key feature of its energy metabolism. The relative arrangement of genes encoding enzymes for energy transduction, together with inferred cellular location of the enzymes, provides a basis for proposing an expansion to the 'hydrogen-cycling' model for increasing energy efficiency in this bacterium. Plasmid-encoded functions include modification of cell surface components, nitrogen fixation and a type-III protein secretion system. This genome sequence represents a substantial step toward the elucidation of pathways for reduction (and bioremediation) of pollutants such as uranium and chromium and offers a new starting point for defining this organism's complex anaerobic respiration. VL - 22 N1 - http://www.ncbi.nlm.nih.gov/pubmed/15077118?dopt=Abstract ER - TY - JOUR T1 - Hierarchical Scaffolding With Bambus JF - Genome ResearchGenome Research Y1 - 2004 A1 - M. Pop A1 - Kosack, Daniel S. A1 - Salzberg, Steven L. AB - The output of a genome assembler generally comprises a collection of contiguous DNA sequences (contigs) whose relative placement along the genome is not defined. A procedure called scaffolding is commonly used to order and orient these contigs using paired read information. This ordering of contigs is an essential step when finishing and analyzing the data from a whole-genome shotgun project. Most recent assemblers include a scaffolding module; however, users have little control over the scaffolding algorithm or the information produced. We thus developed a general-purpose scaffolder, called Bambus, which affords users significant flexibility in controlling the scaffolding parameters. Bambus was used recently to scaffold the low-coverage draft dog genome data. Most significantly, Bambus enables the use of linking data other than that inferred from mate-pair information. For example, the sequence of a completed genome can be used to guide the scaffolding of a related organism. We present several applications of Bambus: support for finishing, comparative genomics, analysis of the haplotype structure of genomes, and scaffolding of a mammalian genome at low coverage. Bambus is available as an open-source package from our Web site. VL - 14 ER - TY - JOUR T1 - Infectious disease and environment: cholera as a paradigm for waterborne disease JF - International MicrobiologyInternational Microbiology Y1 - 2004 A1 - Rita R. Colwell VL - 7 SN - 1139-6709 ER - TY - JOUR T1 - The ingi and RIME non-LTR retrotransposons are not randomly distributed in the genome of Trypanosoma brucei JF - Molecular biology and evolutionMolecular biology and evolution Y1 - 2004 A1 - Bringaud, F. A1 - Biteau, N. A1 - Zuiderwijk, E. A1 - Berriman, M. A1 - Najib M. El‐Sayed A1 - Ghedin, E. A1 - Melville, S. E. A1 - Hall, N. A1 - Baltz, T. VL - 21 ER - TY - JOUR T1 - The ingi and RIME non-LTR retrotransposons are not randomly distributed in the genome of Trypanosoma brucei. JF - Mol Biol Evol Y1 - 2004 A1 - Bringaud, Frederic A1 - Biteau, Nicolas A1 - Zuiderwijk, Eduard A1 - Berriman, Matthew A1 - El-Sayed, Najib M A1 - Ghedin, Elodie A1 - Melville, Sara E A1 - Hall, Neil A1 - Baltz, Théo KW - Amino Acid Sequence KW - Animals KW - Base Sequence KW - Consensus Sequence KW - Genome, Protozoan KW - Molecular Sequence Data KW - Retroelements KW - Sequence Analysis KW - Trypanosoma brucei brucei AB -

The ingi (long and autonomous) and RIME (short and nonautonomous) non--long-terminal repeat retrotransposons are the most abundant mobile elements characterized to date in the genome of the African trypanosome Trypanosoma brucei. These retrotransposons were thought to be randomly distributed, but a detailed and comprehensive analysis of their genomic distribution had not been performed until now. To address this question, we analyzed the ingi/RIME sequences and flanking sequences from the ongoing T. brucei genome sequencing project (TREU927/4 strain). Among the 81 ingi/RIME elements analyzed, 60% are complete, and 7% of the ingi elements (approximately 15 copies per haploid genome) appear to encode for their own transposition. The size of the direct repeat flanking the ingi/RIME retrotransposons is conserved (i.e., 12-bp), and a strong 11-bp consensus pattern precedes the 5'-direct repeat. The presence of a consensus pattern upstream of the retroelements was confirmed by the analysis of the base occurrence in 294 GSS containing 5'-adjacent ingi/RIME sequences. The conserved sequence is present upstream of ingis and RIMEs, suggesting that ingi-encoded enzymatic activities are used for retrotransposition of RIMEs, which are short nonautonomous retroelements. In conclusion, the ingi and RIME retroelements are not randomly distributed in the genome of T. brucei and are preceded by a conserved sequence, which may be the recognition site of the ingi-encoded endonuclease.

VL - 21 CP - 3 M3 - 10.1093/molbev/msh045 ER - TY - BOOK T1 - Lecture Notes in Computer ScienceComputer Vision - ECCV 2004An MCMC-Based Particle Filter for Tracking Multiple Interacting Targets Y1 - 2004 A1 - Khan, Zia A1 - Balch, Tucker A1 - Dellaert, Frank ED - Kanade, Takeo ED - Kittler, Josef ED - Kleinberg, Jon M. ED - Mattern, Friedemann ED - Mitchell, John C. ED - Nierstrasz, Oscar ED - Pandu Rangan, C. ED - Steffen, Bernhard ED - Sudan, Madhu ED - Terzopoulos, Demetri ED - Tygar, Dough ED - Vardi, Moshe Y. ED - Weikum, Gerhard ED - Pajdla, ás ED - Matas, ří PB - Springer Berlin Heidelberg CY - Berlin, Heidelberg VL - 3024 SN - 978-3-540-21981-1 UR - http://www.springerlink.com/index/10.1007/b97873http://www.springerlink.com/index/pdf/10.1007/b97873http://link.springer.com/10.1007/978-3-540-24673-2_23http://www.springerlink.com/index/pdf/10.1007/978-3-540-24673-2_23 M3 - 10.1007/b9787310.1007/978-3-540-24673-2_23 ER - TY - JOUR T1 - A Note on Efficient Computation of Haplotypes via Perfect Phylogeny JF - Journal of Computational BiologyJournal of Computational Biology Y1 - 2004 A1 - Bafna, Vineet A1 - Gusfield, Dan A1 - Sridhar Hannenhalli A1 - Yooseph, Shibu AB - The problem of inferring haplotype phase from a population of genotypes has received a lot of attention recently. This is partly due to the observation that there are many regions on human genomic DNA where genetic recombination is rare (Helmuth, 2001; Daly et al., 2001; Stephens et al., 2001; Friss et al., 2001). A Haplotype Map project has been announced by NIH to identify and characterize populations in terms of these haplotypes. Recently, Gusfield introduced the perfect phylogeny haplotyping problem, as an algorithmic implication of the no-recombination in long blocks observation, together with the standard population-genetic assumption of infinite sites. Gusfield's solution based on matroid theory was followed by direct θ(nm2 ) solutions that use simpler techniques (Bafna et al., 2003; Eskin et al., 2003), and also bound the number of solutions to the PPH problem. In this short note, we address two questions that were left open. First, can the algorithms of Bafna et al. (2003) and Eskin et al. (2003) be sped-up to O(nm + m2 ) time, which would imply an O(nm) time-bound for the PPH problem? Second, if there are multiple solutions, can we find one that is most parsimonious in terms of the number of distinct haplotypes.We give reductions that suggests that the answer to both questions is "no." For the first problem, we show that computing the output of the first step (in either method) is equivalent to Boolean matrix multiplication. Therefore, the best bound we can presently achieve is O(nmω–1), where ω ≤ 2.52 is the exponent of matrix multiplication. Thus, any linear time solution to the PPH problem likely requires a different approach. For the second problem of computing a PPH solution that minimizes the number of distinct haplotypes, we show that the problem is NP-hard using a reduction from Vertex Cover (Garey and Johnson, 1979). VL - 11 SN - 1066-5277, 1557-8666 ER - TY - JOUR T1 - Occurrence and distribution of Vibrio cholerae in the coastal environment of Peru JF - Environmental MicrobiologyEnvironmental Microbiology Y1 - 2004 A1 - Gil, Ana I. A1 - Louis, Valérie R. A1 - Rivera, Irma N. G. A1 - Lipp, Erin A1 - Huq, Anwar A1 - Lanata, Claudio F. A1 - Taylor, David N. A1 - Russek‐Cohen, Estelle A1 - Choopun, Nipa A1 - Sack, R. Bradley A1 - Rita R. Colwell AB - The occurrence and distribution of Vibrio cholerae in sea water and plankton along the coast of Peru were studied from October 1997 to June 2000, and included the 1997–98 El Niño event. Samples were collected at four sites in coastal waters off Peru at monthly intervals. Of 178 samples collected and tested, V. cholerae O1 was cultured from 10 (5.6%) samples, and V. cholerae O1 was detected by direct fluorescent antibody assay in 26 out of 159 samples tested (16.4%). Based on the number of cholera cases reported in Peru from 1997 to 2000, a significant correlation was observed between cholera incidence and elevated sea surface temperature (SST) along the coast of Peru (P < 0.001). From the results of this study, coastal sea water and zooplankton are concluded to be a reservoir for V. cholerae in Peru. The climate–cholera relationship observed for the 1997–98 El Niño year suggests that an early warning system for cholera risk can be established for Peru and neighbouring Latin American countries. VL - 6 SN - 1462-2920 ER - TY - JOUR T1 - Pandemic strains of O3:K6 Vibrio parahaemolyticus in the aquatic environment of Bangladesh JF - Canadian Journal of MicrobiologyCanadian Journal of Microbiology Y1 - 2004 A1 - Islam, M. S. A1 - Tasmin, Rizwana A1 - Khan, Sirajul I. s l a m A1 - Bakht, Habibul B. M. A1 - Mahmood, Zahid H. a y a t A1 - Rahman, M. Z. i a u r A1 - Bhuiyan, Nurul A. m i n A1 - Nishibuchi, Mitsuaki A1 - Nair, G. B. a l a k r i s h A1 - Sack, R. B. r a d l e y A1 - Huq, Anwar A1 - Rita R. Colwell A1 - Sack, David A. AB - A total of 1500 environmental strains of Vibrio parahaemolyticus, isolated from the aquatic environment of Bangladesh, were screened for the presence of a major V. parahaemolyticus virulence factor, the thermostable direct haemolysin (tdh) gene, by the colony blot hybridization method using a digoxigenin-labeled tdh gene probe. Of 1500 strains, 5 carried the tdh sequence, which was further confirmed by PCR using primers specific for the tdh gene. Examination by PCR confirmed that the 5 strains were V. parahamolyticus and lacked the thermostable direct haemolysin-related haemolysin (trh) gene, the alternative major virulence gene known to be absent in pandemic strains. All 5 strains gave positive Kanagawa phenomenon reaction with characteristic beta-haemolysis on Wagatsuma agar medium. Southern blot analysis of the HindIII-digested chromosomal DNA demonstrated, in all 5 strains, the presence of 2 tdh genes common to strains positive for Kanagawa phenomenon. However, the 5 strains were found to belong to 3 different serotypes (O3:K29, O4:K37, and O3:K6). The 2 with pandemic serotype O3:K6 gave positive results in group-specific PCR and ORF8 PCR assays, characteristics unique to the pandemic clone. Clonal variations among the 5 isolates were analyzed by comparing RAPD and ribotyping patterns. Results showed different patterns for the 3 serotypes, but the pattern was identical among the O3:K6 strains. This is the first report on the isolation of pandemic O3:K6 strains of V. parahaemolyticus from the aquatic environment of Bangladesh. VL - 50 ER - TY - CHAP T1 - PHYLIP (Phylogeny Inference Package) Y1 - 2004 A1 - Michael P. Cummings ED - Hancock, John M. ED - Zvelebil, Marketa J. PB - John Wiley & Sons, Inc. CY - Hoboken, NJ, USA M3 - 10.1002/0471650129.dob0534 ER - TY - JOUR T1 - Polylysogeny and prophage induction by secondary infection in Vibrio cholerae JF - Environmental MicrobiologyEnvironmental Microbiology Y1 - 2004 A1 - Espeland, Eric M. A1 - Lipp, Erin K. A1 - Huq, Anwar A1 - Rita R. Colwell AB - Strains of Vibrio cholerae O1, biotypes El Tor and classical, were infected with a known temperate phage (ΦP15) and monitored over a 15-day period for prophage induction. Over the course of the experiment two morphologically and three genomically distinct virus-like particles were observed from the phage-infected El Tor strain by transmission electron microscopy and field inversion gel electrophoresis, respectively, whereas only one phage, ΦP15, was observed from the infected classical strain. In the uninfected El Tor culture one prophage was spontaneously induced after 6 days. No induction in either strain was observed after treatment with mitomycin C. Data indicate that El Tor biotypes of V. cholerae may be polylysogenic and that secondary infection can promote multiple prophage induction. These traits may be important in the transfer of genetic material among V. cholerae by providing an environmentally relevant route for multiple prophage propagation and transmission. VL - 6 SN - 1462-2920 ER - TY - CONF T1 - A Rao-Blackwellized particle filter for eigentracking T2 - Proceedings of the 2004 IEEE Computer Society Conference on Computer Vision and Pattern Recognition, 2004. CVPR 2004.Proceedings of the 2004 IEEE Computer Society Conference on Computer Vision and Pattern Recognition, 2004. CVPR 2004. Y1 - 2004 A1 - Khan, Z. A1 - Balch, T. A1 - Dellaert, F. JA - Proceedings of the 2004 IEEE Computer Society Conference on Computer Vision and Pattern Recognition, 2004. CVPR 2004.Proceedings of the 2004 IEEE Computer Society Conference on Computer Vision and Pattern Recognition, 2004. CVPR 2004. PB - IEEE CY - Washington, DC, USA UR - http://ieeexplore.ieee.org/lpdocs/epic03/wrapper.htm?arnumber=1315271 M3 - 10.1109/CVPR.2004.1315271 ER - TY - JOUR T1 - Reducing storage requirements for biological sequence comparison. JF - Bioinformatics Y1 - 2004 A1 - Roberts, Michael A1 - Hayes, Wayne A1 - Hunt, Brian R A1 - Mount, Stephen M A1 - Yorke, James A KW - algorithms KW - Databases, Genetic KW - Information Storage and Retrieval KW - Numerical Analysis, Computer-Assisted KW - sequence alignment KW - Sequence Analysis AB -

MOTIVATION: Comparison of nucleic acid and protein sequences is a fundamental tool of modern bioinformatics. A dominant method of such string matching is the 'seed-and-extend' approach, in which occurrences of short subsequences called 'seeds' are used to search for potentially longer matches in a large database of sequences. Each such potential match is then checked to see if it extends beyond the seed. To be effective, the seed-and-extend approach needs to catalogue seeds from virtually every substring in the database of search strings. Projects such as mammalian genome assemblies and large-scale protein matching, however, have such large sequence databases that the resulting list of seeds cannot be stored in RAM on a single computer. This significantly slows the matching process.

RESULTS: We present a simple and elegant method in which only a small fraction of seeds, called 'minimizers', needs to be stored. Using minimizers can speed up string-matching computations by a large factor while missing only a small fraction of the matches found using all seeds.

VL - 20 CP - 18 M3 - 10.1093/bioinformatics/bth408 ER - TY - JOUR T1 - Schistosoma mansoni genome project: an update JF - Parasitology InternationalParasitology International Y1 - 2004 A1 - LoVerde, Philip T. A1 - Hirai, Hirohisa A1 - Merrick, Joseph M. A1 - Lee, Norman H. A1 - Najib M. El‐Sayed KW - Chromosome mapping KW - Gene discovery KW - Genomics KW - Schistosoma mansoni AB - A schistosome genome project was initiated by the World Health Organization in 1994 with the notion that the best prospects for identifying new targets for drugs, vaccines, and diagnostic development lie in schistosome gene discovery, development of chromosome maps, whole genome sequencing and genome analysis. Schistosoma mansoni has a haploid genome of 270 Mb contained on 8 pairs of chromosomes. It is estimated that the S. mansoni genome contains between 15 000 and 25 000 genes. There are approximately 16 689 ESTs obtained from diverse libraries representing different developmental stages of S. mansoni, deposited in the NCBI EST database. More than half of the deposited sequences correspond to genes of unknown function. Approximately 40-50% of the sequences form unique clusters, suggesting that approximately 20-25% of the total schistosome genes have been discovered. Efforts to develop low resolution chromosome maps are in progress. There is a genome sequencing program underway that will provide 3X sequence coverage of the S. mansoni genome that will result in approximately 95% gene discovery. The genomics era has provided the resources to usher in the era of functional genomics that will involve microarrays to focus on specific metabolic pathways, proteomics to identify relevant proteins and protein-protein interactions to understand critical parasite pathways. Functional genomics is expected to accelerate the development of control and treatment strategies for schistosomiasis. VL - 53 SN - 1383-5769 ER - TY - JOUR T1 - Section-level relationships of North American ıt Agalinis (Orobanchaceae) based on DNA sequence analysis of three chloroplast gene regions JF - BMC Evol BiolBMC Evol Biol Y1 - 2004 A1 - Neel, M. C. A1 - Michael P. Cummings AB - BACKGROUND: The North American Agalinis are representatives of a taxonomically difficult group that has been subject to extensive taxonomic revision from species level through higher sub-generic designations (e.g., subsections and sections). Previous presentations of relationships have been ambiguous and have not conformed to modern phylogenetic standards (e.g., were not presented as phylogenetic trees). Agalinis contains a large number of putatively rare taxa that have some degree of taxonomic uncertainty. We used DNA sequence data from three chloroplast genes to examine phylogenetic relationships among sections within the genus Agalinis Raf. (=Gerardia), and between Agalinis and closely related genera within Orobanchaceae. RESULTS: Maximum likelihood analysis of sequences data from rbcL, ndhF, and matK gene regions (total aligned length 7323 bp) yielded a phylogenetic tree with high bootstrap values for most branches. Likelihood ratio tests showed that all but a few branch lengths were significantly greater than zero, and an additional likelihood ratio test rejected the molecular clock hypothesis. Comparisons of substitution rates between gene regions based on linear models of pairwise distance estimates between taxa show both ndhF and matK evolve more rapidly than rbcL, although the there is substantial rate heterogeneity within gene regions due in part to rate differences among codon positions. CONCLUSIONS: Phylogenetic analysis supports the monophyly of Agalinis, including species formerly in Tomanthera, and this group is sister to a group formed by the genera Aureolaria, Brachystigma, Dasistoma, and Seymeria. Many of the previously described sections within Agalinis are polyphyletic, although many of the subsections appear to form natural groups. The analysis reveals a single evolutionary event leading to a reduction in chromosome number from n = 14 to n = 13 based on the sister group relationship of section Erectae and section Purpureae subsection Pedunculares. Our results establish the evolutionary distinctiveness of A. tenella from the more widespread and common A. obtusifolia. However, further data are required to clearly resolve the relationship between A. acuta and A. tenella. VL - 4 ER - TY - JOUR T1 - A semidefinite programming approach to side chain positioning with new rounding strategies JF - INFORMS Journal on ComputingINFORMS Journal on Computing Y1 - 2004 A1 - Chazelle, B. A1 - Kingsford, Carl A1 - Singh, M. VL - 16 ER - TY - JOUR T1 - Sequencing strategies for parasite genomes. JF - Methods Mol Biol Y1 - 2004 A1 - Bartholomeu, Daniella A1 - El-Sayed, Najib M KW - Animals KW - Chromosome Walking KW - Chromosomes, Artificial, Bacterial KW - Genetic Markers KW - Genome, Protozoan KW - Plasmodium falciparum AB -

Recent advances in the field of sequencing have enabled the determination of the complete nucleotide sequence of a large number of complex genomes. The complete genome sequence of the parasite Plasmodium falciparum has been published recently, and many other parasite genome initiatives are underway. Parasite genomes vary in size, nucleotide composition, polymorphism level, content, and distribution of repetitive elements. These genomic features affect the performance of sequencing strategies. As a consequence, each of the ongoing parasite genome projects has adopted distinct sequencing approaches. The degree of completeness and accuracy desired as well as available funds should be considered carefully when choosing the most appropriate sequencing strategy.

VL - 270 M3 - 10.1385/1-59259-793-9:001 ER - TY - JOUR T1 - Sequencing Strategies for Parasite Genomes JF - METHODS IN MOLECULAR BIOLOGY-CLIFTON THEN TOTOWA-METHODS IN MOLECULAR BIOLOGY-CLIFTON THEN TOTOWA- Y1 - 2004 A1 - Bartholomeu, D. A1 - Najib M. El‐Sayed A1 - Melville, S. E. VL - 270 ER - TY - CHAP T1 - Shotgun Sequence Assembly T2 - Advances in ComputersAdvances in Computers Y1 - 2004 A1 - M. Pop AB - Shotgun sequencing is the most widely used technique for determining the DNA sequence of organisms. It involves breaking up the DNA into many small pieces that can be read by automated sequencing machines, then piecing together the original genome using specialized software programs called assemblers. Due to the large amounts of data being generated and to the complex structure of most organisms' genomes, successful assembly programs rely on sophisticated algorithms based on knowledge from such diverse fields as statistics, graph theory, computer science, and computer engineering. Throughout this chapter we will describe the main computational challenges imposed by the shotgun sequencing method, and survey the most widely used assembly algorithms. JA - Advances in ComputersAdvances in Computers PB - Elsevier VL - Volume 60 SN - 0065-2458 ER - TY - JOUR T1 - Simple statistical models predict C-to-U edited sites in plant mitochondrial RNA JF - BMC BioinformaticsBMC Bioinformatics Y1 - 2004 A1 - Michael P. Cummings A1 - Myers, D. S. AB - BACKGROUND: RNA editing is the process whereby an RNA sequence is modified from the sequence of the corresponding DNA template. In the mitochondria of land plants, some cytidines are converted to uridines before translation. Despite substantial study, the molecular biological mechanism by which C-to-U RNA editing proceeds remains relatively obscure, although several experimental studies have implicated a role for cis-recognition. A highly non-random distribution of nucleotides is observed in the immediate vicinity of edited sites (within 20 nucleotides 5' and 3'), but no precise consensus motif has been identified. RESULTS: Data for analysis were derived from the the complete mitochondrial genomes of Arabidopsis thaliana, Brassica napus, and Oryza sativa; additionally, a combined data set of observations across all three genomes was generated. We selected datasets based on the 20 nucleotides 5' and the 20 nucleotides 3' of edited sites and an equivalently sized and appropriately constructed null-set of non-edited sites. We used tree-based statistical methods and random forests to generate models of C-to-U RNA editing based on the nucleotides surrounding the edited/non-edited sites and on the estimated folding energies of those regions. Tree-based statistical methods based on primary sequence data surrounding edited/non-edited sites and estimates of free energy of folding yield models with optimistic re-substitution-based estimates of approximately 0.71 accuracy, approximately 0.64 sensitivity, and approximately 0.88 specificity. Random forest analysis yielded better models and more exact performance estimates with approximately 0.74 accuracy, approximately 0.72 sensitivity, and approximately 0.81 specificity for the combined observations. CONCLUSIONS: Simple models do moderately well in predicting which cytidines will be edited to uridines, and provide the first quantitative predictive models for RNA edited sites in plant mitochondria. Our analysis shows that the identity of the nucleotide -1 to the edited C and the estimated free energy of folding for a 41 nt region surrounding the edited C are the most important variables that distinguish most edited from non-edited sites. However, the results suggest that primary sequence data and simple free energy of folding calculations alone are insufficient to make highly accurate predictions. VL - 5 ER - TY - JOUR T1 - Structural flexibility in the Burkholderia mallei genome JF - Proceedings of the National Academy of Sciences of the United States of AmericaProceedings of the National Academy of Sciences of the United States of America Y1 - 2004 A1 - Nierman, William C. A1 - DeShazer, David A1 - Kim, H. Stanley A1 - Tettelin, Hervé A1 - Nelson, Karen E. A1 - Feldblyum, Tamara A1 - Ulrich, Ricky L. A1 - Ronning, Catherine M. A1 - Brinkac, Lauren M. A1 - Daugherty, Sean C. A1 - Davidsen, Tanja D. A1 - DeBoy, Robert T. A1 - Dimitrov, George A1 - Dodson, Robert J. A1 - Durkin, A. Scott A1 - Gwinn, Michelle L. A1 - Haft, Daniel H. A1 - Khouri, Hoda A1 - Kolonay, James F. A1 - Madupu, Ramana A1 - Mohammoud, Yasmin A1 - Nelson, William C. A1 - Radune, Diana A1 - Romero, Claudia M. A1 - Sarria, Saul A1 - J. Selengut A1 - Shamblin, Christine A1 - Sullivan, Steven A. A1 - White, Owen A1 - Yu, Yan A1 - Zafar, Nikhat A1 - Zhou, Liwei A1 - Fraser, Claire M. KW - Animals KW - Base Composition KW - Base Sequence KW - Burkholderia mallei KW - Chromosomes, Bacterial KW - Cricetinae KW - Genome, Bacterial KW - Glanders KW - Liver KW - Mesocricetus KW - Molecular Sequence Data KW - Multigene Family KW - Oligonucleotide Array Sequence Analysis KW - Open Reading Frames KW - virulence AB - The complete genome sequence of Burkholderia mallei ATCC 23344 provides insight into this highly infectious bacterium's pathogenicity and evolutionary history. B. mallei, the etiologic agent of glanders, has come under renewed scientific investigation as a result of recent concerns about its past and potential future use as a biological weapon. Genome analysis identified a number of putative virulence factors whose function was supported by comparative genome hybridization and expression profiling of the bacterium in hamster liver in vivo. The genome contains numerous insertion sequence elements that have mediated extensive deletions and rearrangements of the genome relative to Burkholderia pseudomallei. The genome also contains a vast number (>12,000) of simple sequence repeats. Variation in simple sequence repeats in key genes can provide a mechanism for generating antigenic variation that may account for the mammalian host's inability to mount a durable adaptive immune response to a B. mallei infection. VL - 101 N1 - http://www.ncbi.nlm.nih.gov/pubmed/15377793?dopt=Abstract ER - TY - CHAP T1 - A Tangled Bank: Reflections on the Tree of Life and Human Health T2 - Assembling the Tree of LifeAssembling the Tree of Life Y1 - 2004 A1 - Rita R. Colwell JA - Assembling the Tree of LifeAssembling the Tree of Life PB - Oxford University Press SN - 9780195172348 ER - TY - JOUR T1 - Using the TIGR assembler in shotgun sequencing projects JF - METHODS IN MOLECULAR BIOLOGY-CLIFTON THEN TOTOWA-METHODS IN MOLECULAR BIOLOGY-CLIFTON THEN TOTOWA- Y1 - 2004 A1 - M. Pop A1 - Kosack, D. PB - Springer VL - 255 ER - TY - JOUR T1 - Variation of toxigenic Vibrio cholerae O1 in the aquatic environment of Bangladesh and its correlation with the clinical strains JF - Microbiology and immunologyMicrobiology and Immunology Y1 - 2004 A1 - Islam, M. S. A1 - Talukder, K. A. A1 - Khan, N. H. A1 - Mahmud, Z. H. A1 - Rahman, M. Z. A1 - Nair, G. B. A1 - Siddique, A. K. M. A1 - Yunus, M. A1 - Sack, D. A. A1 - Sack, R. B. A1 - Rita R. Colwell VL - 48 ER - TY - JOUR T1 - Viable but Nonculturable Vibrio Cholerae O1 in the Aquatic Environment of Argentina JF - Applied and Environmental MicrobiologyAppl. Environ. Microbiol.Applied and Environmental MicrobiologyAppl. Environ. Microbiol. Y1 - 2004 A1 - Binsztein, Norma A1 - Costagliola, Marcela C. A1 - Pichel, Mariana A1 - Jurquiza, Verónica A1 - Ramírez, Fernando C. A1 - Akselman, Rut A1 - Vacchino, Marta A1 - Huq, Anwarul A1 - Rita R. Colwell AB - In Argentina, as in other countries of Latin America, cholera has occurred in an epidemic pattern. Vibrio cholerae O1 is native to the aquatic environment, and it occurs in both culturable and viable but nonculturable (VNC) forms, the latter during interepidemic periods. This is the first report of the presence of VNC V. cholerae O1 in the estuarine and marine waters of the Río de la Plata and the Argentine shelf of the Atlantic Ocean, respectively. Employing immunofluorescence and PCR methods, we were able to detect reservoirs of V. cholerae O1 carrying the virulence-associated genes ctxA and tcpA. The VNC forms of V. cholerae O1 were identified in samples of water, phytoplankton, and zooplankton; the latter organisms were mainly the copepods Acartia tonsa, Diaptomus sp., Paracalanus crassirostris, and Paracalanus parvus. We found that under favorable conditions, the VNC form of V. cholerae can revert to the pathogenic, transmissible state. We concluded that V. cholerae O1 is a resident of Argentinean waters, as has been shown to be the case in other geographic regions of the world. VL - 70 SN - 0099-2240, 1098-5336 ER - TY - JOUR T1 - Whole genome comparisons of serotype 4b and 1/2a strains of the food-borne pathogen Listeria monocytogenes reveal new insights into the core genome components of this species JF - Nucleic acids researchNucleic Acids Research Y1 - 2004 A1 - Nelson, Karen E. A1 - Fouts, Derrick E. A1 - Mongodin, Emmanuel F. A1 - Ravel, Jacques A1 - DeBoy, Robert T. A1 - Kolonay, James F. A1 - Rasko, David A. A1 - Angiuoli, Samuel V. A1 - Gill, Steven R. A1 - Paulsen, Ian T. A1 - Peterson, Jeremy A1 - White, Owen A1 - Nelson, William C. A1 - Nierman, William A1 - Beanan, Maureen J. A1 - Brinkac, Lauren M. A1 - Daugherty, Sean C. A1 - Dodson, Robert J. A1 - Durkin, A. Scott A1 - Madupu, Ramana A1 - Haft, Daniel H. A1 - J. Selengut A1 - Van Aken, Susan A1 - Khouri, Hoda A1 - Fedorova, Nadia A1 - Forberger, Heather A1 - Tran, Bao A1 - Kathariou, Sophia A1 - Wonderling, Laura D. A1 - Uhlich, Gaylen A. A1 - Bayles, Darrell O. A1 - Luchansky, John B. A1 - Fraser, Claire M. KW - Base Composition KW - Chromosomes, Bacterial KW - DNA Transposable Elements KW - Food Microbiology KW - Genes, Bacterial KW - Genome, Bacterial KW - Genomics KW - Listeria monocytogenes KW - Meat KW - Open Reading Frames KW - Physical Chromosome Mapping KW - Polymorphism, Single Nucleotide KW - Prophages KW - Serotyping KW - Species Specificity KW - Synteny KW - virulence AB - The genomes of three strains of Listeria monocytogenes that have been associated with food-borne illness in the USA were subjected to whole genome comparative analysis. A total of 51, 97 and 69 strain-specific genes were identified in L.monocytogenes strains F2365 (serotype 4b, cheese isolate), F6854 (serotype 1/2a, frankfurter isolate) and H7858 (serotype 4b, meat isolate), respectively. Eighty-three genes were restricted to serotype 1/2a and 51 to serotype 4b strains. These strain- and serotype-specific genes probably contribute to observed differences in pathogenicity, and the ability of the organisms to survive and grow in their respective environmental niches. The serotype 1/2a-specific genes include an operon that encodes the rhamnose biosynthetic pathway that is associated with teichoic acid biosynthesis, as well as operons for five glycosyl transferases and an adenine-specific DNA methyltransferase. A total of 8603 and 105 050 high quality single nucleotide polymorphisms (SNPs) were found on the draft genome sequences of strain H7858 and strain F6854, respectively, when compared with strain F2365. Whole genome comparative analyses revealed that the L.monocytogenes genomes are essentially syntenic, with the majority of genomic differences consisting of phage insertions, transposable elements and SNPs. VL - 32 N1 - http://www.ncbi.nlm.nih.gov/pubmed/15115801?dopt=Abstract ER - TY - JOUR T1 - Whole-genome shotgun assembly and comparison of human genome assemblies JF - Proceedings of the National Academy of Sciences of the United States of AmericaProceedings of the National Academy of Sciences of the United States of America Y1 - 2004 A1 - Istrail, S. A1 - Sutton, G. G. A1 - Florea, L. A1 - Halpern, A. L. A1 - Mobarry, C. M. A1 - Lippert, R. A1 - Walenz, B. A1 - Shatkay, H. A1 - Dew, I. A1 - Miller, J. R. A1 - others, PB - National Acad Sciences VL - 101 ER - TY - JOUR T1 - X-ray crystal structure of the hypothetical phosphotyrosine phosphatase MDP-1 of the haloacid dehalogenase superfamily JF - BiochemistryBiochemistry Y1 - 2004 A1 - Peisach, Ezra A1 - J. Selengut A1 - Dunaway-Mariano, Debra A1 - Allen, Karen N. KW - Amino Acid Sequence KW - Animals KW - Binding Sites KW - Crystallography, X-Ray KW - HUMANS KW - Hydrogen-Ion Concentration KW - Hydrolases KW - Magnesium KW - Mice KW - Models, Molecular KW - Molecular Sequence Data KW - Phosphoprotein Phosphatases KW - Phosphotyrosine KW - Protein Phosphatase 1 KW - Protein Structure, Quaternary KW - Protein Structure, Tertiary KW - sequence alignment KW - Solvents KW - Substrate Specificity AB - The haloacid dehalogenase (HAD) superfamily is comprised of structurally homologous enzymes that share several conserved sequence motifs (loops I-IV) in their active site. The majority of HAD members are phosphohydrolases and may be divided into three subclasses depending on domain organization. In classes I and II, a mobile "cap" domain reorients upon substrate binding, closing the active site to bulk solvent. Members of the third class lack this additional domain. Herein, we report the 1.9 A X-ray crystal structures of a member of the third subclass, magnesium-dependent phosphatase-1 (MDP-1) both in its unliganded form and with the product analogue, tungstate, bound to the active site. The secondary structure of MDP-1 is similar to that of the "core" domain of other type I and type II HAD members with the addition of a small, 28-amino acid insert that does not close down to exclude bulk solvent in the presence of ligand. In addition, the monomeric oligomeric state of MDP-1 does not allow the participation of a second subunit in the formation and solvent protection of the active site. The binding sites for the phosphate portion of the substrate and Mg(II) cofactor are also similar to those of other HAD members, with all previously observed contacts conserved. Unlike other subclass III HAD members, MDP-1 appears to be equally able to dephosphorylate phosphotyrosine and closed-ring phosphosugars. Modeling of possible substrates in the active site of MDP-1 reveals very few potential interactions with the substrate leaving group. The mapping of conserved residues in sequences of MDP-1 from different eukaryotic organisms reveals that they colocalize to a large region on the surface of the protein outside the active site. This observation combined with the modeling studies suggests that the target of MDP-1 is most likely a phosphotyrosine in an unknown protein rather than a small sugar-based substrate. VL - 43 N1 - http://www.ncbi.nlm.nih.gov/pubmed/15461449?dopt=Abstract ER - TY - JOUR T1 - A 4-Year Study of the Epidemiology of Vibrio Cholerae in Four Rural Areas of Bangladesh JF - Journal of Infectious DiseasesJ Infect Dis.Journal of Infectious DiseasesJ Infect Dis. Y1 - 2003 A1 - Sack, R. Bradley A1 - Siddique, A. Kasem A1 - Longini, Ira M. A1 - Nizam, Azhar A1 - Yunus, Md A1 - M. Sirajul Islam A1 - Morris A1 - Ali, Afsar A1 - Huq, Anwar A1 - Nair, G. Balakrish A1 - Qadri, Firdausi A1 - Faruque, Shah M. A1 - Sack, David A. A1 - Rita R. Colwell AB - How Vibrio cholerae spreads around the world and what determines its seasonal peaks in endemic areas are not known. These features of cholera have been hypothesized to be primarily the result of environmental factors associated with aquatic habitats that can now be identified. Since 1997, fortnightly surveillance in 4 widely separated geographic locations in Bangladesh has been performed to identify patients with cholera and to collect environmental data. A total of 5670 patients (53% <5 years of age) have been studied; 14.3% had cholera (10.4% due to V. cholerae O1 El Tor, 3.8% due to O139). Both serogroups were found in all locations; outbreaks were seasonal and often occurred simultaneously. Water-use patterns showed that bathing and washing clothes in tube-well water was significantly protective in two of the sites. These data will be correlated with environmental factors, to develop a model for prediction of cholera outbreaks VL - 187 SN - 0022-1899, 1537-6613 ER - TY - JOUR T1 - ANNUAL REVIEW & FORECAST REPORTS-THE OCEANS: TO PROTECT AND TO PLOW JF - Sea TechnologySea Technology Y1 - 2003 A1 - Rita R. Colwell VL - 44 ER - TY - JOUR T1 - Characterization of a Vibrio cholerae phage isolated from the coastal water of Peru JF - Environmental MicrobiologyEnvironmental Microbiology Y1 - 2003 A1 - Talledo, Miguel A1 - Rivera, Irma N. G. A1 - Lipp, Erin K. A1 - Neale, Angela A1 - Karaolis, David A1 - Huq, Anwar A1 - Rita R. Colwell AB - A Vibrio cholerae bacteriophage, family Myoviridae, was isolated from seawater collected from the coastal water of Lima, Peru. Genome size was estimated to be 29 kbp. The temperate phage was specific to V. cholerae and infected 12/13 V. cholerae O1 strains and half of the four non-O1/non-O139 strains tested in this study. Vibrio cholerae O139 strains were resistant to infection and highest infection rates were obtained in low nutrient media amended with NaCl or prepared using seawater as diluent. VL - 5 SN - 1462-2920 ER - TY - JOUR T1 - Comparing bootstrap and posterior probability values in the four-taxon case JF - Syst BiolSyst Biol Y1 - 2003 A1 - Michael P. Cummings A1 - Handley, S. A. A1 - Myers, D. S. A1 - Reed, D. L. A1 - Rokas, A. A1 - Winka, K. AB - Assessment of the reliability of a given phylogenetic hypothesis is an important step in phylogenetic analysis. Historically, the nonparametric bootstrap procedure has been the most frequently used method for assessing the support for specific phylogenetic relationships. The recent employment of Bayesian methods for phylogenetic inference problems has resulted in clade support being expressed in terms of posterior probabilities. We used simulated data and the four-taxon case to explore the relationship between nonparametric bootstrap values (as inferred by maximum likelihood) and posterior probabilities (as inferred by Bayesian analysis). The results suggest a complex association between the two measures. Three general regions of tree space can be identified: (1) the neutral zone, where differences between mean bootstrap and mean posterior probability values are not significant, (2) near the two-branch corner, and (3) deep in the two-branch corner. In the last two regions, significant differences occur between mean bootstrap and mean posterior probability values. Whether bootstrap or posterior probability values are higher depends on the data in support of alternative topologies. Examination of star topologies revealed that both bootstrap and posterior probability values differ significantly from theoretical expectations; in particular, there are more posterior probability values in the range 0.85-1 than expected by theory. Therefore, our results corroborate the findings of others that posterior probability values are excessively high. Our results also suggest that extrapolations from single topology branch-length studies are unlikely to provide any general conclusions regarding the relationship between bootstrap and posterior probability values. VL - 52 ER - TY - JOUR T1 - Complete genome sequence and comparative analysis of the metabolically versatile Pseudomonas putida KT2440 JF - Environmental MicrobiologyEnvironmental Microbiology Y1 - 2003 A1 - Nelson, K. E. A1 - Weinel, C. A1 - Paulsen, I. T. A1 - Dodson, R. J. A1 - Hilbert, H. A1 - Martins dos Santos, V. A. P. A1 - Fouts, D. E. A1 - Gill, S. R. A1 - M. Pop A1 - Holmes, M. A1 - others, VL - 5 ER - TY - JOUR T1 - The complete genome sequence of the Arabidopsis and tomato pathogen Pseudomonas syringae pv. tomato DC3000 JF - Proceedings of the National Academy of Sciences of the United States of AmericaProceedings of the National Academy of Sciences of the United States of America Y1 - 2003 A1 - Buell, C. Robin A1 - Joardar, Vinita A1 - Lindeberg, Magdalen A1 - J. Selengut A1 - Paulsen, Ian T. A1 - Gwinn, Michelle L. A1 - Dodson, Robert J. A1 - DeBoy, Robert T. A1 - Durkin, A. Scott A1 - Kolonay, James F. A1 - Madupu, Ramana A1 - Daugherty, Sean A1 - Brinkac, Lauren A1 - Beanan, Maureen J. A1 - Haft, Daniel H. A1 - Nelson, William C. A1 - Davidsen, Tanja A1 - Zafar, Nikhat A1 - Zhou, Liwei A1 - Liu, Jia A1 - Yuan, Qiaoping A1 - Khouri, Hoda A1 - Fedorova, Nadia A1 - Tran, Bao A1 - Russell, Daniel A1 - Berry, Kristi A1 - Utterback, Teresa A1 - Aken, Susan E. van A1 - Feldblyum, Tamara V. A1 - D'Ascenzo, Mark A1 - Deng, Wen-Ling A1 - Ramos, Adela R. A1 - Alfano, James R. A1 - Cartinhour, Samuel A1 - Chatterjee, Arun K. A1 - Delaney, Terrence P. A1 - Lazarowitz, Sondra G. A1 - Martin, Gregory B. A1 - Schneider, David J. A1 - Tang, Xiaoyan A1 - Bender, Carol L. A1 - White, Owen A1 - Fraser, Claire M. A1 - Collmer, Alan KW - Arabidopsis KW - Base Sequence KW - Biological Transport KW - Genome, Bacterial KW - Lycopersicon esculentum KW - Molecular Sequence Data KW - Plant Growth Regulators KW - Plasmids KW - Pseudomonas KW - Reactive Oxygen Species KW - Siderophores KW - virulence AB - We report the complete genome sequence of the model bacterial pathogen Pseudomonas syringae pathovar tomato DC3000 (DC3000), which is pathogenic on tomato and Arabidopsis thaliana. The DC3000 genome (6.5 megabases) contains a circular chromosome and two plasmids, which collectively encode 5,763 ORFs. We identified 298 established and putative virulence genes, including several clusters of genes encoding 31 confirmed and 19 predicted type III secretion system effector proteins. Many of the virulence genes were members of paralogous families and also were proximal to mobile elements, which collectively comprise 7% of the DC3000 genome. The bacterium possesses a large repertoire of transporters for the acquisition of nutrients, particularly sugars, as well as genes implicated in attachment to plant surfaces. Over 12% of the genes are dedicated to regulation, which may reflect the need for rapid adaptation to the diverse environments encountered during epiphytic growth and pathogenesis. Comparative analyses confirmed a high degree of similarity with two sequenced pseudomonads, Pseudomonas putida and Pseudomonas aeruginosa, yet revealed 1,159 genes unique to DC3000, of which 811 lack a known function. VL - 100 N1 - http://www.ncbi.nlm.nih.gov/pubmed/12928499?dopt=Abstract ER - TY - JOUR T1 - Direct Detection of Vibrio Cholerae and ctxA in Peruvian Coastal Water and Plankton by PCR JF - Applied and Environmental MicrobiologyAppl. Environ. Microbiol.Applied and Environmental MicrobiologyAppl. Environ. Microbiol. Y1 - 2003 A1 - Lipp, Erin K. A1 - Rivera, Irma N. G. A1 - Gil, Ana I. A1 - Espeland, Eric M. A1 - Choopun, Nipa A1 - Louis, Valérie R. A1 - Russek-Cohen, Estelle A1 - Huq, Anwar A1 - Rita R. Colwell AB - Seawater and plankton samples were collected over a period of 17 months from November 1998 to March 2000 along the coast of Peru. Total DNA was extracted from water and from plankton grouped by size into two fractions (64 μm to 202 μm and >202 μm). All samples were assayed for Vibrio cholerae, V. cholerae O1, V. cholerae O139, and ctxA by PCR. Of 50 samples collected and tested, 33 (66.0%) were positive for V. cholerae in at least one of the three fractions. Of these, 62.5% (n = 32) contained V. cholerae O1; ctxA was detected in 25% (n = 20) of the V. cholerae O1-positive samples. None were positive for V. cholerae O139. Thus, PCR was successfully employed in detecting toxigenic V. cholerae directly in seawater and plankton samples and provides evidence for an environmental reservoir for this pathogen in Peruvian coastal waters. VL - 69 SN - 0099-2240, 1098-5336 ER - TY - JOUR T1 - The dog genome: survey sequencing and comparative analysis JF - ScienceScience Y1 - 2003 A1 - Kirkness, E. F. A1 - Bafna, V. A1 - Halpern, A. L. A1 - Levy, S. A1 - Remington, K. A1 - Rusch, D. B. A1 - Delcher, A. L. A1 - M. Pop A1 - Wang, W. A1 - Fraser, C. M. A1 - others, PB - American Association for the Advancement of Science VL - 301 ER - TY - Generic T1 - Dynamic querying for pattern identification in microarray and genomic data T2 - 2003 International Conference on Multimedia and Expo, 2003. ICME '03. Proceedings Y1 - 2003 A1 - Hochheiser, H. A1 - Baehrecke, E. H. A1 - Stephen M. Mount A1 - Shneiderman, Ben KW - Bioinformatics KW - data sets KW - Displays KW - dynamic querying KW - expression profiles KW - Frequency KW - Gene expression KW - genes KW - Genetics KW - genomic data KW - Genomics KW - linear ordered sequences KW - macromolecules KW - medical signal processing KW - Mice KW - Microarray KW - pattern identification KW - pattern recognition KW - premRNA splicing KW - Query processing KW - sequences KW - Signal processing KW - splicing KW - TimeSearcher AB - Data sets involving linear ordered sequences are a recurring theme in bioinformatics. Dynamic query tools that support exploration of these data sets can be useful for identifying patterns of interest. This paper describes the use of one such tool - timesearcher - to interactively explore linear sequence data sets taken from two bioinformatics problems. Microarray time course data sets involve expression levels for large numbers of genes over multiple time points. Timesearcher can be used to interactively search these data sets for genes with expression profiles of interest. The occurrence frequencies of short sequences of DNA in aligned exons can be used to identify sequences that play a role in the pre-mRNA splicing. Timesearcher can be used to search these data sets for candidate splicing signals. JA - 2003 International Conference on Multimedia and Expo, 2003. ICME '03. Proceedings PB - IEEE VL - 3 SN - 0-7803-7965-9 ER - TY - JOUR T1 - Effectiveness of conservation targets in capturing genetic diversity JF - Conserv BiolConserv Biol Y1 - 2003 A1 - Neel, M. C. A1 - Michael P. Cummings AB - Any conservation actions that preserve some populations and not others will have genetic consequences. We used empirical data from four rare plant taxa to assess these consequences in terms of how well allele numbers ( all alleles and alleles occurring at a frequency openface>0.05 in any population ) and expected heterozygosity are represented when different numbers of populations are conserved. We determined sampling distributions for these three measures of genetic diversity using Monte Carlo methods. We assessed the proportion of alleles included in the number of populations considered adequate for conservation, needed to capture all alleles, and needed to meet an accepted standard of genetic-diversity conservation of having a 90-95% probability of including all common alleles. We also assessed the number of populations necessary to obtain values of heterozygosity within +/-10% of the value obtained from all populations. Numbers of alleles were strongly affected by the number of populations sampled. Heterozygosity was only slightly less sensitive to numbers of populations than were alleles. On average, currently advocated conservation intensities represented 67-83% of all alleles and 85-93% of common alleles. The smallest number of populations to include all alleles ranged from 6 to 17 ( 42-57% ), but <0.2% of 1000 samples of these numbers of populations included them all. It was necessary to conserve 16-29 ( 53-93% ) of the sampled populations to meet the standard for common alleles. Between 20% and 64% of populations were needed to reliably represent species-level heterozygosity. Thus, higher percentages of populations are needed than are currently considered adequate to conserve genetic diversity if populations are selected without genetic data. VL - 17 ER - TY - CONF T1 - Efficient particle filter-based tracking of multiple interacting targets using an mrf-based motion model T2 - 2003 IEEE/RSJ International Conference on Intelligent Robots and Systems (IROS 2003) (Cat. No.03CH37453)Proceedings 2003 IEEE/RSJ International Conference on Intelligent Robots and Systems (IROS 2003) (Cat. No.03CH37453) Y1 - 2003 A1 - Khan, Z. A1 - Balch, T. A1 - Dellaert, F. JA - 2003 IEEE/RSJ International Conference on Intelligent Robots and Systems (IROS 2003) (Cat. No.03CH37453)Proceedings 2003 IEEE/RSJ International Conference on Intelligent Robots and Systems (IROS 2003) (Cat. No.03CH37453) PB - IEEE CY - Las Vegas, Nevada, USA UR - http://ieeexplore.ieee.org/lpdocs/epic03/wrapper.htm?arnumber=1250637 M3 - 10.1109/IROS.2003.1250637 ER - TY - JOUR T1 - Emergence and Evolution of Vibrio Cholerae O139 JF - Proceedings of the National Academy of SciencesPNASProceedings of the National Academy of SciencesPNAS Y1 - 2003 A1 - Faruque, Shah M. A1 - Sack, David A. A1 - Sack, R. Bradley A1 - Rita R. Colwell A1 - Takeda, Yoshifumi A1 - Nair, G. Balakrish AB - The emergence of Vibrio cholerae O139 Bengal during 1992–1993 was associated with large epidemics of cholera in India and Bangladesh and, initially, with a total displacement of the existing V. cholerae O1 strains. However, the O1 strains reemerged in 1994 and initiated a series of disappearance and reemergence of either of the two serogroups that was associated with temporal genetic and phenotypic changes sustained by the strains. Since the initial emergence of the O139 vibrios, new variants of the pathogen derived from multiple progenitors have been isolated and characterized. The clinical and epidemiological characteristics of these strains have been studied. Rapid genetic reassortment in O139 strains appears to be a response to the changing epidemiology of V. cholerae O1 and also a strategy for persistence in competition with strains of the O1 serogroup. The emergence of V. cholerae O139 has provided a unique opportunity to witness genetic changes in V. cholerae that may be associated with displacement of an existing serogroup by a newly emerging one and, thus, provide new insights into the epidemiology of cholera. The genetic changes and natural selection involving both environmental and host factors are likely to influence profoundly the genetics, epidemiology, and evolution of toxigenic V. cholerae, not only in the Ganges Delta region of India and Bangladesh, but also in other areas of endemic and epidemic cholera. VL - 100 SN - 0027-8424, 1091-6490 ER - TY - JOUR T1 - From terabytes to insights JF - Communications of the ACMCommunications of the ACM Y1 - 2003 A1 - Rita R. Colwell AB - For scientists and engineers tapping the NSF's high-performance cyberinfrastructure, the path to wisdom follows a route both miraculous and familiar. VL - 46 SN - 0001-0782 ER - TY - JOUR T1 - Genetic consequences of ecological reserve design guidelines: An empirical investigation JF - Conserv GenetConserv Genet Y1 - 2003 A1 - Neel, M. C. A1 - Michael P. Cummings KW - albens KW - Astragulus KW - Bernardino KW - conservation KW - design KW - diversity KW - Erigeron KW - Eriogonum KW - genetic KW - Genetics KW - goodmaniana KW - Mountains KW - ovalifolium KW - Oxytheca KW - parishii KW - plant KW - reserve KW - San KW - var. KW - vineum AB - We assessed the genetic diversity consequences of applying ecological reserve design guidelines to four federally-listed globally-rare plant species. Consequences were measured using two metrics: proportion of all alleles and of common alleles included in reserves. Common alleles were defined as those alleles having a frequency of greater than or equal to0.05 in at least one population. Four conservation professionals applied ecological reserve guidelines to choose specific populations of each species for inclusion in reserves of size 1 to N - 1, where N is the total number of populations of each species. Information regarding genetic diversity was not used in selecting populations. The resulting reserve designs were compared to random designs, and the agreement among experts was assessed using Kendall's coefficient of concordance. Application of ecological reserve design guidelines proved mostly ineffective in capturing more genetic diversity than is captured selecting populations randomly. Meeting established targets for genetic diversity, such as one advocated by the Center for Plant Conservation, required larger numbers of populations than are suggested to be sufficient. Relative performance of expert designs differed among species and was dependent on whether the proportion of all alleles or of common alleles was used as a measure of diversity. Furthermore there was no significant concordance among experts in order in which populations were incorporated into reserves as experts differed in priority they placed on individual guidelines. VL - 4 ER - TY - JOUR T1 - Genome of Geobacter sulfurreducens: metal reduction in subsurface environments JF - Science (New York, N.Y.)Science (New York, N.Y.) Y1 - 2003 A1 - Methé, B. A. A1 - Nelson, K. E. A1 - Eisen, J. A. A1 - Paulsen, I. T. A1 - Nelson, W. A1 - Heidelberg, J. F. A1 - Wu, D. A1 - Wu, M. A1 - Ward, N. A1 - Beanan, M. J. A1 - Dodson, R. J. A1 - Madupu, R. A1 - Brinkac, L. M. A1 - Daugherty, S. C. A1 - DeBoy, R. T. A1 - Durkin, A. S. A1 - Gwinn, M. A1 - Kolonay, J. F. A1 - Sullivan, S. A. A1 - Haft, D. H. A1 - J. Selengut A1 - Davidsen, T. M. A1 - Zafar, N. A1 - White, O. A1 - Tran, B. A1 - Romero, C. A1 - Forberger, H. A. A1 - Weidman, J. A1 - Khouri, H. A1 - Feldblyum, T. V. A1 - Utterback, T. R. A1 - Van Aken, S. E. A1 - Lovley, D. R. A1 - Fraser, C. M. KW - Acetates KW - Acetyl Coenzyme A KW - Aerobiosis KW - Anaerobiosis KW - Bacterial Proteins KW - Carbon KW - Chemotaxis KW - Chromosomes, Bacterial KW - Cytochromes c KW - Electron Transport KW - Energy Metabolism KW - Genes, Bacterial KW - Genes, Regulator KW - Genome, Bacterial KW - Geobacter KW - Hydrogen KW - Metals KW - Movement KW - Open Reading Frames KW - Oxidation-Reduction KW - Phylogeny AB - The complete genome sequence of Geobacter sulfurreducens, a delta-proteobacterium, reveals unsuspected capabilities, including evidence of aerobic metabolism, one-carbon and complex carbon metabolism, motility, and chemotactic behavior. These characteristics, coupled with the possession of many two-component sensors and many c-type cytochromes, reveal an ability to create alternative, redundant, electron transport networks and offer insights into the process of metal ion reduction in subsurface environments. As well as playing roles in the global cycling of metals and carbon, this organism clearly has the potential for use in bioremediation of radioactive metals and in the generation of electricity. VL - 302 N1 - http://www.ncbi.nlm.nih.gov/pubmed/14671304?dopt=Abstract ER - TY - JOUR T1 - The genome sequence of Bacillus anthracis Ames and comparison to closely related bacteria JF - NatureNature Y1 - 2003 A1 - Read, Timothy D. A1 - Peterson, Scott N. A1 - Tourasse, Nicolas A1 - Baillie, Les W. A1 - Paulsen, Ian T. A1 - Nelson, Karen E. A1 - Tettelin, Herv A1 - Fouts, Derrick E. A1 - Eisen, Jonathan A. A1 - Gill, Steven R. A1 - Holtzapple, Erik K. A1 - kstad, Ole Andreas A1 - Helgason, Erlendur A1 - Rilstone, Jennifer A1 - Wu, Martin A1 - Kolonay, James F. A1 - Beanan, Maureen J. A1 - Dodson, Robert J. A1 - Brinkac, Lauren M. A1 - Gwinn, Michelle A1 - DeBoy, Robert T. A1 - Madpu, Ramana A1 - Daugherty, Sean C. A1 - Durkin, A. Scott A1 - Haft, Daniel H. A1 - Nelson, William C. A1 - Peterson, Jeremy D. A1 - M. Pop A1 - Khouri, Hoda M. A1 - Radune, Diana A1 - Benton, Jonathan L. A1 - Mahamoud, Yasmin A1 - Jiang, Lingxia A1 - Hance, Ioana R. A1 - Weidman, Janice F. A1 - Berry, Kristi J. A1 - Plaut, Roger D. A1 - Wolf, Alex M. A1 - Watkins, Kisha L. A1 - Nierman, William C. A1 - Hazen, Alyson A1 - Cline, Robin A1 - Redmond, Caroline A1 - Thwaite, Joanne E. A1 - White, Owen A1 - Salzberg, Steven L. A1 - Thomason, Brendan A1 - Friedlander, Arthur M. A1 - Koehler, Theresa M. A1 - Hanna, Philip C. A1 - Kolst, A1 - Anne-Brit A1 - Fraser, Claire M. AB - Bacillus anthracis is an endospore-forming bacterium that causes inhalational anthrax1. Key virulence genes are found on plasmids (extra-chromosomal, circular, double-stranded DNA molecules) pXO1 (ref. 2) and pXO2 (ref. 3). To identify additional genes that might contribute to virulence, we analysed the complete sequence of the chromosome of B. anthracis Ames (about 5.23 megabases). We found several chromosomally encoded proteins that may contribute to pathogenicity—including haemolysins, phospholipases and iron acquisition functions—and identified numerous surface proteins that might be important targets for vaccines and drugs. Almost all these putative chromosomal virulence and surface proteins have homologues in Bacillus cereus, highlighting the similarity of B. anthracis to near-neighbours that are not associated with anthrax4. By performing a comparative genome hybridization of 19 B. cereus and Bacillus thuringiensis strains against a B. anthracis DNA microarray, we confirmed the general similarity of chromosomal genes among this group of close relatives. However, we found that the gene sequences of pXO1 and pXO2 were more variable between strains, suggesting plasmid mobility in the group. The complete sequence of B. anthracis is a step towards a better understanding of anthrax pathogenesis. VL - 423 SN - 0028-0836 N1 - [eacute]
[Oslash] ER - TY - JOUR T1 - Improving the Arabidopsis genome annotation using maximal transcript alignment assemblies. JF - Nucleic Acids Res Y1 - 2003 A1 - Haas, Brian J A1 - Delcher, Arthur L A1 - Mount, Stephen M A1 - Wortman, Jennifer R A1 - Smith, Roger K A1 - Hannick, Linda I A1 - Maiti, Rama A1 - Ronning, Catherine M A1 - Rusch, Douglas B A1 - Town, Christopher D A1 - Salzberg, Steven L A1 - White, Owen KW - algorithms KW - Alternative Splicing KW - Arabidopsis KW - DNA, Complementary KW - Expressed Sequence Tags KW - Genome, Plant KW - Introns KW - Plant Proteins KW - RNA, Plant KW - sequence alignment KW - software KW - Transcription, Genetic KW - Untranslated Regions AB -

The spliced alignment of expressed sequence data to genomic sequence has proven a key tool in the comprehensive annotation of genes in eukaryotic genomes. A novel algorithm was developed to assemble clusters of overlapping transcript alignments (ESTs and full-length cDNAs) into maximal alignment assemblies, thereby comprehensively incorporating all available transcript data and capturing subtle splicing variations. Complete and partial gene structures identified by this method were used to improve The Institute for Genomic Research Arabidopsis genome annotation (TIGR release v.4.0). The alignment assemblies permitted the automated modeling of several novel genes and >1000 alternative splicing variations as well as updates (including UTR annotations) to nearly half of the approximately 27 000 annotated protein coding genes. The algorithm of the Program to Assemble Spliced Alignments (PASA) tool is described, as well as the results of automated updates to Arabidopsis gene annotations.

VL - 31 CP - 19 ER - TY - JOUR T1 - Method of DNA extraction and application of multiplex polymerase chain reaction to detect toxigenic Vibrio cholerae O1 and O139 from aquatic ecosystems JF - Environmental MicrobiologyEnvironmental Microbiology Y1 - 2003 A1 - Rivera, Irma N. G. A1 - Lipp, Erin K. A1 - Gil, Ana A1 - Choopun, Nipa A1 - Huq, Anwar A1 - Rita R. Colwell AB - Vibrio cholerae is a free-living bacterium found in water and in association with plankton. V. cholerae non-O1/non-O139 strains are frequently isolated from aquatic ecosystems worldwide. Less frequently isolated are V. cholerae O1 and V. cholerae O139, the aetiological agents of cholera. These strains have two main virulence-associated factors, cholera toxin (CT) and toxin co-regulated pilus (TCP). By extracting total DNA from aquatic samples, the presence of pathogenic strains can be determined quickly and used to improve a microbiological risk assessment for cholera in coastal areas. Some methods suggested for DNA extraction from water samples are not applicable to all water types. We describe here a method for DNA extraction from coastal water and a multiplex polymerase chain reaction (PCR) for O1 and O139 serogroups. DNA extraction was successfully accomplished from 117 sea water samples collected from coastal areas of Perú, Brazil and the USA. DNA concentration in all samples varied from 20 ng to 480 µg µl−1. The sensitivity of the DNA extraction method was 100 V. cholerae cells in 250 ml of water. The specificity of multiplex O1/O139 PCR was investigated by analysing 120 strains of V. cholerae, Vibrio and other Bacteria species. All V. cholerae O1 and O139 tested were positive. For cholera surveillance of aquatic environments and ballast water, total DNA extraction, followed by V. cholerae PCR, and O1/O139 serogroup and tcpA/ctxA genes by multiplex PCR offers an efficient system, permitting risk analysis for cholera in coastal areas. VL - 5 SN - 1462-2920 ER - TY - JOUR T1 - Necessity is the mother of invention: a simple grid computing system using commodity tools JF - J Parallel Distr ComJ Parallel Distr Com Y1 - 2003 A1 - Myers, D. S. A1 - Michael P. Cummings KW - Apache KW - computing KW - distributed KW - Grid KW - HTTP KW - java KW - Linux KW - Perl KW - SQL KW - Unix KW - XML-RPC AB - Access to sufficient resources is a barrier to scientific progress for many researchers facing large computational problems. Gaining access to large-scale resources (i.e., university-wide or federally supported computer centers) can be difficult, given their limited availability, particular architectures, and request/review/approval cycles. Simultaneously, researchers often find themselves with access to workstations and older clusters overlooked by their owners in favor of newer hardware. Software to tie these resources into a coherent Grid, however, has been problematic. Here, we describe our experiences building a Grid computing system to conduct a large-scale simulation study using "borrowed" computing resources distributed over a wide area. Using standard software components, we have produced a Grid computing system capable of coupling several hundred processors spanning multiple continents and administrative domains. We believe that this system fills an important niche between a closely coupled local system and a heavyweight, highly customized wide area system. (C) 2003 Elsevier Science (USA). All rights reserved. VL - 63 ER - TY - JOUR T1 - Pathogenic Potential of Environmental Vibrio Cholerae Strains Carrying Genetic Variants of the Toxin-Coregulated Pilus Pathogenicity Island JF - Infection and ImmunityInfect. Immun.Infection and ImmunityInfect. Immun. Y1 - 2003 A1 - Faruque, Shah M. A1 - Kamruzzaman, M. A1 - Meraj, Ismail M. A1 - Chowdhury, Nityananda A1 - Nair, G. Balakrish A1 - Sack, R. Bradley A1 - Rita R. Colwell A1 - Sack, David A. AB - The major virulence factors of toxigenic Vibrio cholerae are cholera toxin (CT), which is encoded by a lysogenic bacteriophage (CTXΦ), and toxin-coregulated pilus (TCP), an essential colonization factor which is also the receptor for CTXΦ. The genes for the biosynthesis of TCP are part of a larger genetic element known as the TCP pathogenicity island. To assess their pathogenic potential, we analyzed environmental strains of V. cholerae carrying genetic variants of the TCP pathogenicity island for colonization of infant mice, susceptibility to CTXΦ, and diarrheagenicity in adult rabbits. Analysis of 14 environmental strains, including 3 strains carrying a new allele of the tcpA gene, 9 strains carrying a new allele of the toxT gene, and 2 strains carrying conventional tcpA and toxT genes, showed that all strains colonized infant mice with various efficiencies in competition with a control El Tor biotype strain of V. cholerae O1. Five of the 14 strains were susceptible to CTXΦ, and these transductants produced CT and caused diarrhea in adult rabbits. These results suggested that the new alleles of the tcpA and toxT genes found in environmental strains of V. cholerae encode biologically active gene products. Detection of functional homologs of the TCP island genes in environmental strains may have implications for understanding the origin and evolution of virulence genes of V. cholerae. VL - 71 SN - 0019-9567, 1098-5522 ER - TY - JOUR T1 - Persistence of adhesive properties in Vibrio cholerae after long‐term exposure to sea water JF - Environmental MicrobiologyEnvironmental Microbiology Y1 - 2003 A1 - Pruzzo, Carla A1 - Tarsi, Renato A1 - Del Mar Lleò, Maria A1 - Signoretto, Caterina A1 - Zampini, Massimiliano A1 - Pane, Luigi A1 - Rita R. Colwell A1 - Canepari, Pietro AB - The effect of exposure to artificial sea water (ASW) on the ability of classical Vibrio cholerae O1 cells to interact with chitin-containing substrates and human intestinal cells was studied. Incubation of vibrios in ASW at 5°C and 18°C resulted in two kinds of cell responses: the viable but non-culturable (VBNC) state (i.e. <0.1 colony forming unit ml−1) at 5°C, and starvation (i.e. maintenance of culturability of the population) at 18°C. The latter remained rod shaped and, after 40 days’ incubation, presented a 47–58% reduction in the number of cells attached to chitin, a 48–53% reduction in the number of bacteria adhering to copepods, and a 48–54% reduction in the number of bacteria adhering to human cultured intestinal cells, compared to control cells not suspended in ASW. Bacteria suspended in ASW at 5°C became coccoid and, after 40 days, showed 34–42% fewer cells attached to chitin, 52–55% fewer adhering to copep-ods, and 45–48% fewer cells adhering to intestinal cell monolayers, compared to controls. Sarkosyl-insoluble membrane proteins that bind chitin particles were isolated and analysed by SDS-PAGE. After 40 days incubation in ASW at both 5°C and 18°C vibrios expressed chitin-binding ligands similar to bacteria harvested in the stationary growth phase. It is concluded that as vibrios do not lose adhesive properties after long-term exposure to ASW, it is important to include methods for VBNC bacteria when testing environmental and clinical samples for purposes of public health safety. VL - 5 SN - 1462-2920 ER - TY - JOUR T1 - Phylogenetic analysis reveals five independent transfers of the chloroplast gene ıt rbcL to the mitochondrial genome in angiosperms JF - Curr GenetCurr Genet Y1 - 2003 A1 - Michael P. Cummings A1 - Nugent, J. M. A1 - Olmstead, R. G. A1 - Palmer, J. D. AB - We used the chloroplast gene rbcL as a model to study the frequency and relative timing of transfer of chloroplast sequences to the mitochondrial genome. Southern blot survey of 20 mitochondrial DNAs confirmed three previously reported groups of plants containing rbcL in their mitochondrion, while PCR studies identified a new mitochondrial rbcL. Published and newly determined mitochondrial and chloroplast rbcL sequences were used to reconstruct rbcL phylogeny. The results imply five or six separate interorganellar transfers of rbcL among the angiosperms examined, and hundreds of successful transfers across all flowering plants. By taxonomic criteria, the crucifer transfer is the most ancient, two separate transfers within the grass family are of intermediate ancestry, and the morning-glory transfer is most recent. All five mitochondrial copies of rbcL examined exhibit insertion and/or deletion events that disrupt the reading frame (three are grossly truncated); and all are elevated in the proportion of nonsynonymous substitutions, providing clear evidence that these sequences are pseudogenes. VL - 43 ER - TY - JOUR T1 - Predictability of Vibrio Cholerae in Chesapeake Bay JF - Applied and Environmental MicrobiologyAppl. Environ. Microbiol.Applied and Environmental MicrobiologyAppl. Environ. Microbiol. Y1 - 2003 A1 - Louis, Valérie R. A1 - Russek-Cohen, Estelle A1 - Choopun, Nipa A1 - Rivera, Irma N. G. A1 - Gangle, Brian A1 - Jiang, Sunny C. A1 - Rubin, Andrea A1 - Patz, Jonathan A. A1 - Huq, Anwar A1 - Rita R. Colwell AB - Vibrio cholerae is autochthonous to natural waters and can pose a health risk when it is consumed via untreated water or contaminated shellfish. The correlation between the occurrence of V. cholerae in Chesapeake Bay and environmental factors was investigated over a 3-year period. Water and plankton samples were collected monthly from five shore sampling sites in northern Chesapeake Bay (January 1998 to February 2000) and from research cruise stations on a north-south transect (summers of 1999 and 2000). Enrichment was used to detect culturable V. cholerae, and 21.1% (n = 427) of the samples were positive. As determined by serology tests, the isolates, did not belong to serogroup O1 or O139 associated with cholera epidemics. A direct fluorescent-antibody assay was used to detect V. cholerae O1, and 23.8% (n = 412) of the samples were positive. V. cholerae was more frequently detected during the warmer months and in northern Chesapeake Bay, where the salinity is lower. Statistical models successfully predicted the presence of V. cholerae as a function of water temperature and salinity. Temperatures above 19°C and salinities between 2 and 14 ppt yielded at least a fourfold increase in the number of detectable V. cholerae. The results suggest that salinity variation in Chesapeake Bay or other parameters associated with Susquehanna River inflow contribute to the variability in the occurrence of V. cholerae and that salinity is a useful indicator. Under scenarios of global climate change, increased climate variability, accompanied by higher stream flow rates and warmer temperatures, could favor conditions that increase the occurrence of V. cholerae in Chesapeake Bay. VL - 69 SN - 0099-2240, 1098-5336 ER - TY - JOUR T1 - Reduction of Cholera in Bangladeshi Villages by Simple Filtration JF - Proceedings of the National Academy of SciencesPNASProceedings of the National Academy of SciencesPNAS Y1 - 2003 A1 - Rita R. Colwell A1 - Huq, Anwar A1 - M. Sirajul Islam A1 - K. M. A. Aziz A1 - Yunus, M. A1 - N. Huda Khan A1 - A. Mahmud A1 - Sack, R. Bradley A1 - Nair, G. B. A1 - J. Chakraborty A1 - Sack, David A. A1 - E. Russek-Cohen AB - Based on results of ecological studies demonstrating that Vibrio cholerae, the etiological agent of epidemic cholera, is commensal to zooplankton, notably copepods, a simple filtration procedure was developed whereby zooplankton, most phytoplankton, and particulates >20 μm were removed from water before use. Effective deployment of this filtration procedure, from September 1999 through July 2002 in 65 villages of rural Bangladesh, of which the total population for the entire study comprised ≈133,000 individuals, yielded a 48% reduction in cholera (P < 0.005) compared with the control. VL - 100 SN - 0027-8424, 1091-6490 ER - TY - JOUR T1 - The sequence and analysis of Trypanosoma brucei chromosome II JF - Nucleic acids researchNucleic Acids Research Y1 - 2003 A1 - Najib M. El‐Sayed A1 - Ghedin, E. A1 - Song, J. A1 - MacLeod, A. A1 - Bringaud, F. A1 - Larkin, C. A1 - Wanless, D. A1 - Peterson, J. A1 - Hou, L. A1 - Taylor, S. A1 - others, VL - 31 ER - TY - JOUR T1 - The sequence and analysis of Trypanosoma brucei chromosome II. JF - Nucleic Acids Res Y1 - 2003 A1 - el-Sayed, Najib M A A1 - Ghedin, Elodie A1 - Song, Jinming A1 - MacLeod, Annette A1 - Bringaud, Frederic A1 - Larkin, Christopher A1 - Wanless, David A1 - Peterson, Jeremy A1 - Hou, Lihua A1 - Taylor, Sonya A1 - Tweedie, Alison A1 - Biteau, Nicolas A1 - Khalak, Hanif G A1 - Lin, Xiaoying A1 - Mason, Tanya A1 - Hannick, Linda A1 - Caler, Elisabet A1 - Blandin, Gaëlle A1 - Bartholomeu, Daniella A1 - Simpson, Anjana J A1 - Kaul, Samir A1 - Zhao, Hong A1 - Pai, Grace A1 - Van Aken, Susan A1 - Utterback, Teresa A1 - Haas, Brian A1 - Koo, Hean L A1 - Umayam, Lowell A1 - Suh, Bernard A1 - Gerrard, Caroline A1 - Leech, Vanessa A1 - Qi, Rong A1 - Zhou, Shiguo A1 - Schwartz, David A1 - Feldblyum, Tamara A1 - Salzberg, Steven A1 - Tait, Andrew A1 - Turner, C Michael R A1 - Ullu, Elisabetta A1 - White, Owen A1 - Melville, Sara A1 - Adams, Mark D A1 - Fraser, Claire M A1 - Donelson, John E KW - Animals KW - Antigens, Protozoan KW - Chromosome mapping KW - Chromosomes KW - DNA, Protozoan KW - Gene Duplication KW - Genes, Protozoan KW - Molecular Sequence Data KW - Pseudogenes KW - Recombination, Genetic KW - Sequence Analysis, DNA KW - Trypanosoma brucei brucei AB -

We report here the sequence of chromosome II from Trypanosoma brucei, the causative agent of African sleeping sickness. The 1.2-Mb pairs encode about 470 predicted genes organised in 17 directional clusters on either strand, the largest cluster of which has 92 genes lined up over a 284-kb region. An analysis of the GC skew reveals strand compositional asymmetries that coincide with the distribution of protein-coding genes, suggesting these asymmetries may be the result of transcription-coupled repair on coding versus non-coding strand. A 5-cM genetic map of the chromosome reveals recombinational 'hot' and 'cold' regions, the latter of which is predicted to include the putative centromere. One end of the chromosome consists of a 250-kb region almost exclusively composed of RHS (pseudo)genes that belong to a newly characterised multigene family containing a hot spot of insertion for retroelements. Interspersed with the RHS genes are a few copies of truncated RNA polymerase pseudogenes as well as expression site associated (pseudo)genes (ESAGs) 3 and 4, and 76 bp repeats. These features are reminiscent of a vestigial variant surface glycoprotein (VSG) gene expression site. The other end of the chromosome contains a 30-kb array of VSG genes, the majority of which are pseudogenes, suggesting that this region may be a site for modular de novo construction of VSG gene diversity during transposition/gene conversion events.

VL - 31 CP - 16 ER - TY - JOUR T1 - Sex-lethal splicing autoregulation in vivo: interactions between SEX-LETHAL, the U1 snRNP and U2AF underlie male exon skipping. JF - Development Y1 - 2003 A1 - Nagengast, Alexis A A1 - Stitzinger, Shane M A1 - Tseng, Chin-Hsiu A1 - Mount, Stephen M A1 - Salz, Helen K KW - Alternative Splicing KW - Amino Acid Sequence KW - Animals KW - Animals, Genetically Modified KW - Drosophila melanogaster KW - Drosophila Proteins KW - Exons KW - Female KW - Gene Expression Regulation, Developmental KW - Genes, Insect KW - Homeostasis KW - Male KW - Models, Genetic KW - Molecular Sequence Data KW - Nuclear Proteins KW - Point Mutation KW - Ribonucleoprotein, U1 Small Nuclear KW - Ribonucleoproteins KW - RNA Splicing KW - RNA-Binding Proteins KW - Sequence Homology, Amino Acid KW - Sex Differentiation AB -

Alternative splicing of the Sex-lethal pre-mRNA has long served as a model example of a regulated splicing event, yet the mechanism by which the female-specific SEX-LETHAL RNA-binding protein prevents inclusion of the translation-terminating male exon is not understood. Thus far, the only general splicing factor for which there is in vivo evidence for a regulatory role in the pathway leading to male-exon skipping is sans-fille (snf), a protein component of the spliceosomal U1 and U2 snRNPs. Its role, however, has remained enigmatic because of questions about whether SNF acts as part of an intact snRNP or a free protein. We provide evidence that SEX-LETHAL interacts with SANS-FILLE in the context of the U1 snRNP, through the characterization of a point mutation that interferes with both assembly into the U1 snRNP and complex formation with SEX-LETHAL. Moreover, we find that SEX-LETHAL associates with other integral U1 snRNP components, and we provide genetic evidence to support the biological relevance of these physical interactions. Similar genetic and biochemical approaches also link SEX-LETHAL with the heterodimeric splicing factor, U2AF. These studies point specifically to a mechanism by which SEX-LETHAL represses splicing by interacting with these key splicing factors at both ends of the regulated male exon. Moreover, because U2AF and the U1 snRNP are only associated transiently with the pre-mRNA during the course of spliceosome assembly, our studies are difficult to reconcile with the current model that proposes that the SEX-LETHAL blocks splicing at the second catalytic step, and instead argue that the SEX-LETHAL protein acts after splice site recognition, but before catalysis begins.

VL - 130 CP - 3 ER - TY - JOUR T1 - The TIGRFAMs database of protein families JF - Nucleic acids researchNucleic Acids Research Y1 - 2003 A1 - Haft, Daniel H. A1 - J. Selengut A1 - White, Owen KW - Animals KW - Databases, Protein KW - Markov chains KW - Mixed Function Oxygenases KW - Phylogeny KW - Proteins KW - Pyruvate Carboxylase KW - Sequence Homology, Amino Acid AB - TIGRFAMs is a collection of manually curated protein families consisting of hidden Markov models (HMMs), multiple sequence alignments, commentary, Gene Ontology (GO) assignments, literature references and pointers to related TIGRFAMs, Pfam and InterPro models. These models are designed to support both automated and manually curated annotation of genomes. TIGRFAMs contains models of full-length proteins and shorter regions at the levels of superfamilies, subfamilies and equivalogs, where equivalogs are sets of homologous proteins conserved with respect to function since their last common ancestor. The scope of each model is set by raising or lowering cutoff scores and choosing members of the seed alignment to group proteins sharing specific function (equivalog) or more general properties. The overall goal is to provide information with maximum utility for the annotation process. TIGRFAMs is thus complementary to Pfam, whose models typically achieve broad coverage across distant homologs but end at the boundaries of conserved structural domains. The database currently contains over 1600 protein families. TIGRFAMs is available for searching or downloading at www.tigr.org/TIGRFAMs. VL - 31 N1 - http://www.ncbi.nlm.nih.gov/pubmed/12520025?dopt=Abstract ER - TY - JOUR T1 - The transcription factor Eyes absent is a protein tyrosine phosphatase JF - NatureNature Y1 - 2003 A1 - Tootle, Tina L. A1 - Silver, Serena J. A1 - Davies, Erin L. A1 - Newman, Victoria A1 - Latek, Robert R. A1 - Mills, Ishara A. A1 - J. Selengut A1 - Parlikar, Beth E. W. A1 - Rebay, Ilaria KW - Amino Acid Motifs KW - Amino Acid Sequence KW - Animals KW - Antibodies, Phospho-Specific KW - Drosophila melanogaster KW - Drosophila Proteins KW - Embryonic Induction KW - eye KW - Eye Proteins KW - Gene Expression Regulation KW - Kinetics KW - Mice KW - Models, Molecular KW - Molecular Sequence Data KW - Mutation KW - Phosphorylation KW - Protein Conformation KW - Protein Tyrosine Phosphatases KW - Substrate Specificity KW - Transcription Factors AB - Post-translational modifications provide sensitive and flexible mechanisms to dynamically modulate protein function in response to specific signalling inputs. In the case of transcription factors, changes in phosphorylation state can influence protein stability, conformation, subcellular localization, cofactor interactions, transactivation potential and transcriptional output. Here we show that the evolutionarily conserved transcription factor Eyes absent (Eya) belongs to the phosphatase subgroup of the haloacid dehalogenase (HAD) superfamily, and propose a function for it as a non-thiol-based protein tyrosine phosphatase. Experiments performed in cultured Drosophila cells and in vitro indicate that Eyes absent has intrinsic protein tyrosine phosphatase activity and can autocatalytically dephosphorylate itself. Confirming the biological significance of this function, mutations that disrupt the phosphatase active site severely compromise the ability of Eyes absent to promote eye specification and development in Drosophila. Given the functional importance of phosphorylation-dependent modulation of transcription factor activity, this evidence for a nuclear transcriptional coactivator with intrinsic phosphatase activity suggests an unanticipated method of fine-tuning transcriptional regulation. VL - 426 N1 - http://www.ncbi.nlm.nih.gov/pubmed/14628053?dopt=Abstract ER - TY - JOUR T1 - Transcriptional regulation of protein complexes and biological pathways JF - Mammalian GenomeMammalian Genome Y1 - 2003 A1 - Sridhar Hannenhalli A1 - Levy, Samuel AB - The cis-element profile (or cis-profile) of a gene refers to the collection of transcription factor binding sites (TFBS) regulating the transcription of the gene. Underlying the various published studies that attempt to discover cis-elements in the vicinity of co-expressed genes via pattern detection algorithms, there is an implicit assumption that a correlation exists between co-expressed genes and their cis-profiles. In this study, we show that the cis-similarity, defined as the proportion of shared TFBS between two cis-element profiles, is higher for functionally linked interacting proteins as well as for members of a signal transduction pathway. A similar analysis of the enzymes catalyzing the conversion of adjacent substrates to products in a collection of metabolic pathways, did not reveal higher cis-similarity. The analysis is based on three distinct sources of publicly available data, namely, 1) the BIND database of interacting proteins, 2) known interactions in NMDAR protein complex, 3) the apoptosis pathway and nine pathways related to metabolism of cofactors and vitamins all from KEGG. Additionally, we analyze the cis-element profiles of all the genes in the glutamate receptor (GR) sub-complex of NMDAR complex to detect a set of cis-elements that occur adjacent to a majority of the genes. We show that most of the corresponding transcription factors are known to be involved in GR regulation by comparing our findings with the published biomedical literature. In addition, we were able to detect transcripts whose gene products associate with GR by searching for transcripts that share the same regulatory signals as those detected for GR. This suggests a novel computational methodology for constructing high-order gene regulatory models and detecting co-regulated gene products. VL - 14 SN - 0938-8990 ER - TY - JOUR T1 - 1.375-approximation algorithm for sorting by reversals JF - Algorithms—ESA 2002Algorithms—ESA 2002 Y1 - 2002 A1 - Berman, P. A1 - Sridhar Hannenhalli A1 - Karpinski, M. PB - Springer ER - TY - JOUR T1 - Analysis of 16S-23S rRNA intergenic spacer of Vibrio cholerae and Vibrio mimicus for detection of these species JF - METHODS IN MOLECULAR BIOLOGYMETHODS IN MOLECULAR BIOLOGY Y1 - 2002 A1 - Chun, J. A1 - Rivera, I. N. G. A1 - Rita R. Colwell VL - 179 ER - TY - JOUR T1 - Analysis of stage-specific gene expression in the bloodstream and the procyclic form of Trypanosoma brucei using a genomic DNA-microarray. JF - Mol Biochem Parasitol Y1 - 2002 A1 - Diehl, Susanne A1 - Diehl, Frank A1 - El-Sayed, Najib M A1 - Clayton, Christine A1 - Hoheisel, Jörg D KW - Animals KW - Blotting, Northern KW - Escherichia coli KW - Gene expression KW - Gene Expression Profiling KW - Genes, Protozoan KW - HUMANS KW - Life Cycle Stages KW - Molecular Sequence Data KW - Oligonucleotide Array Sequence Analysis KW - Polymerase Chain Reaction KW - Transcription, Genetic KW - Trypanosoma brucei brucei AB -

A microarray comprising 21,024 different PCR products spotted on glass slides was constructed for gene expression studies on Trypanosoma brucei. The arrayed fragments were generated from a T. brucei shotgun clone library, which had been prepared from randomly sheared and size-fractionated genomic DNA. For the identification of stage-specific gene activity, total RNA from in vitro cultures of the human, long slender form and the insect, procyclic form of the parasite was labelled and hybridised to the microarray. Approximately 75% of the genomic fragments produced a signal and about 2% exhibited significant differences between the transcript levels in the bloodstream and procyclic forms. A few results were confirmed by Northern blot analysis or reverse-transcription and PCR. Three hundred differentially regulated clones have been selected for sequencing. So far, of 33 clones that showed about 2-fold or more over-expression in bloodstream forms, 15 contained sequences similar to those of VSG expression sites and at least six others appeared non-protein-coding. Of 29 procyclic-specific clones, at least eight appeared not to be protein-coding. A surprisingly large proportion of known regulated genes was already identified in this small sample, and some new ones were found, illustrating the utility of genomic arrays.

VL - 123 CP - 2 ER - TY - JOUR T1 - Analysis of stage-specific gene expression in the bloodstream and the procyclic form of Trypanosoma brucei using a genomic DNA-microarray JF - Molecular and Biochemical ParasitologyMolecular and Biochemical Parasitology Y1 - 2002 A1 - Diehl, Susanne A1 - Diehl, Frank A1 - Najib M. El‐Sayed A1 - Clayton, Christine A1 - Hoheisel, Jörg D. KW - Expression KW - Gene KW - Microarray KW - Regulation KW - Trypanosoma brucei AB - A microarray comprising 21[punctuation space]024 different PCR products spotted on glass slides was constructed for gene expression studies on Trypanosoma brucei. The arrayed fragments were generated from a T. brucei shotgun clone library, which had been prepared from randomly sheared and size-fractionated genomic DNA. For the identification of stage-specific gene activity, total RNA from in vitro cultures of the human, long slender form and the insect, procyclic form of the parasite was labelled and hybridised to the microarray. Approximately 75% of the genomic fragments produced a signal and about 2% exhibited significant differences between the transcript levels in the bloodstream and procyclic forms. A few results were confirmed by Northern blot analysis or reverse-transcription and PCR. Three hundred differentially regulated clones have been selected for sequencing. So far, of 33 clones that showed about 2-fold or more over-expression in bloodstream forms, 15 contained sequences similar to those of VSG expression sites and at least six others appeared non-protein-coding. Of 29 procyclic-specific clones, at least eight appeared not to be protein-coding. A surprisingly large proportion of known regulated genes was already identified in this small sample, and some new ones were found, illustrating the utility of genomic arrays. VL - 123 SN - 0166-6851 ER - TY - JOUR T1 - Characterization of Pseudoalteromonas citrea and P. nigrifaciens Isolated from Different Ecological Habitats Based on REP-PCR Genomic Fingerprints JF - Systematic and Applied MicrobiologySystematic and Applied Microbiology Y1 - 2002 A1 - Ivanova, Elena P. A1 - Matte, Glavur R. A1 - Matte, Maria H. A1 - Coenye, Tom A1 - Huq, Anwarul A1 - Rita R. Colwell KW - biogeography KW - BOX-PCR KW - ERIC KW - Pseudoalteromonas KW - REP AB - SummaryDNA primers corresponding to conserved repetitive interspersed genomic motifs and PCR were used to show that REP, ERIC and BOX-like DNA sequences are present in marine, oxidative, Gram-negative Pseudoalteromonas strains. REP, ERIC and BOX-PCR were used for rapid molecular characterization of both the type species of the genus and environmental strains isolated from samples collected in different geographical areas. PCR-generated genomic fingerprint patterns were found to be both complex and strain specific. Analysis of the genotypic structure of phenotypically diverse P. citrea revealed a geographic clustering of Far Eastern brown-pigmented, agar-digesting strains of this species. Marine isolates of P. nigrifaciens with 67–70% DNA relatedness generated genomic patterns different from those of the type strain and formed a separate cluster. It is concluded that REP, ERIC and BOX-PCR are effective in generating strain specific patterns that can be used to elucidate geographic distribution, with these genomic patterns providing a valuable biogeographic criterion. VL - 25 SN - 0723-2020 ER - TY - CHAP T1 - Combinatorial Algorithms for Design of DNA Arrays T2 - Chip TechnologyChip Technology Y1 - 2002 A1 - Sridhar Hannenhalli A1 - Hubbell, Earl A1 - Lipshutz, Robert A1 - Pevzner, Pavel ED - Hoheisel, Jörg ED - Brazma, A. ED - Büssow, K. ED - Cantor, C. ED - Christians, F. ED - Chui, G. ED - Diaz, R. ED - Drmanac, R. ED - Drmanac, S. ED - Eickhoff, H. ED - Fellenberg, K. ED - Sridhar Hannenhalli ED - Hoheisel, J. ED - Hou, A. ED - Hubbell, E. ED - Jin, H. ED - Jin, P. ED - Jurinke, C. ED - Konthur, Z. ED - Köster, H. ED - Kwon, S. ED - Lacy, S. ED - Lehrach, H. ED - Lipshutz, R. ED - Little, D. ED - Lueking, A. ED - McGall, G. ED - Moeur, B. ED - Nordhoff, E. ED - Nyarsik, L. ED - Pevzner, P. ED - Robinson, A. ED - Sarkans, U. ED - Shafto, J. ED - Sohail, M. ED - Southern, E. ED - Swanson, D. ED - Ukrainczyk, T. ED - van den Boom, D. ED - Vilo, J. ED - Vingron, M. ED - Walter, G. ED - Xu, C. AB - Optimal design of DNA arrays requires the development of algorithms with two-fold goals: reducing the effects caused by unintended illumination ( border length minimization problem ) and reducing the complexity of masks ( mask decomposition problem ). We describe algorithms that reduce the number of rectangles in mask decomposition by 20–30% as compared to a standard array design under the assumption that the arrangement of oligonucleotides on the array is fixed. This algorithm produces provably optimal solution for all studied real instances of array design. We also address the difficult problem of finding an arrangement which minimizes the border length and come up with a new idea of threading that significantly reduces the border length as compared to standard designs. JA - Chip TechnologyChip Technology T3 - Advances in Biochemical Engineering/Biotechnology PB - Springer Berlin / Heidelberg VL - 77 SN - 978-3-540-43215-9 ER - TY - JOUR T1 - Comparative Genome Sequencing for Discovery of Novel Polymorphisms in Bacillus Anthracis JF - ScienceScienceScienceScience Y1 - 2002 A1 - Read, Timothy D. A1 - Salzberg, Steven L. A1 - M. Pop A1 - Shumway, Martin A1 - Umayam, Lowell A1 - Jiang, Lingxia A1 - Holtzapple, Erik A1 - Busch, Joseph D. A1 - Smith, Kimothy L. A1 - Schupp, James M. A1 - Solomon, Daniel A1 - Keim, Paul A1 - Fraser, Claire M. AB - Comparison of the whole-genome sequence ofBacillus anthracis isolated from a victim of a recent bioterrorist anthrax attack with a reference reveals 60 new markers that include single nucleotide polymorphisms (SNPs), inserted or deleted sequences, and tandem repeats. Genome comparison detected four high-quality SNPs between the two sequenced B. anthracischromosomes and seven differences among different preparations of the reference genome. These markers have been tested on a collection of anthrax isolates and were found to divide these samples into distinct families. These results demonstrate that genome-based analysis of microbial pathogens will provide a powerful new tool for investigation of infectious disease outbreaks. VL - 296 SN - 0036-8075, 1095-9203 ER - TY - JOUR T1 - Detection of Cytotoxin-Hemolysin mRNA in Nonculturable Populations of Environmental and Clinical Vibrio Vulnificus Strains in Artificial Seawater JF - Applied and Environmental MicrobiologyAppl. Environ. Microbiol.Applied and Environmental MicrobiologyAppl. Environ. Microbiol. Y1 - 2002 A1 - Fischer-Le Saux, Marion A1 - Hervio-Heath, Dominique A1 - Loaec, Solen A1 - Rita R. Colwell A1 - Pommepuy, Monique AB - The objective of this study was to develop a molecular detection method that better estimates the potential risk associated with the presence of Vibrio vulnificus. For that purpose, we applied seminested reverse transcription-PCR (RT-PCR) to viable but nonculturable (VBNC) populations of V. vulnificus and targeted the cytotoxin-hemolysin virulence gene vvhA. Three strains, two environmental, IF Vv10 and IF Vv18, and one clinical, C7184, were used in this study. Artificial seawater, inoculated with mid-log-phase cells, was maintained at 4°C. VBNC cells resulted after 3, 6, and 14 days for C7184, IF Vv18, and IF Vv10, respectively. Our data indicate that seminested RT-PCR is sensitive for the detection of vvhA mRNA in artificial seawater when exclusively nonculturable bacteria are present. This is the first report of the expression of a toxin gene in VBNC V. vulnificus. Moreover, vvhA transcripts were shown to persist in nonculturable populations over a 4.5-month period, with a progressive decline of the signal over time. This result indicates that special attention should be given to the presence of potentially pathogenic VBNC cells in environmental samples when assessing public health risk. VL - 68 SN - 0099-2240, 1098-5336 ER - TY - JOUR T1 - The draft genome of Ciona intestinalis: insights into chordate and vertebrate origins. JF - Science Y1 - 2002 A1 - Dehal, Paramvir A1 - Satou, Yutaka A1 - Campbell, Robert K A1 - Chapman, Jarrod A1 - Degnan, Bernard A1 - De Tomaso, Anthony A1 - Davidson, Brad A1 - Di Gregorio, Anna A1 - Gelpke, Maarten A1 - Goodstein, David M A1 - Harafuji, Naoe A1 - Hastings, Kenneth E M A1 - Ho, Isaac A1 - Hotta, Kohji A1 - Huang, Wayne A1 - Kawashima, Takeshi A1 - Lemaire, Patrick A1 - Martinez, Diego A1 - Meinertzhagen, Ian A A1 - Necula, Simona A1 - Nonaka, Masaru A1 - Putnam, Nik A1 - Rash, Sam A1 - Saiga, Hidetoshi A1 - Satake, Masanobu A1 - Terry, Astrid A1 - Yamada, Lixy A1 - Wang, Hong-Gang A1 - Awazu, Satoko A1 - Azumi, Kaoru A1 - Boore, Jeffrey A1 - Branno, Margherita A1 - Chin-Bow, Stephen A1 - DeSantis, Rosaria A1 - Doyle, Sharon A1 - Francino, Pilar A1 - Keys, David N A1 - Haga, Shinobu A1 - Hayashi, Hiroko A1 - Hino, Kyosuke A1 - Imai, Kaoru S A1 - Inaba, Kazuo A1 - Kano, Shungo A1 - Kobayashi, Kenji A1 - Kobayashi, Mari A1 - Lee, Byung-In A1 - Makabe, Kazuhiro W A1 - Manohar, Chitra A1 - Matassi, Giorgio A1 - Medina, Monica A1 - Mochizuki, Yasuaki A1 - Mount, Steve A1 - Morishita, Tomomi A1 - Miura, Sachiko A1 - Nakayama, Akie A1 - Nishizaka, Satoko A1 - Nomoto, Hisayo A1 - Ohta, Fumiko A1 - Oishi, Kazuko A1 - Rigoutsos, Isidore A1 - Sano, Masako A1 - Sasaki, Akane A1 - Sasakura, Yasunori A1 - Shoguchi, Eiichi A1 - Shin-i, Tadasu A1 - Spagnuolo, Antoinetta A1 - Stainier, Didier A1 - Suzuki, Miho M A1 - Tassy, Olivier A1 - Takatori, Naohito A1 - Tokuoka, Miki A1 - Yagi, Kasumi A1 - Yoshizaki, Fumiko A1 - Wada, Shuichi A1 - Zhang, Cindy A1 - Hyatt, P Douglas A1 - Larimer, Frank A1 - Detter, Chris A1 - Doggett, Norman A1 - Glavina, Tijana A1 - Hawkins, Trevor A1 - Richardson, Paul A1 - Lucas, Susan A1 - Kohara, Yuji A1 - Levine, Michael A1 - Satoh, Nori A1 - Rokhsar, Daniel S KW - Alleles KW - Animals KW - Apoptosis KW - Base Sequence KW - Cellulose KW - Central Nervous System KW - Ciona intestinalis KW - Computational Biology KW - Endocrine System KW - Gene Dosage KW - Gene Duplication KW - genes KW - Genes, Homeobox KW - Genome KW - Heart KW - Immunity KW - Molecular Sequence Data KW - Multigene Family KW - Muscle Proteins KW - Organizers, Embryonic KW - Phylogeny KW - Polymorphism, Genetic KW - Proteins KW - Sequence Analysis, DNA KW - Sequence Homology, Nucleic Acid KW - Species Specificity KW - Thyroid Gland KW - Urochordata KW - Vertebrates AB -

The first chordates appear in the fossil record at the time of the Cambrian explosion, nearly 550 million years ago. The modern ascidian tadpole represents a plausible approximation to these ancestral chordates. To illuminate the origins of chordate and vertebrates, we generated a draft of the protein-coding portion of the genome of the most studied ascidian, Ciona intestinalis. The Ciona genome contains approximately 16,000 protein-coding genes, similar to the number in other invertebrates, but only half that found in vertebrates. Vertebrate gene families are typically found in simplified form in Ciona, suggesting that ascidians contain the basic ancestral complement of genes involved in cell signaling and development. The ascidian genome has also acquired a number of lineage-specific innovations, including a group of genes engaged in cellulose metabolism that are related to those in bacteria and fungi.

VL - 298 CP - 5601 M3 - 10.1126/science.1080049 ER - TY - JOUR T1 - Effects of Global Climate on Infectious Disease: The Cholera Model JF - Clinical Microbiology ReviewsClin. Microbiol. Rev.Clinical Microbiology ReviewsClin. Microbiol. Rev. Y1 - 2002 A1 - Lipp, Erin K. A1 - Huq, Anwar A1 - Rita R. Colwell AB - Recently, the role of the environment and climate in disease dynamics has become a subject of increasing interest to microbiologists, clinicians, epidemiologists, and ecologists. Much of the interest has been stimulated by the growing problems of antibiotic resistance among pathogens, emergence and/or reemergence of infectious diseases worldwide, the potential of bioterrorism, and the debate concerning climate change. Cholera, caused by Vibrio cholerae, lends itself to analyses of the role of climate in infectious disease, coupled to population dynamics of pathogenic microorganisms, for several reasons. First, the disease has a historical context linking it to specific seasons and biogeographical zones. In addition, the population dynamics of V. cholerae in the environment are strongly controlled by environmental factors, such as water temperature, salinity, and the presence of copepods, which are, in turn, controlled by larger-scale climate variability. In this review, the association between plankton and V. cholerae that has been documented over the last 20 years is discussed in support of the hypothesis that cholera shares properties of a vector-borne disease. In addition, a model for environmental transmission of cholera to humans in the context of climate variability is presented. The cholera model provides a template for future research on climate-sensitive diseases, allowing definition of critical parameters and offering a means of developing more sophisticated methods for prediction of disease outbreaks. VL - 15 SN - 0893-8512, 1098-6618 ER - TY - JOUR T1 - Evidence for a plastid origin of plant ethylene receptor genes. JF - Plant Physiol Y1 - 2002 A1 - Mount, Stephen M A1 - Chang, Caren KW - Amino Acid Sequence KW - Anabaena KW - Arabidopsis KW - Cyanobacteria KW - Molecular Sequence Data KW - Plant Proteins KW - Plastids KW - Protein Kinases KW - Receptors, Cell Surface KW - Sequence Homology, Amino Acid VL - 130 CP - 1 M3 - 10.1104/pp.005397 ER - TY - Generic T1 - Experimental Construction of Very Large Scale DNA Databases with Associative Search T2 - DNA computing: 7th International Workshop on DNA-Based Computers, DNA 7, Tampa, FL, USA, June 10-13, 2001: revised papers Y1 - 2002 A1 - Reif, J. H. A1 - LaBean, T. H. A1 - Pirrung, M. A1 - Rana, V. S. A1 - Guo, B. A1 - Kingsford, Carl A1 - Wickham, G. S. JA - DNA computing: 7th International Workshop on DNA-Based Computers, DNA 7, Tampa, FL, USA, June 10-13, 2001: revised papers VL - 7 ER - TY - CHAP T1 - Fulfilling the promise of marine biotechnology T2 - Marine biotechnology in the twenty-first century: problems, promise, and productsMarine biotechnology in the twenty-first century: problems, promise, and products Y1 - 2002 A1 - Rita R. Colwell ED - National Research Council Committee on Marine Biotechnology: Biomedical Applications of Marine Natural, Products JA - Marine biotechnology in the twenty-first century: problems, promise, and productsMarine biotechnology in the twenty-first century: problems, promise, and products PB - National Academies Press SN - 9780309083423 N1 - (U S. ) ER - TY - JOUR T1 - Genome sequence and comparative analysis of the model rodent malaria parasite Plasmodium yoelii yoelii JF - NatureNature Y1 - 2002 A1 - Carlton, Jane M. A1 - Angiuoli, Samuel V. A1 - Suh, Bernard B. A1 - Kooij, Taco W. A1 - Pertea, Mihaela A1 - Silva, Joana C. A1 - Ermolaeva, Maria D. A1 - Allen, Jonathan E. A1 - J. Selengut A1 - Koo, Hean L. A1 - Peterson, Jeremy D. A1 - M. Pop A1 - Kosack, Daniel S. A1 - Shumway, Martin F. A1 - Bidwell, Shelby L. A1 - Shallom, Shamira J. A1 - Aken, Susan E. van A1 - Riedmuller, Steven B. A1 - Feldblyum, Tamara V. A1 - Cho, Jennifer K. A1 - Quackenbush, John A1 - Sedegah, Martha A1 - Shoaibi, Azadeh A1 - Cummings, Leda M. A1 - Florens, Laurence A1 - Yates, John R. A1 - Raine, J. Dale A1 - Sinden, Robert E. A1 - Harris, Michael A. A1 - Cunningham, Deirdre A. A1 - Preiser, Peter R. A1 - Bergman, Lawrence W. A1 - Vaidya, Akhil B. A1 - Lin, Leo H. van A1 - Janse, Chris J. A1 - Waters, Andrew P. A1 - Smith, Hamilton O. A1 - White, Owen R. A1 - Salzberg, Steven L. A1 - Venter, J. Craig A1 - Fraser, Claire M. A1 - Hoffman, Stephen L. A1 - Gardner, Malcolm J. A1 - Carucci, Daniel J. AB - Species of malaria parasite that infect rodents have long been used as models for malaria disease research. Here we report the whole-genome shotgun sequence of one species, Plasmodium yoelii yoelii, and comparative studies with the genome of the human malaria parasite Plasmodium falciparum clone 3D7. A synteny map of 2,212 P. y. yoelii contiguous DNA sequences (contigs) aligned to 14 P. falciparum chromosomes reveals marked conservation of gene synteny within the body of each chromosome. Of about 5,300 P. falciparum genes, more than 3,300 P. y. yoelii orthologues of predominantly metabolic function were identified. Over 800 copies of a variant antigen gene located in subtelomeric regions were found. This is the first genome sequence of a model eukaryotic parasite, and it provides insight into the use of such systems in the modelling of Plasmodium biology and disease. VL - 419 SN - 0028-0836 ER - TY - JOUR T1 - Genome sequence assembly: Algorithms and issues JF - ComputerComputer Y1 - 2002 A1 - M. Pop A1 - Salzberg, S. L. A1 - Shumway, M. PB - IEEE VL - 35 ER - TY - JOUR T1 - Genome sequence of the human malaria parasite Plasmodium falciparum JF - NatureNature Y1 - 2002 A1 - Gardner, Malcolm J. A1 - Hall, Neil A1 - Fung, Eula A1 - White, Owen A1 - Berriman, Matthew A1 - Hyman, Richard W. A1 - Carlton, Jane M. A1 - Pain, Arnab A1 - Nelson, Karen E. A1 - Bowman, Sharen A1 - Paulsen, Ian T. A1 - James, Keith A1 - Eisen, Jonathan A. A1 - Rutherford, Kim A1 - Salzberg, Steven L. A1 - Craig, Alister A1 - Kyes, Sue A1 - Chan, Man-Suen A1 - Nene, Vishvanath A1 - Shallom, Shamira J. A1 - Suh, Bernard A1 - Peterson, Jeremy A1 - Angiuoli, Sam A1 - Pertea, Mihaela A1 - Allen, Jonathan A1 - J. Selengut A1 - Haft, Daniel A1 - Mather, Michael W. A1 - Vaidya, Akhil B. A1 - Martin, David M. A. A1 - Fairlamb, Alan H. A1 - Fraunholz, Martin J. A1 - Roos, David S. A1 - Ralph, Stuart A. A1 - McFadden, Geoffrey I. A1 - Cummings, Leda M. A1 - Subramanian, G. Mani A1 - Mungall, Chris A1 - Venter, J. Craig A1 - Carucci, Daniel J. A1 - Hoffman, Stephen L. A1 - Newbold, Chris A1 - Davis, Ronald W. A1 - Fraser, Claire M. A1 - Barrell, Bart KW - Animals KW - Chromosome Structures KW - DNA Repair KW - DNA Replication KW - DNA, Protozoan KW - Evolution, Molecular KW - Genome, Protozoan KW - HUMANS KW - Malaria Vaccines KW - Malaria, Falciparum KW - Membrane Transport Proteins KW - Molecular Sequence Data KW - Plasmodium falciparum KW - Plastids KW - Proteome KW - Protozoan Proteins KW - Recombination, Genetic KW - Sequence Analysis, DNA AB - The parasite Plasmodium falciparum is responsible for hundreds of millions of cases of malaria, and kills more than one million African children annually. Here we report an analysis of the genome sequence of P. falciparum clone 3D7. The 23-megabase nuclear genome consists of 14 chromosomes, encodes about 5,300 genes, and is the most (A + T)-rich genome sequenced to date. Genes involved in antigenic variation are concentrated in the subtelomeric regions of the chromosomes. Compared to the genomes of free-living eukaryotic microbes, the genome of this intracellular parasite encodes fewer enzymes and transporters, but a large proportion of genes are devoted to immune evasion and host-parasite interactions. Many nuclear-encoded proteins are targeted to the apicoplast, an organelle involved in fatty-acid and isoprenoid metabolism. The genome sequence provides the foundation for future studies of this organism, and is being exploited in the search for new drugs and vaccines to fight malaria. VL - 419 N1 - http://www.ncbi.nlm.nih.gov/pubmed/12368864?dopt=Abstract ER - TY - JOUR T1 - Genomic profiles of clinical and environmental isolates of Vibrio cholerae O1 in cholera-endemic areas of Bangladesh JF - Proceedings of the National Academy of SciencesProceedings of the National Academy of Sciences Y1 - 2002 A1 - Zo, Y. G. A1 - Rivera, I. N. G. A1 - E. Russek-Cohen A1 - Islam, M. S. A1 - Siddique, A. K. A1 - Yunus, M. A1 - Sack, R. B. A1 - Huq, A. A1 - Rita R. Colwell AB - Diversity, relatedness, and ecological interactions of toxigenic Vibrio cholerae O1 populations in two distinctive habitats, the human intestine and the aquatic environment, were analyzed. Twenty environmental isolates and 42 clinical isolates were selected for study by matching serotype, geographic location of isolation in Bangladesh, and season of isolation. Genetic profiling was done by enterobacterial repetitive intergenic consensus sequence–PCR, optimized for profiling by using the fully sequenced V. cholerae El Tor N16961 genome. Five significant clonal clusters of haplotypes were found from 57 electrophoretic types. Isolates from different areas or habitats intermingled in two of the five significant clusters. Frequencies of haplotypes differed significantly only between the environmental populations (exact test; P < 0.05). Analysis of molecular variance yielded a population genetic structure reflecting the differentiating effects of geographic area, habitat, and sampling time. Although a parameter confounding the latter differences explained 9% of the total molecular variance in the entire population (P < 0.01), the net effect of habitat and time could not be separated because of the small number of environmental isolates included in the study. Five subpopulations from a single area were determined, and from these we were able to estimate a relative differentiating effect of habitat, which was small compared with the effect of temporal change. In conclusion, the resulting population structure supports the hypothesis that spatial and temporal fluctuations in the composition of toxigenic V. cholerae populations in the aquatic environment can cause shifts in the dynamics of the disease. VL - 99 SN - 0027-8424, 1091-6490 ER - TY - JOUR T1 - Identification of non-autonomous non-LTR retrotransposons in the genome of Trypanosoma cruzi JF - Molecular and Biochemical ParasitologyMolecular and Biochemical Parasitology Y1 - 2002 A1 - Bringaud, Frederic A1 - García-Pérez, José Luis A1 - Heras, Sara R. A1 - Ghedin, Elodie A1 - Najib M. El‐Sayed A1 - Andersson, Björn A1 - Baltz, Théo A1 - Lopez, Manuel C. KW - Ingi KW - L1Tc KW - Non-LTR retrotransposon KW - RIME KW - Trypanosoma brucei KW - Trypanosoma cruzi AB - As observed for most eukaryotic cells, trypanosomatids contains non-LTR retrotransposons randomly inserted in the nuclear genome. Autonomous retroelements which, code for their own transposition, have been characterized in Trypanosoma brucei (ingi) and Trypanosoma cruzi (L1Tc), whereas non-autonomous retroelements have only been characterized in T. brucei (RIME). Here, we have characterized in the genome of Trypanosoma cruzi four complete copies of a non-autonomous non-LTR retrotransposon, called NARTc. This 0.26 kb NARTc element has the characteristics of non-LTR retrotransposons: the presence a poly(dA) tail and of a short flanking duplicated motif. Analysis of the Genome Survey Sequence databases indicated that the Trypanosoma cruzi haploid genome contains about 140 NARTc copies and about twice as many L1Tc copies. Interestingly, the NARTc and L1Tc retroelements share, with the Trypanosoma brucei ingi and RIME retrotransposons, a common sequence (the first 45 bp with 91% identity), whereas the remaining sequences are very divergent. This suggests that these four trypanosome non-LTR retrotransposons were derived from the same common ancester and the sequence of their 5'-extremity may have a functional role. In addition, the genome of Leishmania major contains the same conserved motif present in the trypanosome retroelements, whicle no transposable elements have been detected so far in Leishmania sp. VL - 124 SN - 0166-6851 ER - TY - JOUR T1 - Identification of non-autonomous non-LTR retrotransposons in the genome of Trypanosoma cruzi. JF - Mol Biochem Parasitol Y1 - 2002 A1 - Bringaud, Frederic A1 - García-Pérez, José Luis A1 - Heras, Sara R A1 - Ghedin, Elodie A1 - El-Sayed, Najib M A1 - Andersson, Björn A1 - Baltz, Théo A1 - Lopez, Manuel C KW - Animals KW - Base Sequence KW - Computational Biology KW - Genome, Protozoan KW - Long Interspersed Nucleotide Elements KW - Molecular Sequence Data KW - Retroelements KW - Short Interspersed Nucleotide Elements KW - Trypanosoma cruzi AB -

As observed for most eukaryotic cells, trypanosomatids contains non-LTR retrotransposons randomly inserted in the nuclear genome. Autonomous retroelements which, code for their own transposition, have been characterized in Trypanosoma brucei (ingi) and Trypanosoma cruzi (L1Tc), whereas non-autonomous retroelements have only been characterized in T. brucei (RIME). Here, we have characterized in the genome of Trypanosoma cruzi four complete copies of a non-autonomous non-LTR retrotransposon, called NARTc. This 0.26 kb NARTc element has the characteristics of non-LTR retrotransposons: the presence a poly(dA) tail and of a short flanking duplicated motif. Analysis of the Genome Survey Sequence databases indicated that the Trypanosoma cruzi haploid genome contains about 140 NARTc copies and about twice as many L1Tc copies. Interestingly, the NARTc and L1Tc retroelements share, with the Trypanosoma brucei ingi and RIME retrotransposons, a common sequence (the first 45 bp with 91% identity), whereas the remaining sequences are very divergent. This suggests that these four trypanosome non-LTR retrotransposons were derived from the same common ancester and the sequence of their 5'-extremity may have a functional role. In addition, the genome of Leishmania major contains the same conserved motif present in the trypanosome retroelements, whicle no transposable elements have been detected so far in Leishmania sp.

VL - 124 CP - 1-2 ER - TY - JOUR T1 - Identification of transcription factor binding sites in the human genome sequence JF - Mammalian GenomeMammalian Genome Y1 - 2002 A1 - Levy, Samuel A1 - Sridhar Hannenhalli AB - The identification of transcription factor binding sites (TFBS) is an important initial step in determining the DNA signals that regulate transcription of the genome. We tested the performance of three distinct computational methods for the identification of TFBS applied to the human genome sequence, as judged by their ability to recover the location of experimentally determined, and uniquely mapped, TFBS taken from the TRANSFAC database. These identification methods all attempt to filter the quantity of TFBS identified by aligning positional weight matrices that describe the binding site and employ either (i) a P-value threshold for accepting a site, (ii) an over-representation measure of neighboring sites, or (iii) conservation with the mouse genome and application of P-value thresholds. The results show that the best recognition of TFBS is achieved by combining the identification of TFBS in regions of human–mouse conservation and also by applying a high stringency P-value to the TFBS identified in non-coding regions that are not conserved. Additionally, we find that only half of the 481 experimentally mapped sites can be found in sequence regions conserved with mouse, but the predictive power of the binding site identification method is up to threefold higher in the conserved regions. VL - 13 SN - 0938-8990 ER - TY - JOUR T1 - In vitro adhesion to human cells by viable but nonculturable Enterococcus faecalis JF - Current microbiologyCurrent microbiology Y1 - 2002 A1 - Pruzzo, C. A1 - Tarsi, R. A1 - Lleò, M. M. A1 - Signoretto, C. A1 - Zampini, M. A1 - Rita R. Colwell A1 - Canepari, P. AB - The ability of viable but nonculturable (VBNC) Enterococcus faecalis to adhere to Caco-2 and Girardi heart cultured cells and to urinary tract epithelial cells (ECs) was studied. Enterococci were harvested during the vegetative growth phase (early exponential and stationary), in the VBNC state, and after recovery of the ability to divide. VBNC bacteria maintained their adherence capability but the efficiency of attachment was reduced by about 50 to 70%, depending on the target cell employed. The decrease was transient, since enterococci that regained their culturability showed adherence values similar to those observed for actively growing cells. Analysis of the invasive properties of E. faecalis revealed that the VBNC state caused a decrease in the number of bacteria that entered the cultured HEK cells as a result of the reduction in the number of adhering bacteria. These results highlight the importance of studies of the VBNC phenomenon, with respect to both microbial survival in the environment and the impact on human health. VL - 45 ER - TY - JOUR T1 - A new, expressed multigene family containing a hot spot for insertion of retroelements is associated with polymorphic subtelomeric regions of Trypanosoma brucei JF - Eukaryotic cellEukaryotic Cell Y1 - 2002 A1 - Bringaud, F. A1 - Biteau, N. A1 - Melville, S. E. A1 - Hez, S. A1 - Najib M. El‐Sayed A1 - Leech, V. A1 - Berriman, M. A1 - Hall, N. A1 - Donelson, J. E. A1 - Baltz, T. VL - 1 ER - TY - JOUR T1 - A new, expressed multigene family containing a hot spot for insertion of retroelements is associated with polymorphic subtelomeric regions of Trypanosoma brucei. JF - Eukaryot Cell Y1 - 2002 A1 - Bringaud, Frederic A1 - Biteau, Nicolas A1 - Melville, Sara E A1 - Hez, Stéphanie A1 - El-Sayed, Najib M A1 - Leech, Vanessa A1 - Berriman, Matthew A1 - Hall, Neil A1 - Donelson, John E A1 - Baltz, Théo KW - Amino Acid Sequence KW - Animals KW - Base Sequence KW - Cloning, Molecular KW - DNA Primers KW - DNA, Protozoan KW - Escherichia coli KW - Genes, Protozoan KW - Molecular Sequence Data KW - Multigene Family KW - Mutagenesis, Insertional KW - Phylogeny KW - Polymorphism, Genetic KW - Protozoan Proteins KW - Pseudogenes KW - Retroelements KW - sequence alignment KW - Sequence Homology, Amino Acid KW - Telomere KW - Trypanosoma brucei brucei KW - Trypanosoma cruzi AB -

We describe a novel gene family that forms clusters in subtelomeric regions of Trypanosoma brucei chromosomes and partially accounts for the observed clustering of retrotransposons. The ingi and ribosomal inserted mobile element (RIME) non-LTR retrotransposons share 250 bp at both extremities and are the most abundant putatively mobile elements, with about 500 copies per haploid genome. From cDNA clones and subsequently in the T. brucei genomic DNA databases, we identified 52 homologous gene and pseudogene sequences, 16 of which contain a RIME and/or ingi retrotransposon inserted at exactly the same relative position. Here these genes are called the RHS family, for retrotransposon hot spot. Comparison of the protein sequences encoded by RHS genes (21 copies) and pseudogenes (24 copies) revealed a conserved central region containing an ATP/GTP-binding motif and the RIME/ingi insertion site. The RHS proteins share between 13 and 96% identity, and six subfamilies, RHS1 to RHS6, can be defined on the basis of their divergent C-terminal domains. Immunofluorescence and Western blot analyses using RHS subfamily-specific immune sera show that RHS proteins are constitutively expressed and occur mainly in the nucleus. Analysis of Genome Survey Sequence databases indicated that the Trypanosoma brucei diploid genome contains about 280 RHS (pseudo)genes. Among the 52 identified RHS (pseudo)genes, 48 copies are in three RHS clusters located in subtelomeric regions of chromosomes Ia and II and adjacent to the active bloodstream form expression site in T. brucei strain TREU927/4 GUTat10.1. RHS genes comprise the remaining sequence of the size-polymorphic "repetitive region" described for T. brucei chromosome I, and a homologous gene family is present in the Trypanosoma cruzi genome.

VL - 1 CP - 1 ER - TY - JOUR T1 - Phylogenetic analysis based on 18S ribosomal RNA gene sequences supports the existence of class Polyacanthocephala (Acanthocephala) JF - Mol Phylogenet EvolMol Phylogenet Evol Y1 - 2002 A1 - García-Varela, M. A1 - Michael P. Cummings A1 - Pérez-Ponce de León, G. A1 - Gardner, S. L. A1 - Laclette, J. P. AB - Members of phylum Acanthocephala are parasites of vertebrates and arthropods and are distributed worldwide. The phylum has traditionally been divided into three classes, Archiacanthocephala, Palaeacanthocephala, and Eoacanthocephala; a fourth class, Polyacanthocephala, has been recently proposed. However, erection of this new class, based on morphological characters, has been controversial. We sequenced the near complete 18S rRNA gene of Polyacanthorhynchus caballeroi (Polyacanthocephala) and Rhadinorhynchus sp. (Palaeacanthocephala); these sequences were aligned with another 21 sequences of acanthocephalans representing the three widely recognized classes of the phylum and with 16 sequences from outgroup taxa. Phylogenetic relationships inferred by maximum-likelihood and maximum-parsimony analyses showed Archiacanthocephala as the most basal group within the phylum, whereas classes Polyacanthocephala + Eoacanthocephala formed a monophyletic clade, with Palaeacanthocephala as its sister group. These results are consistent with the view of Polyacanthocephala representing an independent class within Acanthocephala. VL - 23 ER - TY - JOUR T1 - Predicting Transcription Factor Synergism JF - Nucleic Acids ResearchNucl. Acids Res.Nucleic Acids ResearchNucl. Acids Res. Y1 - 2002 A1 - Sridhar Hannenhalli A1 - Levy, Samuel AB - Transcriptional regulation is mediated by a battery of transcription factor (TF) proteins, that form complexes involving protein–protein and protein–DNA interactions. Individual TFs bind to their cognate cis‐elements or transcription factor‐binding sites (TFBS). TFBS are organized on the DNA proximal to the gene in groups confined to a few hundred base pair regions. These groups are referred to as modules. Various modules work together to provide the combinatorial regulation of gene transcription in response to various developmental and environmental conditions. The sets of modules constitute a promoter model. Determining the TFs that preferentially work in concert as part of a module is an essential component of understanding transcriptional regulation. The TFs that act synergistically in such a fashion are likely to have their cis‐elements co‐localized on the genome at specific distances apart. We exploit this notion to predict TF pairs that are likely to be part of a transcriptional module on the human genome sequence. The computational method is validated statistically, using known interacting pairs extracted from the literature. There are 251 TFBS pairs up to 50 bp apart and 70 TFBS pairs up to 200 bp apart that score higher than any of the known synergistic pairs. Further investigation of 50 pairs randomly selected from each of these two sets using PubMed queries provided additional supporting evidence from the existing biological literature suggesting TF synergism for these novel pairs. VL - 30 SN - 0305-1048, 1362-4962 ER - TY - JOUR T1 - Proceedings of the sixth annual international conference on Computational biology Y1 - 2002 A1 - Myers, G. A1 - Sridhar Hannenhalli A1 - Sankoff, D. A1 - Istrail, S. A1 - Pevzner, P. A1 - Waterman, M. PB - ACM ER - TY - JOUR T1 - Purification and properties of the extracellular lipase, LipA, of Acinetobacter sp. RAG‐1 JF - European Journal of BiochemistryEuropean Journal of Biochemistry Y1 - 2002 A1 - Snellman, Erick A. A1 - Sullivan, Elise R. A1 - Rita R. Colwell KW - Acinetobacter sp. RAG‐1 KW - LipA KW - lipase KW - protein purification KW - zymogram AB - An extracellular lipase, LipA, extracted from Acinetobacter sp. RAG-1 grown on hexadecane was purified and properties of the enzyme investigated. The enzyme is released into the growth medium during the transition to stationary phase. The lipase was harvested from cells grown to stationary phase, and purified with 22% yield and > 10-fold purification. The protein demonstrates little affinity for anion exchange resins, with contaminating proteins removed by passing crude supernatants over a Mono Q column. The lipase was bound to a butyl Sepharose column and eluted in a Triton X-100 gradient. The molecular mass (33 kDa) was determined employing SDS/PAGE. LipA was found to be stable at pH 5.8–9.0, with optimal activity at 9.0. The lipase remained active at temperatures up to 70 °C, with maximal activity observed at 55 °C. LipA is active against a wide range of fatty acid esters of p-nitrophenyl, but preferentially attacks medium length acyl chains (C6, C8). The enzyme demonstrates hydrolytic activity in emulsions of both medium and long chain triglycerides, as demonstrated by zymogram analysis. RAG-1 lipase is stabilized by Ca2+, with no loss in activity observed in preparations containing the cation, compared to a 70% loss over 30 h without Ca2+. The lipase is strongly inhibited by EDTA, Hg2+, and Cu2+, but shows no loss in activity after incubation with other metals or inhibitors examined in this study. The protein retains more than 75% of its initial activity after exposure to organic solvents, but is rapidly deactivated by pyridine. RAG-1 lipase offers potential for use as a biocatalyst. VL - 269 SN - 1432-1033 ER - TY - JOUR T1 - Sequence of Plasmodium falciparum chromosomes 2, 10, 11 and 14 JF - NatureNature Y1 - 2002 A1 - Gardner, Malcolm J. A1 - Shallom, Shamira J. A1 - Carlton, Jane M. A1 - Salzberg, Steven L. A1 - Nene, Vishvanath A1 - Shoaibi, Azadeh A1 - Ciecko, Anne A1 - Lynn, Jeffery A1 - Rizzo, Michael A1 - Weaver, Bruce A1 - Jarrahi, Behnam A1 - Brenner, Michael A1 - Parvizi, Babak A1 - Tallon, Luke A1 - Moazzez, Azita A1 - Granger, David A1 - Fujii, Claire A1 - Hansen, Cheryl A1 - Pederson, James A1 - Feldblyum, Tamara A1 - Peterson, Jeremy A1 - Suh, Bernard A1 - Angiuoli, Sam A1 - Pertea, Mihaela A1 - Allen, Jonathan A1 - J. Selengut A1 - White, Owen A1 - Cummings, Leda M. A1 - Smith, Hamilton O. A1 - Adams, Mark D. A1 - Venter, J. Craig A1 - Carucci, Daniel J. A1 - Hoffman, Stephen L. A1 - Fraser, Claire M. KW - Animals KW - Chromosomes KW - DNA, Protozoan KW - Genome, Protozoan KW - Plasmodium falciparum KW - Proteome KW - Protozoan Proteins KW - Sequence Analysis, DNA AB - The mosquito-borne malaria parasite Plasmodium falciparum kills an estimated 0.7-2.7 million people every year, primarily children in sub-Saharan Africa. Without effective interventions, a variety of factors-including the spread of parasites resistant to antimalarial drugs and the increasing insecticide resistance of mosquitoes-may cause the number of malaria cases to double over the next two decades. To stimulate basic research and facilitate the development of new drugs and vaccines, the genome of Plasmodium falciparum clone 3D7 has been sequenced using a chromosome-by-chromosome shotgun strategy. We report here the nucleotide sequences of chromosomes 10, 11 and 14, and a re-analysis of the chromosome 2 sequence. These chromosomes represent about 35% of the 23-megabase P. falciparum genome. VL - 419 N1 - http://www.ncbi.nlm.nih.gov/pubmed/12368868?dopt=Abstract ER - TY - Generic T1 - Sequencing the human genome T2 - Proceedings of the sixth annual international conference on Computational biology Y1 - 2002 A1 - Venter, J. C. JA - Proceedings of the sixth annual international conference on Computational biology PB - ACM ER - TY - JOUR T1 - Simple Procedure for Rapid Identification of Vibrio Cholerae from the Aquatic Environment JF - Applied and Environmental MicrobiologyAppl. Environ. Microbiol.Applied and Environmental MicrobiologyAppl. Environ. Microbiol. Y1 - 2002 A1 - Choopun, Nipa A1 - Louis, Valérie A1 - Huq, Anwar A1 - Rita R. Colwell AB - Biochemical tests commonly used to screen for Vibrio cholerae in environmental samples were evaluated, and we found that a combination of alkaline peptone enrichment followed by streaking on thiosulfate citrate bile salts sucrose agar and testing for arginine dihydrolase activity and esculin hydrolysis was an effective rapid technique to screen for aquatic environmental V. cholerae. This technique provided 100% sensitivity and ≥70% specificity. VL - 68 SN - 0099-2240, 1098-5336 ER - TY - JOUR T1 - Trypanosoma cruzi: RNA structure and post-transcriptional control of tubulin gene expression JF - Experimental ParasitologyExperimental Parasitology Y1 - 2002 A1 - Bartholomeu, Daniella C. A1 - Silva, Rosiane A. A1 - Galvão, Lucia M. C. A1 - Najib M. El‐Sayed A1 - Donelson, John E. A1 - Teixeira, Santuza M. R. AB - Changes in tubulin expression are among the biochemical and morphological adaptations that occur during the life cycle of Trypanosomatids. To investigate the mechanism responsible for the differential accumulation of tubulin mRNAs in Trypanosoma cruzi, we determine the sequences of [alpha]- and [beta]-tubulin transcripts and analyzed their expression during the life cycle of the parasite. Two [beta]-tubulin mRNAs of 1.9 and 2.3 kb were found to differ mainly by an additional 369 nucleotides at the end of the 3' untranslated region (UTR). Although their transcription rates are similar in epimastigotes and amastigotes, [alpha]- and [beta]-tubulin transcripts are 3- to 6-fold more abundant in epimastigotes than in trypomastigotes and amastigotes. Accordingly, the half-lives of [alpha]- and [beta]-tubulin mRNAs are significantly higher in epimastigotes than in amastigotes. Transient transfection experiments indicated that positive regulatory elements occur in the 3' UTR plus downstream intergenic region of the [alpha]-tubulin gene and that both positive and negative elements occur in the equivalent regions of the [beta]-tubulin gene.Index Descriptions and Abbreviations: Kinetoplastida; Trypanosoma cruzi; tubulin; gene regulation; PCR, polymerase chain reaction; UTR, untranslated region; IR, intergenic region; SL, spliced leader; BAC, bacterial artificial chromosome. VL - 102 SN - 0014-4894 ER - TY - JOUR T1 - Trypanosoma cruzi: RNA structure and post-transcriptional control of tubulin gene expression. JF - Exp Parasitol Y1 - 2002 A1 - Bartholomeu, Daniella C A1 - Silva, Rosiane A A1 - Galvão, Lucia M C A1 - el-Sayed, Najib M A A1 - Donelson, John E A1 - Teixeira, Santuza M R KW - Animals KW - Base Sequence KW - Blotting, Northern KW - DNA, Complementary KW - DNA, Protozoan KW - Gene Expression Regulation KW - Half-Life KW - Life Cycle Stages KW - Molecular Sequence Data KW - RNA Processing, Post-Transcriptional KW - RNA, Messenger KW - RNA, Protozoan KW - Transcription, Genetic KW - Transfection KW - Trypanosoma cruzi KW - Tubulin AB -

Changes in tubulin expression are among the biochemical and morphological adaptations that occur during the life cycle of Trypanosomatids. To investigate the mechanism responsible for the differential accumulation of tubulin mRNAs in Trypanosoma cruzi, we determine the sequences of alpha- and beta-tubulin transcripts and analyzed their expression during the life cycle of the parasite. Two beta-tubulin mRNAs of 1.9 and 2.3 kb were found to differ mainly by an additional 369 nucleotides at the end of the 3' untranslated region (UTR). Although their transcription rates are similar in epimastigotes and amastigotes, alpha- and beta-tubulin transcripts are 3- to 6-fold more abundant in epimastigotes than in trypomastigotes and amastigotes. Accordingly, the half-lives of alpha- and beta-tubulin mRNAs are significantly higher in epimastigotes than in amastigotes. Transient transfection experiments indicated that positive regulatory elements occur in the 3' UTR plus downstream intergenic region of the alpha-tubulin gene and that both positive and negative elements occur in the equivalent regions of the beta-tubulin gene.

VL - 102 CP - 3-4 ER - TY - JOUR T1 - A voyage of discovery: cholera, climate and complexity JF - Environmental MicrobiologyEnvironmental Microbiology Y1 - 2002 A1 - Rita R. Colwell VL - 4 SN - 1462-2920 ER - TY - JOUR T1 - Analysis and prediction of protein functional sub-types from protein sequence alignments Y1 - 2001 A1 - Sridhar Hannenhalli A1 - Russell, R. B. N1 - EP Patent 1,096,411 ER - TY - JOUR T1 - Analysis of a donor gene region for a variant surface glycoprotein and its expression site in African trypanosomes JF - Nucleic acids researchNucleic Acids Research Y1 - 2001 A1 - LaCount, D. J. A1 - Najib M. El‐Sayed A1 - Kaul, S. A1 - Wanless, D. A1 - Turner, C. M. R. A1 - Donelson, J. E. VL - 29 ER - TY - CONF T1 - Automatically tracking and analyzing the behavior of live insect colonies T2 - the fifth international conferenceProceedings of the fifth international conference on Autonomous agents - AGENTS '01 Y1 - 2001 A1 - Balch, Tucker A1 - Khan, Zia A1 - Veloso, Manuela JA - the fifth international conferenceProceedings of the fifth international conference on Autonomous agents - AGENTS '01 PB - ACM Press CY - Montreal, Quebec, CanadaNew York, New York, USA SN - 158113326X UR - http://portal.acm.org/citation.cfm?doid=375735http://portal.acm.org/citation.cfm?doid=375735.376434 M3 - 10.1145/37573510.1145/375735.376434 ER - TY - JOUR T1 - Cortical Spreading depression and the pathogenesis of brain disorders: a computational and neural network-based investigation JF - Neurological researchNeurological research Y1 - 2001 A1 - Ruppin, E. A1 - Reggia, James A. VL - 23 ER - TY - Generic T1 - Efficient perspective-accurate silhouette computation and applications T2 - Proceedings of the seventeenth annual symposium on Computational geometry Y1 - 2001 A1 - M. Pop A1 - Duncan, Christian A1 - Barequet, Gill A1 - Goodrich, Michael A1 - Huang, Wenjing A1 - Kumar, Subodh KW - rendering KW - silhouette KW - simplification AB - Silhouettes are perceptually and geometrically salient features of geo metric models. Hence a number of graphics and visualization applications need to find them to aid further processing. The efficient computation of silhouettes, especially in the context of perspective projection, is known to be difficult. This paper presents a novel efficient and practical algorithm to compute silhouettes from a sequence of viewpoints under perspective projection. Parallel projection is a special case of this algorithm. Our approach is based on a point-plane duality in three dimensions, which allows an efficient computation of the \emph{changes} in the silhouette of a polygonal model between consecutive frames. In addition, we present several applications of our technique to problems from computer graphics and medical visualization. We also provide experimental data that show the efficiency of our approach. million vertices on an SGI Onyx workstation. JA - Proceedings of the seventeenth annual symposium on Computational geometry T3 - SCG '01 PB - ACM CY - New York, NY, USA SN - 1-58113-357-X ER - TY - JOUR T1 - Enrichment of Regulatory Signals in Conserved Non-Coding Genomic Sequence JF - BioinformaticsBioinformaticsBioinformaticsBioinformatics Y1 - 2001 A1 - Levy, Samuel A1 - Sridhar Hannenhalli A1 - Workman, Christopher AB - Motivation: Whole genome shotgun sequencing strategies generate sequence data prior to the application of assembly methodologies that result in contiguous sequence. Sequence reads can be employed to indicate regions of conservation between closely related species for which only one genome has been assembled. Consequently, by using pairwise sequence alignments methods it is possible to identify novel, non-repetitive, conserved segments in non-coding sequence that exist between the assembled human genome and mouse whole genome shotgun sequencing fragments. Conserved non-coding regions identify potentially functional DNA that could be involved in transcriptional regulation.Results: Local sequence alignment methods were applied employing mouse fragments and the assembled human genome. In addition, transcription factor binding sites were detected by aligning their corresponding positional weight matrices to the sequence regions. These methods were applied to a set of transcripts corresponding to 502 genes associated with a variety of different human diseases taken from the Online Mendelian Inheritance in Man database. Using statistical arguments we have shown that conserved non-coding segments contain an enrichment of transcription factor binding sites when compared to the sequence background in which the conserved segments are located. This enrichment of binding sites was not observed in coding sequence. Conserved non-coding segments are not extensively repeated in the genome and therefore their identification provides a rapid means of finding genes with related conserved regions, and consequently potentially related regulatory mechanism. Conserved segments in upstream regions are found to contain binding sites that are co-localized in a manner consistent with experimentally known transcription factor pairwise co-occurrences and afford the identification of novel co-occurring Transcription Factor (TF) pairs. This study provides a methodology and more evidence to suggest that conserved non-coding regions are biologically significant since they contain a statistical enrichment of regulatory signals and pairs of signals that enable the construction of regulatory models for human genes. Contact: samuel.levy@celera.com VL - 17 SN - 1367-4803, 1460-2059 ER - TY - JOUR T1 - MDP-1 is a new and distinct member of the haloacid dehalogenase family of aspartate-dependent phosphohydrolases JF - BiochemistryBiochemistry Y1 - 2001 A1 - J. Selengut KW - Amino Acid Motifs KW - Amino Acid Sequence KW - Animals KW - Aspartic Acid KW - Catalytic Domain KW - HUMANS KW - Hydrolases KW - Mice KW - Molecular Sequence Data KW - Multigene Family KW - Mutagenesis, Site-Directed KW - Phosphoprotein Phosphatases KW - Protein Structure, Tertiary KW - Protein Tyrosine Phosphatases KW - Rats KW - Saccharomyces cerevisiae KW - sequence alignment KW - Sequence Homology, Amino Acid AB - MDP-1 is a eukaryotic magnesium-dependent acid phosphatase with little sequence homology to previously characterized phosphatases. The presence of a conserved motif (Asp-X-Asp-X-Thr) in the N terminus of MDP-1 suggested a relationship to the haloacid dehalogenase (HAD) superfamily, which contains a number of magnesium-dependent acid phosphatases. These phosphatases utilize an aspartate nucleophile and contain a number of conserved active-site residues and hydrophobic patches, which can be plausibly aligned with conserved residues in MDP-1. Seven site-specific point mutants of MDP-1 were produced by modifying the catalytic aspartate, serine, and lysine residues to asparagine or glutamate, alanine, and arginine, respectively. The activity of these mutants confirms the assignment of MDP-1 as a member of the HAD superfamily. Detailed comparison of the sequence of the 15 MDP-1 sequences from various organisms with other HAD superfamily sequences suggests that MDP-1 is not closely related to any particular member of the superfamily. The crystal structures of several HAD family enzymes identify a domain proximal to the active site responsible for important interactions with low molecular weight substrates. The absence of this domain or any other that might perform the same function in MDP-1 suggests an "open" active site capable of interactions with large substrates such as proteins. This suggestion was experimentally confirmed by demonstration that MDP-1 is competent to catalyze the dephosphorylation of tyrosine-phosphorylated proteins. VL - 40 N1 - http://www.ncbi.nlm.nih.gov/pubmed/11601995?dopt=Abstract ER - TY - JOUR T1 - Promoter prediction in the human genome JF - BioinformaticsBioinformatics Y1 - 2001 A1 - Sridhar Hannenhalli A1 - Levy, S. AB - Computational prediction of eukaryotic polII promoters has been one of the most elusive problems despite considerable effort devoted to the study. Researchers have looked for various types of signals around the transcriptional start site (TSS), viz. oligo-nucleotide statistics, potential binding sites for core factors, clusters of binding sites, proximity to CpG islands etc.. The proximity of CpG islands to gene starts is now a well established fact, although until recently, it was based on very little genomic data. In this work we explore the possibility of enhancing the promoter prediction accuracy by combining CpG island information with a few other, biologically motivated, seemingly independent signals, that cover most of the known knowledge. We benchmarked the method on a much larger genomic datasets compared to previous studies. We were able to improve slightly upon current prediction accuracy. Furthermore, we observe that CpG islands are the most dominant signals and the other signals do not improve the prediction. This suggests that the computational prediction of promoters for genes with no associated CpG-island (typically having tissue-specific expression) looking only at the immediate neighborhood of the TSS may not even be possible. We suggest some biological experiments and studies to better understand the biology of transcription. VL - 17 SN - 1367-4803, 1460-2059 ER - TY - JOUR T1 - Relating amino acid sequence to phenotype: analysis of peptide-binding data JF - BiometricsBiometrics Y1 - 2001 A1 - Segal, M. R. A1 - Michael P. Cummings A1 - Hubbard, A. E. AB - We illustrate data analytic concerns that arise in the context of relating genotype, as represented by amino acid sequence, to phenotypes (outcomes). The present application examines whether peptides that bind to a particular major histocompatibility complex (MHC) class I molecule have characteristic amino acid sequences. However, the concerns identified and addressed are considerably more general. It is recognized that simple rules for predicting binding based solely on preferences for specific amino acids in certain (anchor) positions of the peptide's amino acid sequence are generally inadequate and that binding is potentially influenced by all sequence positions as well as between-position interactions. The desire to elucidate these more complex prediction rules has spawned various modeling attempts, the shortcomings of which provide motivation for the methods adopted here. Because of (i) this need to model between-position interactions, (ii) amino acids constituting a highly (20) multilevel unordered categorical covariate, and (iii) there frequently being numerous such covariates (i.e., positions) comprising the sequence, standard regression/classification techniques are problematic due to the proliferation of indicator variables required for encoding the sequence position covariates and attendant interactions. These difficulties have led to analyses based on (continuous) properties (e.g., molecular weights) of the amino acids. However, there is potential information loss in such an approach if the properties used are incomplete and/or do not capture the mechanism underlying association with the phenotype. Here we demonstrate that handling unordered categorical covariates with numerous levels and accompanying interactions can be done effectively using classification trees and recently devised bump-hunting methods. We further tackle the question of whether observed associations are attributable to amino acid properties as well as addressing the assessment and implications of between-position covariation. VL - 57 ER - TY - JOUR T1 - The African trypanosome genome JF - International Journal for ParasitologyInternational Journal for Parasitology Y1 - 2000 A1 - Najib M. El‐Sayed A1 - Hegde, Priti A1 - Quackenbush, John A1 - Melville, Sara E. A1 - Donelson, John E. AB - The haploid nuclear genome of the African trypanosome, Trypanosoma brucei, is about 35 Mb and varies in size among different trypanosome isolates by as much as 25%. The nuclear DNA of this diploid organism is distributed among three size classes of chromosomes: the megabase chromosomes of which there are at least 11 pairs ranging from 1 Mb to more than 6 Mb (numbered I-XI from smallest to largest); several intermediate chromosomes of 200-900 kb and uncertain ploidy; and about 100 linear minichromosomes of 50-150 kb. Size differences of as much as four-fold can occur, both between the two homologues of a megabase chromosome pair in a specific trypanosome isolate and among chromosome pairs in different isolates. The genomic DNA sequences determined to date indicated that about 50% of the genome is coding sequence. The chromosomal telomeres possess TTAGGG repeats and many, if not all, of the telomeres of the megabase and intermediate chromosomes are linked to expression sites for genes encoding variant surface glycoproteins (VSGs). The minichromosomes serve as repositories for VSG genes since some but not all of their telomeres are linked to unexpressed VSG genes. A gene discovery program, based on sequencing the ends of cloned genomic DNA fragments, has generated more than 20 Mb of discontinuous single-pass genomic sequence data during the past year, and the complete sequences of chromosomes I and II (about 1 Mb each) in T. brucei GUTat 10.1 are currently being determined. It is anticipated that the entire genomic sequence of this organism will be known in a few years. Analysis of a test microarray of 400 cDNAs and small random genomic DNA fragments probed with RNAs from two developmental stages of T. brucei demonstrates that the microarray technology can be used to identify batteries of genes differentially expressed during the various life cycle stages of this parasite. VL - 30 SN - 0020-7519 ER - TY - JOUR T1 - Analysis and prediction of functional sub-types from protein sequence alignments JF - Journal of Molecular BiologyJournal of Molecular Biology Y1 - 2000 A1 - Sridhar Hannenhalli A1 - Russell, Robert B. KW - prediction KW - protein function KW - protein structure KW - sequence alignment AB - The increasing number and diversity of protein sequence families requires new methods to define and predict details regarding function. Here, we present a method for analysis and prediction of functional sub-types from multiple protein sequence alignments. Given an alignment and set of proteins grouped into sub-types according to some definition of function, such as enzymatic specificity, the method identifies positions that are indicative of functional differences by comparison of sub-type specific sequence profiles, and analysis of positional entropy in the alignment. Alignment positions with significantly high positional relative entropy correlate with those known to be involved in defining sub-types for nucleotidyl cyclases, protein kinases, lactate/malate dehydrogenases and trypsin-like serine proteases. We highlight new positions for these proteins that suggest additional experiments to elucidate the basis of specificity. The method is also able to predict sub-type for unclassified sequences. We assess several variations on a prediction method, and compare them to simple sequence comparisons. For assessment, we remove close homologues to the sequence for which a prediction is to be made (by a sequence identity above a threshold). This simulates situations where a protein is known to belong to a protein family, but is not a close relative of another protein of known sub-type. Considering the four families above, and a sequence identity threshold of 30 %, our best method gives an accuracy of 96 % compared to 80 % obtained for sequence similarity and 74 % for BLAST. We describe the derivation of a set of sub-type groupings derived from an automated parsing of alignments from PFAM and the SWISSPROT database, and use this to perform a large-scale assessment. The best method gives an average accuracy of 94 % compared to 68 % for sequence similarity and 79 % for BLAST. We discuss implications for experimental design, genome annotation and the prediction of protein function and protein intra-residue distances. VL - 303 SN - 0022-2836 ER - TY - JOUR T1 - Carbonic anhydrase III: the phosphatase activity is extrinsic JF - Archives of biochemistry and biophysicsArchives of biochemistry and biophysics Y1 - 2000 A1 - Kim, G. A1 - J. Selengut A1 - Levine, R. L. KW - Animals KW - Carbonic Anhydrases KW - Chromatography, High Pressure Liquid KW - Cloning, Molecular KW - Enzyme Activation KW - Glutathione KW - Kinetics KW - Liver KW - Male KW - Muscles KW - Phosphoric Monoester Hydrolases KW - Precipitin Tests KW - Rabbits KW - Rats KW - Rats, Inbred F344 KW - Recombinant Proteins KW - Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization KW - Time factors AB - The carbonic anhydrases reversibly hydrate carbon dioxide to yield bicarbonate and hydrogen ion. They have a variety of physiological functions, although the specific roles of each of the 10 known isozymes are unclear. Carbonic anhydrase isozyme III is particularly rich in skeletal muscle and adipocytes, and it is unique among the isozymes in also exhibiting phosphatase activity. Previously published studies provided evidence that the phosphatase activity was intrinsic to carbonic anhydrase III, that it had specificity for tyrosine phosphate, and that activity was regulated by reversible glutathionylation of cysteine186. To study the mechanism of this phosphatase, we cloned and expressed the rat liver carbonic anhydrase III. The purified recombinant had the same specific activity as the carbonic anhydrase purified from rat liver, but it had virtually no phosphatase activity. We attempted to identify an activator of the phosphatase in rat liver and found a protein of approximately 14 kDa, the amount of which correlated with the phosphatase activity of the carbonic anhydrase III fractions. It was identified as liver fatty acid binding protein, which was then purified to test for activity as an activator of the phosphatase and for protein-protein interaction, but neither binding nor activation could be demonstrated. Immunoprecipitation experiments established that carbonic anhydrase III could be separated from the phosphatase activity. Finally, adding additional purification steps completely separated the phosphatase activity from the carbonic anhydrase activity. We conclude that the phosphatase activity previously considered to be intrinsic to carbonic anhydrase III is actually extrinsic. Thus, this isozyme exhibits only the carbon dioxide hydratase and esterase activities characteristic of the other mammalian isozymes, and the phosphatase previously shown to be activated by glutathionylation is not carbonic anhydrase III. VL - 377 N1 - http://www.ncbi.nlm.nih.gov/pubmed/10845711?dopt=Abstract ER - TY - JOUR T1 - A Case for Evolutionary Genomics and the Comprehensive Examination of Sequence Biodiversity JF - Molecular Biology and EvolutionMol Biol EvolMolecular Biology and EvolutionMol Biol Evol Y1 - 2000 A1 - Pollock, David D. A1 - Eisen, Jonathan A. A1 - Doggett, Norman A. A1 - Michael P. Cummings AB - Comparative analysis is one of the most powerful methods available for understanding the diverse and complex systems found in biology, but it is often limited by a lack of comprehensive taxonomic sampling. Despite the recent development of powerful genome technologies capable of producing sequence data in large quantities (witness the recently completed first draft of the human genome), there has been relatively little change in how evolutionary studies are conducted. The application of genomic methods to evolutionary biology is a challenge, in part because gene segments from different organisms are manipulated separately, requiring individual purification, cloning, and sequencing. We suggest that a feasible approach to collecting genome-scale data sets for evolutionary biology (i.e., evolutionary genomics) may consist of combination of DNA samples prior to cloning and sequencing, followed by computational reconstruction of the original sequences. This approach will allow the full benefit of automated protocols developed by genome projects to be realized; taxon sampling levels can easily increase to thousands for targeted genomes and genomic regions. Sequence diversity at this level will dramatically improve the quality and accuracy of phylogenetic inference, as well as the accuracy and resolution of comparative evolutionary studies. In particular, it will be possible to make accurate estimates of normal evolution in the context of constant structural and functional constraints (i.e., site-specific substitution probabilities), along with accurate estimates of changes in evolutionary patterns, including pairwise coevolution between sites, adaptive bursts, and changes in selective constraints. These estimates can then be used to understand and predict the effects of protein structure and function on sequence evolution and to predict unknown details of protein structure, function, and functional divergence. In order to demonstrate the practicality of these ideas and the potential benefit for functional genomic analysis, we describe a pilot project we are conducting to simultaneously sequence large numbers of vertebrate mitochondrial genomes. VL - 17 SN - 0737-4038, 1537-1719 ER - TY - JOUR T1 - Expanding the definition of informational suppression. JF - Trends Genet Y1 - 2000 A1 - Mount, S M A1 - Anderson, P KW - Animals KW - DNA-Binding Proteins KW - Drosophila Proteins KW - Nuclear Proteins KW - Recombinant Proteins KW - Repressor Proteins KW - Suppression, Genetic KW - Transcription Factors VL - 16 CP - 4 ER - TY - JOUR T1 - Exploiting coherence in spatial database queries Y1 - 2000 A1 - M. Pop A1 - Adviser-Kosaraju, S. R. PB - The Johns Hopkins University ER - TY - JOUR T1 - The genome sequence of Drosophila melanogaster. JF - Science Y1 - 2000 A1 - Adams, M D A1 - Celniker, S E A1 - Holt, R A A1 - Evans, C A A1 - Gocayne, J D A1 - Amanatides, P G A1 - Scherer, S E A1 - Li, P W A1 - Hoskins, R A A1 - Galle, R F A1 - George, R A A1 - Lewis, S E A1 - Richards, S A1 - Ashburner, M A1 - Henderson, S N A1 - Sutton, G G A1 - Wortman, J R A1 - Yandell, M D A1 - Zhang, Q A1 - Chen, L X A1 - Brandon, R C A1 - Rogers, Y H A1 - Blazej, R G A1 - Champe, M A1 - Pfeiffer, B D A1 - Wan, K H A1 - Doyle, C A1 - Baxter, E G A1 - Helt, G A1 - Nelson, C R A1 - Gabor, G L A1 - Abril, J F A1 - Agbayani, A A1 - An, H J A1 - Andrews-Pfannkoch, C A1 - Baldwin, D A1 - Ballew, R M A1 - Basu, A A1 - Baxendale, J A1 - Bayraktaroglu, L A1 - Beasley, E M A1 - Beeson, K Y A1 - Benos, P V A1 - Berman, B P A1 - Bhandari, D A1 - Bolshakov, S A1 - Borkova, D A1 - Botchan, M R A1 - Bouck, J A1 - Brokstein, P A1 - Brottier, P A1 - Burtis, K C A1 - Busam, D A A1 - Butler, H A1 - Cadieu, E A1 - Center, A A1 - Chandra, I A1 - Cherry, J M A1 - Cawley, S A1 - Dahlke, C A1 - Davenport, L B A1 - Davies, P A1 - de Pablos, B A1 - Delcher, A A1 - Deng, Z A1 - Mays, A D A1 - Dew, I A1 - Dietz, S M A1 - Dodson, K A1 - Doup, L E A1 - Downes, M A1 - Dugan-Rocha, S A1 - Dunkov, B C A1 - Dunn, P A1 - Durbin, K J A1 - Evangelista, C C A1 - Ferraz, C A1 - Ferriera, S A1 - Fleischmann, W A1 - Fosler, C A1 - Gabrielian, A E A1 - Garg, N S A1 - Gelbart, W M A1 - Glasser, K A1 - Glodek, A A1 - Gong, F A1 - Gorrell, J H A1 - Gu, Z A1 - Guan, P A1 - Harris, M A1 - Harris, N L A1 - Harvey, D A1 - Heiman, T J A1 - Hernandez, J R A1 - Houck, J A1 - Hostin, D A1 - Houston, K A A1 - Howland, T J A1 - Wei, M H A1 - Ibegwam, C A1 - Jalali, M A1 - Kalush, F A1 - Karpen, G H A1 - Ke, Z A1 - Kennison, J A A1 - Ketchum, K A A1 - Kimmel, B E A1 - Kodira, C D A1 - Kraft, C A1 - Kravitz, S A1 - Kulp, D A1 - Lai, Z A1 - Lasko, P A1 - Lei, Y A1 - Levitsky, A A A1 - Li, J A1 - Li, Z A1 - Liang, Y A1 - Lin, X A1 - Liu, X A1 - Mattei, B A1 - McIntosh, T C A1 - McLeod, M P A1 - McPherson, D A1 - Merkulov, G A1 - Milshina, N V A1 - Mobarry, C A1 - Morris, J A1 - Moshrefi, A A1 - Mount, S M A1 - Moy, M A1 - Murphy, B A1 - Murphy, L A1 - Muzny, D M A1 - Nelson, D L A1 - Nelson, D R A1 - Nelson, K A A1 - Nixon, K A1 - Nusskern, D R A1 - Pacleb, J M A1 - Palazzolo, M A1 - Pittman, G S A1 - Pan, S A1 - Pollard, J A1 - Puri, V A1 - Reese, M G A1 - Reinert, K A1 - Remington, K A1 - Saunders, R D A1 - Scheeler, F A1 - Shen, H A1 - Shue, B C A1 - Sidén-Kiamos, I A1 - Simpson, M A1 - Skupski, M P A1 - Smith, T A1 - Spier, E A1 - Spradling, A C A1 - Stapleton, M A1 - Strong, R A1 - Sun, E A1 - Svirskas, R A1 - Tector, C A1 - Turner, R A1 - Venter, E A1 - Wang, A H A1 - Wang, X A1 - Wang, Z Y A1 - Wassarman, D A A1 - Weinstock, G M A1 - Weissenbach, J A1 - Williams, S M A1 - Worley, K C A1 - Wu, D A1 - Yang, S A1 - Yao, Q A A1 - Ye, J A1 - Yeh, R F A1 - Zaveri, J S A1 - Zhan, M A1 - Zhang, G A1 - Zhao, Q A1 - Zheng, L A1 - Zheng, X H A1 - Zhong, F N A1 - Zhong, W A1 - Zhou, X A1 - Zhu, S A1 - Zhu, X A1 - Smith, H O A1 - Gibbs, R A A1 - Myers, E W A1 - Rubin, G M A1 - Venter, J C KW - Animals KW - Biological Transport KW - Chromatin KW - Cloning, Molecular KW - Computational Biology KW - Contig Mapping KW - Cytochrome P-450 Enzyme System KW - DNA Repair KW - DNA Replication KW - Drosophila melanogaster KW - Euchromatin KW - Gene Library KW - Genes, Insect KW - Genome KW - Heterochromatin KW - Insect Proteins KW - Nuclear Proteins KW - Protein Biosynthesis KW - Sequence Analysis, DNA KW - Transcription, Genetic AB -

The fly Drosophila melanogaster is one of the most intensively studied organisms in biology and serves as a model system for the investigation of many developmental and cellular processes common to higher eukaryotes, including humans. We have determined the nucleotide sequence of nearly all of the approximately 120-megabase euchromatic portion of the Drosophila genome using a whole-genome shotgun sequencing strategy supported by extensive clone-based sequence and a high-quality bacterial artificial chromosome physical map. Efforts are under way to close the remaining gaps; however, the sequence is of sufficient accuracy and contiguity to be declared substantially complete and to support an initial analysis of genome structure and preliminary gene annotation and interpretation. The genome encodes approximately 13,600 genes, somewhat fewer than the smaller Caenorhabditis elegans genome, but with comparable functional diversity.

VL - 287 CP - 5461 ER - TY - JOUR T1 - Genomic sequence, splicing, and gene annotation. JF - Am J Hum Genet Y1 - 2000 A1 - Mount, S M KW - Animals KW - Consensus Sequence KW - Exons KW - genes KW - Genome KW - Genomics KW - HUMANS KW - Nucleotides KW - Regulatory Sequences, Nucleic Acid KW - RNA Splice Sites KW - RNA Splicing KW - Untranslated Regions VL - 67 CP - 4 M3 - 10.1086/303098 ER - TY - JOUR T1 - Ligand-Receptor Pairing Via Tree Comparison JF - Journal of Computational BiologyJournal of Computational Biology Y1 - 2000 A1 - Bafna, Vineet A1 - Sridhar Hannenhalli A1 - Rice, Ken A1 - Vawter, Lisa AB - This paper introduces a novel class of tree comparison problems strongly motivated by an important and cost intensive step in drug discovery pipeline viz., mapping cell bound receptors to the ligands they bind to and vice versa. Tree comparison studies motivated by problems such as virus-host tree comparison, gene-species tree comparison and consensus tree problem have been reported. None of these studies are applicable in our context because in all these problems, there is a well-defined mapping of the nodes the trees are built on across the set of trees being compared. A new class of tree comparison problems arises in cases where finding the correspondence among the nodes of the trees being compared is itself the problem. The problem arises while trying to find the interclass correspondence between the members of a pair of coevolving classes, e.g., cell bound receptors and their ligands. Given the evolution of the two classes, the combinatorial problem is to find a mapping among the leaves of the two trees that optimizes a given cost function. In this work we formulate various combinatorial optimization problems motivated by the aforementioned biological problem for the first time. We present hardness results, give an efficient algorithm for a restriction of the problem and demonstrate its applicability. VL - 7 SN - 1066-5277, 1557-8666 ER - TY - JOUR T1 - MDP-1: A novel eukaryotic magnesium-dependent phosphatase JF - BiochemistryBiochemistry Y1 - 2000 A1 - J. Selengut A1 - Levine, R. L. KW - Amino Acid Sequence KW - Animals KW - Catalysis KW - Cations KW - Chromatography, Affinity KW - Cloning, Molecular KW - Cysteine KW - Enzyme Inhibitors KW - Histidine KW - Hydrogen-Ion Concentration KW - Magnesium KW - Mice KW - Molecular Sequence Data KW - Phosphoprotein Phosphatases KW - Protein Phosphatase 1 KW - Rabbits KW - Sequence Analysis, Protein KW - Sequence Homology, Amino Acid KW - Substrate Specificity AB - We report here the purification, cloning, expression, and characterization of a novel phosphatase, MDP-1. In the course of investigating the reported acid phosphatase activity of carbonic anhydrase III preparations, several discrete phosphatases were discerned. One of these, a magnesium-dependent species of 18.6 kDa, was purified to homogeneity and yielded several peptide sequences from which the parent gene was identified by database searching. Although orthologous genes were identified in fungi and plants as well as mammalian species, there was no apparent homology to any known family of phosphatases. The enzyme was expressed in Escherichia coli with a fusion tag and purified by affinity methods. The recombinant enzyme showed magnesium-dependent acid phosphatase activity comparable to the originally isolated rabbit protein. The enzyme catalyzes the rapid hydrolysis of p-nitrophenyl phosphate, ribose-5-phosphate, and phosphotyrosine. The selectivity for phosphotyrosine over phosphoserine or phosphothreonine is considerable, but the enzyme did not show activity toward five phosphotyrosine-containing peptides. None of the various substrates assayed (including various nucleotide, sugar, amino acid and peptide phosphates, phosphoinositides, and phosphodiesters) exhibited K(M) values lower than 1 mM, and many showed negligible rates of hydrolysis. The enzyme is inhibited by vanadate and fluoride but not by azide, cyanide, calcium, lithium, or tartaric acid. Chemical labeling, refolding, dialysis, and mutagenesis experiments suggest that the enzymatic mechanism is not dependent on cysteine, histidine, or nonmagnesium metal ions. In recognition of these observations, the enzyme has been given the name magnesium-dependent phosphatase-1 (MDP-1). VL - 39 N1 - http://www.ncbi.nlm.nih.gov/pubmed/10889041?dopt=Abstract ER - TY - JOUR T1 - Phylogenetic relationships of Acanthocephala based on analysis of 18S ribosomal RNA gene sequences JF - J Mol EvolJ Mol Evol Y1 - 2000 A1 - García-Varela, M. A1 - Pérez-Ponce de León, G. A1 - de la Torre, P. A1 - Michael P. Cummings A1 - Sarma, S. S. A1 - Laclette, J. P. AB - Acanthocephala (thorny-headed worms) is a phylum of endoparasites of vertebrates and arthropods, included among the most phylogenetically basal tripoblastic pseudocoelomates. The phylum is divided into three classes: Archiacanthocephala, Palaeacanthocephala, and Eoacanthocephala. These classes are distinguished by morphological characters such as location of lacunar canals, persistence of ligament sacs in females, number and type of cement glands in males, number and size of proboscis hooks, host taxonomy, and ecology. To understand better the phylogenetic relationships within Acanthocephala, and between Acanthocephala and Rotifera, we sequenced the nearly complete 18S rRNA genes of nine species from the three classes of Acanthocephala and four species of Rotifera from the classes Bdelloidea and Monogononta. Phylogenetic relationships were inferred by maximum-likelihood analyses of these new sequences and others previously determined. The analyses showed that Acanthocephala is the sister group to a clade including Eoacanthocephala and Palaeacanthocephala. Archiacanthocephala exhibited a slower rate of evolution at the nucleotide level, as evidenced by shorter branch lengths for the group. We found statistically significant support for the monophyly of Rotifera, represented in our analysis by species from the clade Eurotatoria, which includes the classes Bdelloidea and Monogononta. Eurotatoria also appears as the sister group to Acanthocephala. VL - 50 ER - TY - JOUR T1 - Phylogenetic relationships of ıt Phytophthora species based on ribosomal ITS I DNA sequence analysis with emphasis on Waterhouse groups V and VI JF - Mycol ResMycol Res Y1 - 2000 A1 - Förster, H. A1 - Michael P. Cummings A1 - Coffey, M. D. AB - Phylogenetic relationships among Phytophthora species were investigated by sequence analysis of the internal transcribed spacer region I of the ribosomal DNA repeat unit. The extensive collection of isolates included taxa from all six morphological groups recognized by Waterhouse (1963) including molecular groups previously identified using isozymes and mtDNA restriction fragment length polymorphisms. Similar to previous studies, the inferred relationships indicated that molecular groups of P. cryptooea/drechsleri-like and P. megasperma-like taxa are polyphyletic. Morphological groups V and VI, which are differentiated by the presence of amphigynous or paragynous antheridia, are not monophyletic: species of the two groups are interspersed in the tree. Species with papillate and semi-papillate sporangia (groups I-IV) clustered together and this cluster was distinct from those of species with non-papillate sporangia. There was no congruence between the mode of antheridial attachment, sporangial caducity, or homo- or heterothallic habit and the molecular grouping of the species. Our study provides evidence that the antheridial position together with homo- or heterothallic habit does not reflect phylogenetic relationships within Phytophthora. Consequently, confirming studies done previously (Cooke & Duncan 1997), this study provides evidence that the morphological characters used in Phytophthora taxonomy are of limited value for deducing phylogenetic relationships, because they exhibit convergent evolution. VL - 104 ER - TY - JOUR T1 - Pre-messenger RNA processing factors in the Drosophila genome. JF - J Cell Biol Y1 - 2000 A1 - Mount, S M A1 - Salz, H K KW - Animals KW - Drosophila melanogaster KW - Genome KW - Genomic Library KW - HUMANS KW - RNA Precursors KW - RNA, Messenger VL - 150 CP - 2 ER - TY - JOUR T1 - Bacterial Start Site Prediction JF - Nucleic Acids ResearchNucl. Acids Res.Nucleic Acids ResearchNucl. Acids Res. Y1 - 1999 A1 - Sridhar Hannenhalli A1 - Hayes, William S. A1 - Hatzigeorgiou, Artemis G. A1 - Fickett, James W. AB - With the growing number of completely sequenced bacterial genes, accurate gene prediction in bacterial genomes remains an important problem. Although the existing tools predict genes in bacterial genomes with high overall accuracy, their ability to pinpoint the translation start site remains unsatisfactory. In this paper, we present a novel approach to bacterial start site prediction that takes into account multiple features of a potential start site, viz., ribosome binding site (RBS) binding energy, distance of the RBS from the start codon, distance from the beginning of the maximal ORF to the start codon, the start codon itself and the coding/non-coding potential around the start site. Mixed integer programing was used to optimize the discriminatory system. The accuracy of this approach is up to 90%, compared to 70%, using the most common tools in fully automated mode (that is, without expert human post-processing of results). The approach is evaluated using Bacillus subtilis, Escherichia coli and Pyrococcus furiosus. These three genomes cover a broad spectrum of bacterial genomes, since B.subtilis is a Gram-positive bacterium, E.coli is a Gram-negative bacterium and P.furiosus is an archaebacterium. A significant problem is generating a set of ‘true’ start sites for algorithm training, in the absence of experimental work. We found that sequence conservation between P.furiosus and the related Pyrococcus horikoshii clearly delimited the gene start in many cases, providing a sufficient training set. VL - 27 SN - 0305-1048, 1362-4962 ER - TY - JOUR T1 - Genes and other samples of DNA sequence data for phylogenetic inference JF - The Biological BulletinThe Biological Bulletin Y1 - 1999 A1 - Michael P. Cummings A1 - Otto, S. P. A1 - Wakeley, J. VL - 196 ER - TY - JOUR T1 - More surprises from Kinetoplastida JF - Proceedings of the National Academy of Sciences of the United States of AmericaProceedings of the National Academy of Sciences of the United States of America Y1 - 1999 A1 - Donelson, J. E. A1 - Gardner, M. J. A1 - Najib M. El‐Sayed VL - 96 ER - TY - CHAP T1 - Multiple mechanisms of immune evasion by African trypanosomes T2 - The Trypanosome Surface Y1 - 1999 A1 - Donelson, J.E. A1 - Hill, K.L. A1 - El-Sayed, N.M.A. JA - The Trypanosome Surface PB - De Boeck & Larcier s.a. CY - Brussels ER - TY - JOUR T1 - Pathogenic mechanisms in ischemic damage: a computational study JF - Computers in biology and medicineComputers in biology and medicine Y1 - 1999 A1 - Ruppin, E. A1 - Ofer, E. A1 - Reggia, James A. A1 - Revett, K. VL - 29 ER - TY - JOUR T1 - Penumbral tissue damage following acute stroke: a computational investigation JF - Progress in brain researchProgress in brain research Y1 - 1999 A1 - Ruppin, E. A1 - Revett, K. A1 - Ofer, E. A1 - Goodall, S. A1 - Reggia, James A. VL - 121 ER - TY - JOUR T1 - Transforming cabbage into turnip: polynomial algorithm for sorting signed permutations by reversals JF - J. ACMJ. ACM Y1 - 1999 A1 - Sridhar Hannenhalli A1 - Pevzner, Pavel A. KW - Computational Biology KW - Genetics AB - Genomes frequently evolve by reversals &rgr;(i,j) that transform a gene order &pgr;1 … &pgr;i&pgr;i+1 … &pgr;j-1&pgr;j … &pgr;n into &pgr;1 … &pgr;i&pgr;j-1 … &pgr;i+1&pgr;j … &pgr;n. Reversal distance between permutations &pgr; and &sgr;is the minimum number of reversals to transform &pgr; into &Agr;. Analysis of genome rearrangements in molecular biology started in the late 1930's, when Dobzhansky and Sturtevant published a milestone paper presenting a rearrangement scenario with 17 inversions between the species of Drosophilia. Analysis of genomes evolving by inversions leads to a combinatorial problem of sorting by reversals studied in detail recently. We study sorting of signed permutations by reversals, a problem that adequately models rearrangements in a small genomes like chloroplast or mitochondrial DNA. The previously suggested approximation algorithms for sorting signed permutations by reversals compute the reversal distance between permutations with an astonishing accuracy for both simulated and biological data. We prove a duality theorem explaining this intriguing performance and show that there exists a “hidden” parameter that allows one to compute the reversal distance between signed permutations in polynomial time. VL - 46 SN - 0004-5411 ER - TY - CHAP T1 - De-amortization of Algorithms T2 - Computing and CombinatoricsComputing and Combinatorics Y1 - 1998 A1 - Rao Kosaraju, S. A1 - M. Pop ED - Hsu, Wen-Lian ED - Kao, Ming-Yang AB - De-amortization aims to convert algorithms with excellent overall speed, f ( n ) for performing n operations, into algorithms that take no more than O ( f ( n )/ n ) steps for each operation. The paper reviews several existing techniques for de-amortization of algorithms. JA - Computing and CombinatoricsComputing and Combinatorics T3 - Lecture Notes in Computer Science PB - Springer Berlin / Heidelberg VL - 1449 SN - 978-3-540-64824-6 ER - TY - CHAP T1 - Drawing of Two-Dimensional Irregular Meshes T2 - Graph DrawingGraph Drawing Y1 - 1998 A1 - Aggarwal, Alok A1 - Rao Kosaraju, S. A1 - M. Pop ED - Whitesides, Sue AB - We present a method for transforming two-dimensional irregular meshes into square meshes with only a constant blow up in area. We also explore context invariant transformations of irregular meshes into square meshes and provide a lower bound for the transformation of down-staircases. JA - Graph DrawingGraph Drawing T3 - Lecture Notes in Computer Science PB - Springer Berlin / Heidelberg VL - 1547 SN - 978-3-540-65473-5 ER - TY - JOUR T1 - The effect of calprotectin on the nucleation and growth of struvite crystals as assayed by light microscopy in real-time JF - The Journal of urologyThe Journal of urology Y1 - 1998 A1 - Asakura, H. A1 - J. Selengut A1 - Orme-Johnson, W. H. A1 - Dretler, S. P. KW - Crystallization KW - Dose-Response Relationship, Drug KW - Leukocyte L1 Antigen Complex KW - Magnesium Compounds KW - Neural Cell Adhesion Molecules KW - Phosphates KW - Time factors AB - PURPOSE: To use light microscopy to observe the urease-induced growth of struvite crystals in real-time, and to compare the effects of various proteins on that growth. MATERIALS AND METHODS: Artificial urine, with and without citrate, and a minimal urine solution containing only urea and the components of struvite and apatite were incubated with urease and test proteins in the depressions of culture slides. The number and size of rectangular and X-shaped struvite crystals were recorded using a low-power phase contrast microscope. RESULTS: The formation of crystalline struvite appears to occur after the formation of an amorphous calcium- and magnesium-containing phase. The extent of this amorphous phase is dependent on the presence of calcium and citrate, both of which strongly promote its formation over the crystalline phase. alpha-globulin, gamma-globulin and chymotrypsin inhibitor all result in the same amount of crystalline struvite as bovine serum albumin which is used as a control. Calprotectin, on the other hand, causes consistent and significant reductions in the number and size of struvite crystals under a wide range of conditions. No changes in the morphology of the struvite crystals were observed. CONCLUSIONS: Calprotectin, the dominant protein of infection stone matrix, has distinctive properties which affect the formation and growth of struvite crystals. The presence of citrate in synthetic urine dramatically reduces the number of struvite crystals observed. The present method for observing the effects of putative infection stone inhibitors appears to have merit. VL - 159 N1 - http://www.ncbi.nlm.nih.gov/pubmed/9507889?dopt=Abstract ER - TY - JOUR T1 - Genetic nomenclature for Trypanosoma and Leishmania. JF - Mol Biochem Parasitol Y1 - 1998 A1 - Clayton, C A1 - Adams, M A1 - Almeida, R A1 - Baltz, T A1 - Barrett, M A1 - Bastien, P A1 - Belli, S A1 - Beverley, S A1 - Biteau, N A1 - Blackwell, J A1 - Blaineau, C A1 - Boshart, M A1 - Bringaud, F A1 - Cross, G A1 - Cruz, A A1 - Degrave, W A1 - Donelson, J A1 - El-Sayed, N A1 - Fu, G A1 - Ersfeld, K A1 - Gibson, W A1 - Gull, K A1 - Ivens, A A1 - Kelly, J A1 - Vanhamme, L KW - Animals KW - Leishmania KW - Terminology as Topic KW - Trypanosoma VL - 97 CP - 1-2 ER - TY - JOUR T1 - Multiple mechanisms of immune evasion by African trypanosomes JF - Molecular and Biochemical ParasitologyMolecular and Biochemical Parasitology Y1 - 1998 A1 - Donelson, John E. A1 - Hill, Kent L. A1 - Najib M. El‐Sayed KW - Leishmania KW - Recombinant cloning KW - T cell KW - Trypanosomes KW - VSG genes AB - During infection of a mammalian host, African trypanosomes are in constant contact with the host's immune system. These protozoan parasites are infamous for their ability to evade the immune responses by periodically switching their major variant surface glycoprotein (VSG), a phenomenon called antigenic variation. Antigenic variation, however, is likely to be only one of several mechanisms enabling these organisms to thrive in the face of the immune defenses. The ability to grow in high levels of interferon-gamma (IFN-[gamma]) and to avoid complement-mediated destruction may also facilitate the parasite's survival. In this review we summarize (i) the activation of trypanosome genes for three different VSGs during antigenic variation, (ii) the secretion of a trypanosome protein that induces host CD8+ T cells to produce IFN-[gamma], and (iii) the evidence for trypansome protein similar to a surface protease of Leishmania that plays a role in resistance to complement-mediated lysis. VL - 91 SN - 0166-6851 ER - TY - JOUR T1 - Nucleotide sequence diversity at the alcohol dehydrogenase 1 locus in wild barley (ıt Hordeum vulgare ssp. ıt spontaneum): an evaluation of the background selection hypothesis JF - Proc Natl Acad Sci USAProc Natl Acad Sci USA Y1 - 1998 A1 - Michael P. Cummings A1 - Clegg, M. T. AB - The background selection hypothesis predicts a reduction in nucleotide site diversity and an excess of rare variants, owing to linkage associations with deleterious alleles. This effect is expected to be amplified in species that are predominantly self-fertilizing. To examine the predictions of the background selection hypothesis in self-fertilizing species, we sequenced 1,362 bp of adh1, a gene for alcohol dehydrogenase (Adh; alcohol:NAD+ oxidoreductase, EC 1.1.1.1), in a sample of 45 accessions of wild barley, Hordeum vulgare ssp. spontaneum, drawn from throughout the species range. The region sequenced included 786 bp of exon sequence (part of exon 4, all of exons 5-9, and part of exon 10) and 576 bp of intron sequence (all of introns 4-9). There were 19 sites polymorphic for nucleotide substitutions, 8 in introns, and 11 in exons. Of the 11 nucleotide substitutions in codons, 4 were synonymous and 7 were nonsynonymous, occurring uniquely in the sample. There was no evidence of recombination in the region studied, and the estimated effective population size (Ne) based on synonymous sites was approximately 1.8-4.2 x 10(5). Several tests reveal that the pattern of nonsynonymous substitutions departs significantly from neutral expectations. However, the data do not appear to be consistent with recovery from a population bottleneck, recent population expansion, selective sweep, or strong positive selection. Though several features of the data are consistent with background selection, the distributions of polymorphic synonymous and intron sites are not perturbed toward a significant excess of rare alleles as would be predicted by background selection. VL - 95 ER - TY - JOUR T1 - Phylogenetic relationships of platyhelminthes based on 18S ribosomal gene sequences JF - Mol Phylogenet EvolMol Phylogenet Evol Y1 - 1998 A1 - Campos, A. A1 - Michael P. Cummings A1 - Reyes, J. L. A1 - Laclette, J. P. AB - Nucleotide sequences of 18S ribosomal RNA from 71 species of Platyhelminthes, the flatworms, were analyzed using maximum likelihood, and the resulting phylogenetic trees were compared with previous phylogenetic hypotheses. Analyses including 15 outgroup species belonging to eight other phyla show that Platyhelminthes are monophyletic with the exception of a sequence putatively from Acoela sp., Lecithoepitheliata, Polycladida, Tricladida, Trematoda (Aspidobothrii + Digenea), Monogenea, and Cestoda (Gyrocotylidea + Amphilinidea + Eucestoda) are monophyletic groups. Catenulids form the sister group to the rest of platyhelminths, whereas a complex clade formed by Acoela, Tricladida, "Dalyellioida", and perhaps "Typhloplanoida" is sister to Neodermata. "Typhloplanoida" does not appear to be monophyletic; Fecampiida does not appear to belong within "Dalyellioida," nor Kalyptorhynchia within "Typhloplanoida." Trematoda is the sister group to the rest of Neodermata, and Monogenea is sister group to Cestoda. Within Trematoda, Aspidobothrii is the sister group of Digenea and Heronimidae is the most basal family in Digenea. Our trees support the hypothesis that parasitism evolved at least twice in Platyhelminthes, once in the ancestor to Neodermata and again in the ancestor of Fecampiida, independently to the ancestor of putatively parasitic "Dalyellioida." VL - 10 ER - TY - JOUR T1 - Pigment composition of putatively achlorophyllous angiosperms JF - Plant Syst EvolPlant Syst Evol Y1 - 1998 A1 - Michael P. Cummings A1 - Welschmeyer, N. A. KW - Angiospermae KW - carotenoid KW - chlorophyll KW - high-performance liquid chromatography KW - Lennoaceae KW - Monotropaceae KW - Orchidaceae KW - Orobanchaceae KW - pigment AB - Chlorophyll and carotenoid pigment composition was determined for ten species of putatively achlorophyllous angiosperms using high-performance liquid chromatography. Four families were represented: Lennoaceae (Pholisma arenarium); Monotropaceae (Allotropa virgata, Monotropa uniflora, Pterospora andromedea, Sarcodes sanguinea); Orobanchaceae (Epifagus virginiana, Orobanche cooperi, O. uniflora); Orchidaceae (Cephalanthera austinae, Corallorhiza maculata). Chlorophyll a was detected in all tars, but chlorophyll b was only detected in Corallorhiza maculata. The relative amount of chlorophyll and chlorophyll-related pigments in these plants is greatly reduced compared to fully autotrophic angiosperms. VL - 210 ER - TY - JOUR T1 - Spreading depression in focal ischemia: A computational study JF - Journal of Cerebral Blood Flow & MetabolismJournal of Cerebral Blood Flow & Metabolism Y1 - 1998 A1 - Revett, K. A1 - Ruppin, E. A1 - Goodall, S. A1 - Reggia, James A. VL - 18 ER - TY - JOUR T1 - Trends in the early careers of life scientists - Preface and executive summary JF - Mol Biol CellMol Biol Cell Y1 - 1998 A1 - Tilghman, S. A1 - Astin, H. S. A1 - Brinkley, W. A1 - Chilton, M. D. A1 - Michael P. Cummings A1 - Ehrenberg, R. G. A1 - Fox, M. F. A1 - Glenn, K. A1 - Green, P. J. A1 - Hans, S. A1 - Kelman, A. A1 - LaPidus, J. A1 - Levin, B. A1 - McIntosh, J. R. A1 - Riecken, H. A1 - Stephen, P. E. VL - 9 ER - TY - JOUR T1 - African trypanosomes have differentially expressed genes encoding homologues of the Leishmania GP63 surface protease JF - Journal of Biological ChemistryJournal of Biological Chemistry Y1 - 1997 A1 - Najib M. El‐Sayed A1 - Donelson, J. E. VL - 272 ER - TY - JOUR T1 - A computational model of acute focal cortical lesions JF - StrokeStroke Y1 - 1997 A1 - Goodall, S. A1 - Reggia, James A. A1 - Chen, Y. A1 - Ruppin, E. A1 - Whitney, C. VL - 28 ER - TY - JOUR T1 - Computer models: A new approach to the investigation of disease JF - MD ComputingMD Computing Y1 - 1997 A1 - Reggia, James A. A1 - Ruppin, E. A1 - Berndt, R. S. VL - 14 ER - TY - JOUR T1 - The evolution of plant nuclear genes JF - Proc Natl Acad Sci USAProc Natl Acad Sci USA Y1 - 1997 A1 - Clegg, M. T. A1 - Michael P. Cummings A1 - Durbin, M. L. AB - We analyze the evolutionary dynamics of three of the best-studied plant nuclear multigene families. The data analyzed derive from the genes that encode the small subunit of ribulose-1,5-bisphosphate carboxylase (rbcS), the gene family that encodes the enzyme chalcone synthase (Chs), and the gene family that encodes alcohol dehydrogenases (Adh). In addition, we consider the limited evolutionary data available on plant transposable elements. New Chs and rbcS genes appear to be recruited at about 10 times the rate estimated for Adh genes, and this is correlated with a much smaller average gene family size for Adh genes. In addition, duplication and divergence in function appears to be relatively common for Chs genes in flowering plant evolution. Analyses of synonymous nucleotide substitution rates for Adh genes in monocots reject a linear relationship with clock time. Replacement substitution rates vary with time in a complex fashion, which suggests that adaptive evolution has played an important role in driving divergence following gene duplication events. Molecular population genetic studies of Adh and Chs genes reveal high levels of molecular diversity within species. These studies also reveal that inter- and intralocus recombination are important forces in the generation allelic novelties. Moreover, illegitimate recombination events appear to be an important factor in transposable element loss in plants. When we consider the recruitment and loss of new gene copies, the generation of allelic diversity within plant species, and ectopic exchange among transposable elements, we conclude that recombination is a pervasive force at all levels of plant evolution. VL - 94 ER - TY - JOUR T1 - Genetic depletion reveals an essential role for an SR protein splicing factor in vertebrate cells. JF - Bioessays Y1 - 1997 A1 - Mount, S M KW - Amino Acid Sequence KW - Animals KW - Molecular Sequence Data KW - Nuclear Proteins KW - RNA Splicing KW - RNA-Binding Proteins KW - Serine-Arginine Splicing Factors KW - Vertebrates AB -

SR proteins are essential for the splicing of messenger RNA precursors in vitro, where they also alter splice site selection in a concentration-dependent manner. Although experiments involving overexpression or dominant mutations have confirmed that these proteins can influence RNA processing decisions in vivo, similar results with loss-of-function mutations have been lacking. Now, a system for genetic depletion of the chicken B cell line DT40 has revealed that the SR protein ASF/SF2 (alternative splicing factor/splicing factor 2) is essential for viability in these cells(1). This study opens the way for a complete functional dissection of this protein, and other SR proteins, in vivo.

VL - 19 CP - 3 M3 - 10.1002/bies.950190302 ER - TY - JOUR T1 - Hardness of flip-cut problems from optical mapping JF - Journal of Computational BiologyJournal of Computational Biology Y1 - 1997 A1 - DanČÍK, V. A1 - Sridhar Hannenhalli A1 - Muthukrishnan, S. VL - 4 ER - TY - JOUR T1 - Local rules for protein folding on a triangular lattice and generalized hydrophobicity in the HP model JF - Journal of Computational BiologyJournal of Computational Biology Y1 - 1997 A1 - Agarwala, R. A1 - Batzoglou, S. A1 - DanČÍK, V. A1 - Decatur, S. E. A1 - Sridhar Hannenhalli A1 - Farach, M. A1 - Muthukrishnan, S. A1 - Skiena, S. VL - 4 ER - TY - JOUR T1 - Satellite DNA repeat sequence variation is low in three species of burying beetles in the genus ıt Nicrophorus (Coleoptera: Silphidae) JF - Mol Biol EvolMol Biol Evol Y1 - 1997 A1 - King, L. M. A1 - Michael P. Cummings AB - Three satellite DNA families were identified in three species of burying beetles, Nicrophorus orbicollis, N. marginatus, and N. americanus. Southern hybridization and nucleotide sequence analysis of individual randomly cloned repeats shows that these satellite DNA families are highly abundant in the genome, are composed of unique repeats, and are species-specific. The repeats do not have identifiable core elements or substructures that are similar in all three families, and most interspecific sequence similarity is confined to homopolymeric runs of A and T. Satellite DNA from N. marginatus and N. americanus show single-base-pair indels among repeats, but single-nucleotide substitutions characterize most of the repeat variability. Although the repeat units are of similar lengths (342, 350, and 354 bp) and A + T composition (65%, 71%, and 71%, respectively), the average nucleotide divergence among sequenced repeats is very low (0.18%, 1.22%, and 0.71%, respectively). Transition/transversion ratios from the consensus sequence are 0.20, 0.69, and 0.70, respectively. VL - 14 ER - TY - CHAP T1 - Sequencing and mapping the African trypanosome genome T2 - Trypanosomiasis and Leishmaniasis: Biology and Control Y1 - 1997 A1 - El-Sayed, N.M.A A1 - Donelson, J.E. JA - Trypanosomiasis and Leishmaniasis: Biology and Control PB - CAB International and the British Society for Parasitology pubs ER - TY - JOUR T1 - A survey of the Trypanosoma brucei rhodesiense genome using shotgun sequencing JF - Molecular and Biochemical ParasitologyMolecular and Biochemical Parasitology Y1 - 1997 A1 - Najib M. El‐Sayed A1 - Donelson, John E. KW - Expressed sequence tag KW - Genome survey sequence KW - Trypanosoma brucei rhodesiense AB - A comparison of the efficiency of sequencing random genomic DNA fragments versus random cDNAs for the discovery of new genes in African trypanosomes was undertaken. Trypanosome DNA was sheared to a 1.5-2.5 kb size distribution, cloned into a plasmid and the sequences at both ends of 183 cloned fragments determined. Sequences of both kinetoplast and nuclear DNA were identified. New coding regions were discovered for a variety of proteins, including cell division proteins, an RNA-binding protein and a homologue of the Leishmania surface protease GP63. In some cases, each end of a fragment was found to contain a different gene, demonstrating the proximity of those genes and suggesting that the density of genes in the African trypanosome genome is quite high. Repetitive sequence elements found included telomeric hexamer repeats, 76 bp repeats associated with VSG gene expression sites, 177 bp satellite repeats in minichromosomes and the Ingi transposon-like elements. In contrast to cDNA sequencing, no ribosomal protein genes were detected. For the sake of comparison, the sequences of 190 expressed sequence tags (ESTs) were also determined, and a similar number of new trypanosomal homologues were found including homologues of another putative surface protein and a human leucine-rich repeat-containing protein. We conclude from this analysis and our previous work that sequencing random DNA fragments in African trypanosomes is as efficient for gene discovery as is sequencing random cDNA clones. VL - 84 SN - 0166-6851 ER - TY - JOUR T1 - Testing simple polygons JF - Computational GeometryComputational Geometry Y1 - 1997 A1 - Arkin, Esther M. A1 - Belleville, Patrice A1 - Mitchell, Joseph S. B. A1 - Mount, Dave A1 - Romanik, Kathleen A1 - Salzberg, Steven A1 - Souvaine, Diane KW - probing KW - Testing KW - Verifying AB - We consider the problem of verifying a simple polygon in the plane using “test points”. A test point is a geometric probe that takes as input a point in Euclidean space, and returns “+” if the point is inside the object being probed or “−” if it is outside. A verification procedure takes as input a description of a target object, including its location and orientation, and it produces a set of test points that are used to verify whether a test object matches the description. We give a procedure for verifying an n-sided, non-degenerate, simple target polygon using 5n test points. This testing strategy works even if the test polygon has n + 1 vertices, and we show a lower bound of 3n + 1 test points for this case. We also give algorithms using O(n) test points for simple polygons that may be degenerate and for test polygons that may have up to n + 2 vertices. All of these algorithms work for polygons with holes. We also discuss extensions of our results to higher dimensions. VL - 8 SN - 0925-7721 ER - TY - JOUR T1 - AT-AC introns: an ATtACk on dogma. JF - Science Y1 - 1996 A1 - Mount, S M KW - Animals KW - Base Composition KW - Base Sequence KW - Consensus Sequence KW - HUMANS KW - Introns KW - Molecular Sequence Data KW - Mutation KW - RNA Precursors KW - RNA Splicing KW - RNA, Small Nuclear KW - Spliceosomes VL - 271 CP - 5256 ER - TY - JOUR T1 - Computational studies of synaptic alterations in Alzheimer’s disease JF - Neural modeling of brain and cognitive disordersNeural modeling of brain and cognitive disorders Y1 - 1996 A1 - Ruppin, E. A1 - Horn, D. A1 - Levy, N. A1 - Reggia, James A. ER - TY - JOUR T1 - Differential expression of the expression site-associated gene I family in African trypanosomes JF - Journal of Biological ChemistryJournal of Biological Chemistry Y1 - 1996 A1 - Morgan, R. W. A1 - Najib M. El‐Sayed A1 - Kepa, J. K. A1 - Pedram, M. A1 - Donelson, J. E. VL - 271 ER - TY - JOUR T1 - DNA sequence variation in the ribosomal internal transcribed spacer region of freshwater ıt Cladophora species (Chlorophyta) JF - J PhycolJ Phycol Y1 - 1996 A1 - Marks, J. C. A1 - Michael P. Cummings KW - algae KW - Chlorophyta KW - Cladophora KW - diversity KW - freshwater KW - genetic KW - internal KW - spacer KW - transcribed AB - Freshwater species of Cladophora (Chlorophyta) are globally distributed and occupy an unusually wide range of ecological habitats. Delineating species is difficult because most easily observed morphological traits are highly variable and because sexual reproduction has not been clearly documented. Synthesizing ecological data on freshwater Cladophora species is problematic because it is unclear whether freshwater Cladophora species comprise many genetically distinct species or a few ecologically and morphologically variable and / or plastic species. We determined nucleotide sequences of the internal transcribed spacer (ITS) region of the nuclear ribosomal cistron of freshwater Cladophora species from a wide range of habitats and geographic locations. We compared these sequences to those derived from culture collections of C. fracta and C. glomerata, the two most commonly reported freshwater Cladophora species. Cladophora fracta and C. glomerata had very similar ITS sequences (95.3%). All other sequences were identical to those from the C. fracta or C. glomerata culture collections with the exception of one California sample that was similar to both C. fracta (95.6%) and C. glomerata (92.4%). ITS genotypes did not correlate with morphology or geography. This analysis shows that common freshwater Cladophora species comprise very few (possibly one) ecologically and morphologically variable species. VL - 32 ER - TY - JOUR T1 - Evolutionary biology of parasitic platyhelminths: The role of molecular phylogenetics JF - Parasitol TodayParasitol Today Y1 - 1996 A1 - Blair, D. A1 - Campos, A. A1 - Michael P. Cummings A1 - Laclette, J. P. AB - As our appreciation of the diversity within the flatworms has grown, so too has our curiosity about the ways in which these varied creatures are related to one another. In particular, the parasitic groups (trematodes, cestodes and monogeneans have been the focus of enquiry. Until recently, morphology, anatomy and life histories have provided the raw data for building hypotheses on relationships. Now, ultrastructural evidence, and most recently, molecular data from nucleic acid sequences, have been brought to bear on the topic. Here, David Blair, Andrés Campos, Michael Cummings and Juan Pedro Laclette discuss the ways in which molecular data, in particular, are helping us recognize the various lineages of flatworms. VL - 12 ER - TY - CHAP T1 - Fast sorting by reversal T2 - Combinatorial Pattern MatchingCombinatorial Pattern Matching Y1 - 1996 A1 - Berman, Piotr A1 - Sridhar Hannenhalli ED - Hirschberg, Dan ED - Myers, Gene AB - Analysis of genomes evolving by inversions leads to a combinatorial problem of sorting by reversals studied in detail recently. Following a series of work recently, Hannenhalli and Pevzner developed the first polynomial algorithm for the problem of sorting signed permutations by reversals and proposed an O(n 4 ) implementation of the algorithm. In this paper we exploit a few combinatorial properties of the cycle graph of a permutation and propose an O(n 2 (n)) implementation of the algorithm where is the inverse Ackerman function. Besides making this algorithm practical, our technique improves implementations of the other rearrangement distance problems. JA - Combinatorial Pattern MatchingCombinatorial Pattern Matching T3 - Lecture Notes in Computer Science PB - Springer Berlin / Heidelberg VL - 1075 SN - 978-3-540-61258-2 ER - TY - CHAP T1 - Inferring phylogenies from DNA sequence data: The effects of sampling T2 - New Uses for New PhylogeniesNew Uses for New Phylogenies Y1 - 1996 A1 - Otto, S. P. A1 - Michael P. Cummings A1 - Wakeley, J. ED - Harvey, P. H. ED - Leigh Brown, A. J. ED - Maynard Smith, J. ED - Nee, S. JA - New Uses for New PhylogeniesNew Uses for New Phylogenies PB - Oxford University Press ER - TY - JOUR T1 - A neural model of positive schizophrenic symptoms JF - Schizophrenia BulletinSchizophrenia Bulletin Y1 - 1996 A1 - Ruppin, E. A1 - Reggia, James A. A1 - Horn, D. VL - 22 ER - TY - JOUR T1 - Pathogenesis of schizophrenic delusions and hallucinations: a neural model JF - Schizophrenia bulletinSchizophrenia Bulletin Y1 - 1996 A1 - Ruppin, E. A1 - Reggia, James A. A1 - Horn, D. VL - 22 ER - TY - JOUR T1 - Polynomial-time algorithm for computing translocation distance between genomes JF - Discrete Applied MathematicsDiscrete Applied Mathematics Y1 - 1996 A1 - Sridhar Hannenhalli AB - With the advent of large-scale DNA physical mapping and sequencing, studies of genome rearrangements are becoming increasingly important in evolutionary molecular biology. From a computational perspective, the study of evolution based on rearrangements leads to a rearrangement distance problem, i.e., computing the minimum number of rearrangement events required to transform one genome into another. Different types of rearrangement events give rise to a spectrum of interesting combinatorial problems. The complexity of most of these problems is unknown. Multichromosomal genomes frequently evolve by a rearrangement event called translocation which exchanges genetic material between different chromosomes. In this paper we study the translocation distance problem, modeling the evolution of genomes evolving by translocations. The translocation distance problem was recently studied for the first time by Kececioglu and Ravi, who gave a 2-approximation algorithm for computing translocation distance. In this paper we prove a duality theorem leading to a polynomial time algorithm for computing translocation distance for the case when the orientations of the genes are known. This leads to an algorithm generating a most parsimonious (shortest) scenario, transforming one genome into another by translocations. VL - 71 SN - 0166-218X ER - TY - JOUR T1 - Positional sequencing by hybridization JF - Computer applications in the biosciences : CABIOSComputer applications in the biosciences : CABIOS Y1 - 1996 A1 - Sridhar Hannenhalli A1 - Feldman, William A1 - Lewis, Herbert F. A1 - Skiena, Steven S. A1 - Pevzner, Pavel A. AB - Sequencing by hybridization (SBH) is a promising alternative to the classical DNA sequencing approaches. However, the resolving power of SBH is rather low: with 64kb sequencing chips, unknown DNA fragments only as long as 200 bp can be reconstructed in a single SBH experiment. To improve the resolving power of SBH, positional SBH (PSBH) has recently been suggested; this allows (with additional experimental work) approximate positions of every l-tuple in a target DNA fragment to be measured. We study the positional Eulerian path problem motivated by PSBH. The input to the positional eulerian path problem is an Eulerian graph G( V, E) in which every edge has an associated range of integers and the problem is to find an Eulerian path el, …, e|E| in G such that the range of ei, contains i. We show that the positional Eulerian path problem is NP-complete even when the maximum out-degree (in-degree) of any vertex in the graph is 2. On a positive note we present polynomial algorithms to solve a special case of PSBH (bounded PSBH), where the range of the allowed positions for any edge is bounded by a constant (it corresponds to accurate experimental measurements of positions in PSBH). Moreover, if the positions of every l-tuple in an unknown DNA fragment of length n are measured with O(log n) error, then our algorithm runs in polynomial time. We also present an estimate of the resolving power of PSBH for a more realistic case when positions are measured with Θ(n) error. VL - 12 ER - TY - JOUR T1 - Ribosomal RNA: small nucleolar RNAs make their mark. JF - Curr Biol Y1 - 1996 A1 - Peculis, B A A1 - Mount, S M KW - Animals KW - Methylation KW - Ribonucleoproteins, Small Nuclear KW - RNA, Ribosomal AB -

Small nucleolar RNAs direct the location of certain methylations in ribosomal RNA by direct base pairing; although evolutionarily conserved, the physiological significance of these modifications remains unclear.

VL - 6 CP - 11 ER - TY - Generic T1 - To cut… or not to cut (applications of comparative physical maps in molecular evolution) T2 - Proceedings of the seventh annual ACM-SIAM symposium on Discrete algorithms Y1 - 1996 A1 - Sridhar Hannenhalli A1 - Pevzner, Pavel JA - Proceedings of the seventh annual ACM-SIAM symposium on Discrete algorithms T3 - SODA '96 PB - Society for Industrial and Applied Mathematics CY - Philadelphia, PA, USA SN - 0-89871-366-8 ER - TY - JOUR T1 - cDNA expressed sequence tags of Trypanosoma brucei rhodesiense provide new insights into the biology of the parasite JF - Molecular and Biochemical ParasitologyMolecular and Biochemical Parasitology Y1 - 1995 A1 - Najib M. El‐Sayed A1 - Alarcon, Clara M. A1 - Beck, John C. A1 - Sheffield, Val C. A1 - Donelson, John E. KW - cDNA KW - Expressed sequence tag KW - Trypanosoma brucei rhodesiense AB - A total of 518 expressed sequence tags (ESTs) have been generated from clones randomly selected from a cDNA library and a spliced leader sub-library of a Trypanosoma brucei rhodesiense bloodstream clone. 205 (39%) of the clones were identified based on matches to 113 unique genes in the public databases. Of these, 71 cDNAs display significant similarities to genes in unrelated organisms encoding metabolic enzymes, signal transduction proteins, transcription factors, ribosomal proteins, histones, a proliferation-associated protein and thimet oligopeptidase, among others. 313 of the cDNAs are not related to any other sequences in the databases. These cDNA ESTs provide new avenues of research for exploring both the novel trypanosome-specific genes and the genome organization of this parasite, as well as a resource for identifying trypanosome homologs to genes expressed in other organisms. VL - 73 SN - 0166-6851 ER - TY - JOUR T1 - Crystallization and preliminary X-ray investigation of the recombinant Trypanosoma brucei rhodesiense calmodulin JF - Proteins: Structure, Function, and BioinformaticsProteins: Structure, Function, and Bioinformatics Y1 - 1995 A1 - Najib M. El‐Sayed A1 - Patton, C. L. A1 - Harkins, P. C. A1 - Fox, R. O. A1 - Anderson, K. VL - 21 ER - TY - JOUR T1 - Genetic enhancement of RNA-processing defects by a dominant mutation in B52, the Drosophila gene for an SR protein splicing factor. JF - Mol Cell Biol Y1 - 1995 A1 - Peng, X A1 - Mount, S M KW - Alleles KW - Amino Acid Sequence KW - Animals KW - Base Sequence KW - DNA Primers KW - Drosophila melanogaster KW - Drosophila Proteins KW - Frameshift Mutation KW - Genes, Dominant KW - Genes, Insect KW - Molecular Sequence Data KW - Nuclear Proteins KW - Phosphoproteins KW - Point Mutation KW - Protein Structure, Tertiary KW - Proteins KW - RNA Splicing KW - RNA-Binding Proteins KW - Sequence Deletion KW - Sex Determination Analysis AB -

SR proteins are essential for pre-mRNA splicing in vitro, act early in the splicing pathway, and can influence alternative splice site choice. Here we describe the isolation of both dominant and loss-of-function alleles of B52, the gene for a Drosophila SR protein. The allele B52ED was identified as a dominant second-site enhancer of white-apricot (wa), a retrotransposon insertion in the second intron of the eye pigmentation gene white with a complex RNA-processing defect. B52ED also exaggerates the mutant phenotype of a distinct white allele carrying a 5' splice site mutation (wDR18), and alters the pattern of sex-specific splicing at doublesex under sensitized conditions, so that the male-specific splice is favored. In addition to being a dominant enhancer of these RNA-processing defects, B52ED is a recessive lethal allele that fails to complement other lethal alleles of B52. Comparison of B52ED with the B52+ allele from which it was derived revealed a single change in a conserved amino acid in the beta 4 strand of the first RNA-binding domain of B52, which suggests that altered RNA binding is responsible for the dominant phenotype. Reversion of the B52ED dominant allele with X rays led to the isolation of a B52 null allele. Together, these results indicate a critical role for the SR protein B52 in pre-mRNA splicing in vivo.

VL - 15 CP - 11 ER - TY - JOUR T1 - Genome Sequence Comparison and Scenarios for Gene Rearrangements: A Test Case JF - GenomicsGenomics Y1 - 1995 A1 - Sridhar Hannenhalli A1 - Chappey, Colombe A1 - Koonin, Eugene V. A1 - Pevzner, Pavel A. AB - As large portions of related genomes are being sequenced, methods for comparing complete or nearly complete genomes, as opposed to comparing individual genes, are becoming progressively more important. A major, widespread phenomenon in genome evolution is the rearrangement of genes and gene blocks. There is, however, no consistent method for genome sequence comparison combined with the reconstruction of the evolutionary history of highly rearranged genomes. We developed a schema for genome sequence comparison that includes three successive steps: (i) comparison of all proteins encoded in different genomes and generation of genomic similarity plots; (ii) construction of an alphabet of conserved genes and gene blocks; and (iii) generation of most parsimonious genome rearrangement scenarios. The approach is illustrated by a comparison of the herpesvirus genomes that constitute the largest set of relatively long, complete genome sequences available to date. Herpesviruses have from 70 to about 200 genes; comparison of the amino acid sequences encoded in these genes results in an alphabet of about 30 conserved genes comprising 7 conserved blocks that are rearranged in the genomes of different herpesviruses. Algorithms to analyze rearrangements of multiple genomes were developed and applied to the derivation of most parsimonious scenarios of herpesvirus evolution under different evolutionary models. The developed approaches to genome comparison will be applicable to the comparative analysis of bacterial and eukaryotic genomes as soon as their sequences become available. VL - 30 SN - 0888-7543 ER - TY - JOUR T1 - Genome sequence comparison and scenarios for gene rearrangements: A test case JF - GenomicsGenomics Y1 - 1995 A1 - Sridhar Hannenhalli A1 - Chappey, C. A1 - Koonin, E. V. A1 - Pevzner, P. A. A1 - others, PB - San Diego: Academic Press, c1987- VL - 30 ER - TY - JOUR T1 - Localization of sequences required for size-specific splicing of a small Drosophila intron in vitro. JF - J Mol Biol Y1 - 1995 A1 - Guo, M A1 - Mount, S M KW - Animals KW - Base Sequence KW - Cell Line KW - DNA KW - Drosophila KW - Genes, Insect KW - HeLa Cells KW - HUMANS KW - Introns KW - Molecular Sequence Data KW - Myosin Heavy Chains KW - RNA Splicing KW - Species Specificity AB -

Many introns in Drosophila and other invertebrates are less than 80 nucleotides in length, too small to be recognized by the vertebrate splicing machinery. Comparison of nuclear splicing extracts from human HeLa and Drosophila Kc cells has revealed species-specificity, consistent with the observed size differences. Here we present additional results with the 68 nucleotide fifth intron of the Drosophila myosin heavy chain gene. As observed with the 74 nucleotide second intron of the Drosophila white gene, the wild-type myosin intron is accurately spliced in a homologous extract, and increasing the size by 16 nucleotides both eliminates splicing in the Drosophila extract and allows accurate splicing in the human extract. In contrast to previous results, however, an upstream cryptic 5' splice site is activated when the wild-type myosin intron is tested in a human HeLa cell nuclear extract, resulting in the removal of a 98 nucleotide intron. The size dependence of splicing in Drosophila extracts is also intron-specific; we noted that a naturally larger (150 nucleotide) intron from the ftz gene is efficiently spliced in Kc cell extracts that do not splice enlarged introns (of 84, 90, 150 or 350 nucleotides) derived from the 74 nucleotide white intron. Here, we have exploited that observation, using a series of hybrid introns to show that a region of 46 nucleotides at the 3' end of the white intron is sufficient to confer the species-specific size effect. At least two sequence elements within this region, yet distinct from previously described branchpoint and pyrimidine tract signals, are required for efficient splicing of small hybrid introns in vitro.

VL - 253 CP - 3 M3 - 10.1006/jmbi.1995.0564 ER - TY - JOUR T1 - A neural model of delusions and hallucinations in schizophrenia JF - Advances in Neural Information Processing SystemsAdvances in Neural Information Processing Systems Y1 - 1995 A1 - Ruppin, E. A1 - Reggia, James A. A1 - Horn, D. ER - TY - JOUR T1 - A neural model of memory impairment in diffuse cerebral atrophy JF - The British Journal of PsychiatryThe British Journal of Psychiatry Y1 - 1995 A1 - Ruppin, E. A1 - Reggia, James A. VL - 166 ER - TY - JOUR T1 - Patterns of functional damage in neural network models of associative memory JF - Neural computationNeural computation Y1 - 1995 A1 - Ruppin, E. A1 - Reggia, James A. VL - 7 ER - TY - JOUR T1 - Polynomial-time algorithm for computing translocation distance between genomes JF - Combinatorial Pattern MatchingCombinatorial Pattern Matching Y1 - 1995 A1 - Sridhar Hannenhalli PB - Springer ER - TY - BOOK T1 - Reversals do not cut long strips Y1 - 1995 A1 - Sridhar Hannenhalli A1 - Pevzner, P. A. PB - Pennsylvania State University, Department of Computer Science and Engineering, College of Engineering ER - TY - JOUR T1 - Sampling properties of DNA sequence data in phylogenetic analysis JF - Mol Biol EvolMol Biol Evol Y1 - 1995 A1 - Michael P. Cummings A1 - Otto, S. P. A1 - Wakeley, J. AB - We inferred phylogenetic trees from individual genes and random samples of nucleotides from the mitochondrial genomes of 10 vertebrates and compared the results to those obtained by analyzing the whole genomes. Individual genes are poor samples in that they infrequently lead to the whole-genome tree. A large number of nucleotide sites is needed to exactly determine the whole-genome tree. A relatively small number of sites, however, often results in a tree close to the whole-genome tree. We found that blocks of contiguous sites were less likely to lead to the whole-genome tree than samples composed of sites drawn individually from throughout the genome. Samples of contiguous sites are not representative of the entire genome, a condition that violates a basic assumption of the bootstrap method as it is applied in phylogenetic studies. VL - 12 ER - TY - CHAP T1 - Towards a computational theory of genome rearrangements T2 - Computer Science TodayComputer Science Today Y1 - 1995 A1 - Sridhar Hannenhalli A1 - Pevzner, Pavel ED - van Leeuwen, Jan AB - Analysis of genome rearrangements in molecular biology started in the late 1930's, when Dobzhansky and Sturtevant published a milestone paper presenting a rearrangement scenario with 17 inversions for the species of Drosophila. However, until recently there were no computer science results allowing a biologist to analyze genome rearrangements. The paper describes combinatorial problems motivated by genome rearrangements, surveys recently developed algorithms for genomic sequence comparison and presents applications of these algorithms to analyze rearrangements in herpes viruses, plant organelles, and mammalian chromosomes. JA - Computer Science TodayComputer Science Today T3 - Lecture Notes in Computer Science PB - Springer Berlin / Heidelberg VL - 1000 SN - 978-3-540-60105-0 ER - TY - Generic T1 - Transforming cabbage into turnip: polynomial algorithm for sorting signed permutations by reversals T2 - Proceedings of the twenty-seventh annual ACM symposium on Theory of computing Y1 - 1995 A1 - Sridhar Hannenhalli A1 - Pevzner, Pavel JA - Proceedings of the twenty-seventh annual ACM symposium on Theory of computing T3 - STOC '95 PB - ACM CY - New York, NY, USA SN - 0-89791-718-9 ER - TY - THES T1 - Transforming men into mice (a computational theory of genome rearrangements) Y1 - 1995 A1 - Sridhar Hannenhalli PB - The Pennsylvania State University ER - TY - Generic T1 - Transforming men into mice (polynomial algorithm for genomic distance problem) T2 - Foundations of Computer Science, Annual IEEE Symposium on Y1 - 1995 A1 - Sridhar Hannenhalli A1 - Pevzner, P. A. KW - biology computing KW - combinatorial properties KW - comparative physical mapping data KW - computable parameters KW - duality (mathematics) KW - duality theorem KW - evolution (biological) KW - Genetics KW - genome rearrangement algorithm KW - genomic distance problem KW - genomic rearrangements KW - human-mouse evolution KW - mammalian evolution KW - multi chromosomal genomes KW - parsimonious rearrangement scenarios KW - pattern matching KW - polynomial algorithm KW - polynomial time algorithm KW - set theory KW - sorting KW - string matching KW - strings KW - zoo fish AB - Many people believe that transformations of humans into mice happen only in fairy tales. However, despite some differences in appearance and habits, men and mice are genetically very similar. In the pioneering paper, J.H. Nadeau and B.A. Taylor (1984) estimated that surprisingly few genomic rearrangements (178/spl plusmn/39) happened since the divergence of human and mouse 80 million years ago. However, their analysis is nonconstructive and no rearrangement scenario for human-mouse evolution has been suggested yet. The problem is complicated by the fact that rearrangements in multi chromosomal genomes include inversions, translocations, fusions and fissions of chromosomes, a rather complex set of operations. As a result, at first glance, a polynomial algorithm for the genomic distance problem with all these operations looks almost as improbable as the transformation of a (real) man into a (real) mouse. We prove a duality theorem which expresses the genomic distance in terms of easily computable parameters reflecting different combinatorial properties of sets of strings. This theorem leads to a polynomial time algorithm for computing most parsimonious rearrangement scenarios. Based on this result and the latest comparative physical mapping data we have constructed a scenario of human-mouse evolution with 131 reversals/translocaitons/fusions/fissions. A combination of the genome rearrangement algorithm with the recently proposed experimental technique called ZOO FISH suggests a new constructive approach to the 100 year old problem of reconstructing mammalian evolution. JA - Foundations of Computer Science, Annual IEEE Symposium on PB - IEEE Computer Society CY - Los Alamitos, CA, USA ER - TY - JOUR T1 - Unsupervised learning of disambiguation rules for part of speech tagging JF - Proceedings of the third workshop on very large corporaProceedings of the third workshop on very large corpora Y1 - 1995 A1 - Brill, E. A1 - M. Pop PB - Somerset, New Jersey: Association for Computational Linguistics VL - 30 ER - TY - JOUR T1 - Identification of the calcium-binding protein calgranulin in the matrix of struvite stones JF - Journal of endourology / Endourological SocietyJournal of endourology / Endourological Society Y1 - 1994 A1 - Bennett, J. A1 - Dretler, S. P. A1 - J. Selengut A1 - Orme-Johnson, W. H. KW - Amino Acid Sequence KW - Calcium-Binding Proteins KW - Cell Adhesion Molecules, Neuronal KW - Electrophoresis KW - Enzyme-Linked Immunosorbent Assay KW - HUMANS KW - Kidney Calculi KW - Leukocyte L1 Antigen Complex KW - Magnesium Compounds KW - Molecular Sequence Data KW - Phosphates AB - The identification of calcium-binding proteins in urine and kidney stones has led to a closer look at the role of matrix proteins in urolithiasis. We analyzed five struvite stones for protein content and identified two bands (8 and 14 KDa) that were confirmed by gel electrophoresis and amino acid sequencing to be calgranulin. This protein, which is known by several other names, has bacteriostatic antifungal activity. Its role in the formation of struvite stones warrants further investigation. VL - 8 N1 - http://www.ncbi.nlm.nih.gov/pubmed/8061680?dopt=Abstract ER - TY - JOUR T1 - P element-mediated in vivo deletion analysis of white-apricot: deletions between direct repeats are strongly favored. JF - Genetics Y1 - 1994 A1 - Kurkulos, M A1 - Weinberg, J M A1 - Roy, D A1 - Mount, S M KW - Alleles KW - Animals KW - Animals, Genetically Modified KW - Base Sequence KW - Crosses, Genetic KW - DNA KW - DNA Transposable Elements KW - Drosophila KW - Eye Color KW - Female KW - Genes, Insect KW - Male KW - Molecular Sequence Data KW - Nucleotidyltransferases KW - PHENOTYPE KW - Recombination, Genetic KW - Repetitive Sequences, Nucleic Acid KW - Sequence Deletion KW - Transformation, Genetic KW - Transposases AB -

We have isolated and characterized deletions arising within a P transposon, P[hswa], in the presence of P transposase. P[hswa] carries white-apricot (wa) sequences, including a complete copia element, under the control of an hsp70 promoter, and resembles the original wa allele in eye color phenotype. In the presence of P transposase, P[hswa] shows a high overall rate (approximately 3%) of germline mutations that result in increased eye pigmentation. Of 234 derivatives of P[hswa] with greatly increased eye pigmentation, at least 205 carried deletions within copia. Of these, 201 were precise deletions between the directly repeated 276-nucleotide copia long terminal repeats (LTRs), and four were unique deletions. High rates of transposase-induced precise deletion were observed within another P transposon carrying unrelated 599 nucleotide repeats (yeast 2 mu FLP; recombinase target sites) separated by 5.7 kb. Our observation that P element-mediated deletion formation occurs preferentially between direct repeats suggests general methods for controlling deletion formation.

VL - 136 CP - 3 ER - TY - Generic T1 - A SIMD solution to the sequence comparison problem on the MGAP T2 - International Conference on Application Specific Array Processors, 1994. Proceedings Y1 - 1994 A1 - Borah, M. A1 - Bajwa, R. S. A1 - Sridhar Hannenhalli A1 - Irwin, M. J. KW - AT-optimal algorithm KW - Biological information theory KW - biology computing KW - biosequence comparison problem KW - computational complexity KW - Computer science KW - Costs KW - database size KW - Databases KW - DNA computing KW - dynamic programming KW - dynamic programming algorithms KW - fine-grained massively parallel processor array KW - Genetics KW - Heuristic algorithms KW - maximally similar sequence KW - MGAP parallel computer KW - Micro-Grain Array Processor KW - Military computing KW - molecular biology KW - molecular biophysics KW - Nearest neighbor searches KW - nearest-neighbor connections KW - Parallel algorithms KW - pipeline processing KW - pipelined SIMD solution KW - sequence alignment problem KW - sequences AB - Molecular biologists frequently compare an unknown biosequence with a set of other known biosequences to find the sequence which is maximally similar, with the hope that what is true of one sequence, either physically or functionally, could be true of its analogue. Even though efficient dynamic programming algorithms exist for the problem, when the size of the database is large, the time required is quite long, even for moderate length sequences. In this paper, we present an efficient pipelined SIMD solution to the sequence alignment problem on the Micro-Grain Array Processor (MGAP), a fine-grained massively parallel array of processors with nearest-neighbor connections. The algorithm compares K sequences of length O(M) with the actual sequence of length N, in O(M+N+K) time with O(MN) processors, which is AT-optimal. The implementation on the MGAP computes at the rate of about 0.1 million comparisons per second for sequences of length 128 JA - International Conference on Application Specific Array Processors, 1994. Proceedings PB - IEEE SN - 0-8186-6517-3 ER - TY - JOUR T1 - Slipped-strand mispairing in a plastid gene: ıt rpoC2 in grasses (Poaceae) JF - Mol Biol EvolMol Biol Evol Y1 - 1994 A1 - Michael P. Cummings A1 - King, L. M. A1 - Kellogg, E. A. AB - An exception to the generally conservative nature of plastid gene evolution is the gene coding for the beta" subunit of RNA polymerase, rpoC2. Previous work by others has shown that maize and rice have an insertion in the coding region of rpoC2, relative to spinach and tobacco. To assess the distribution of this extra coding sequence, we surveyed a broad phylogenetic sample comprising 55 species from 17 angiosperm families by using Southern hybridization. The extra coding sequence is restricted to the grasses (Poaceae). DNA sequence analysis of 11 species from all five subfamilies within the grass family demonstrates that the extra sequence in the coding region of rpoC2 is a repetitive array that exhibits more than a twofold increase in nucleotide substitution, as well as a large number of insertion/deletion events, relative to the adjacent flanking sequences. The structure of the array suggests that slipped-strand mispairing causes the repeated motifs and adds to the mechanisms through which the coding sequence of plastid genes are known to evolve. Phylogenetic analyses based on the sequence data from grass species support several relationships previously suggested by morphological work, but they are ambiguous about broad relationships within the family. VL - 11 ER - TY - JOUR T1 - Suppressor U1 snRNAs in Drosophila. JF - Genetics Y1 - 1994 A1 - Lo, P C A1 - Roy, D A1 - Mount, S M KW - Alternative Splicing KW - Animals KW - Base Sequence KW - Cell Line KW - Cell Nucleus KW - DNA Primers KW - Drosophila melanogaster KW - Female KW - Genes, Suppressor KW - Genetic Variation KW - GENOTYPE KW - Introns KW - Male KW - Molecular Sequence Data KW - Mutagenesis, Site-Directed KW - Nucleic Acid Conformation KW - Oligodeoxyribonucleotides KW - PHENOTYPE KW - Recombinant Proteins KW - Ribonucleoprotein, U1 Small Nuclear KW - RNA, Small Nuclear KW - Transfection KW - Transformation, Genetic AB -

Although the role of U1 small nuclear RNAs (snRNAs) in 5' splice site recognition is well established, suppressor U1 snRNAs active in intact multicellular animals have been lacking. Here we describe suppression of a 5' splice site mutation in the Drosophila melanogaster white gene (wDR18) by compensatory changes in U1 snRNA. Mutation of positions -1 and +6 of the 5' splice site of the second intron (ACG[GTGAGT to ACC]GTGAGC) results in the accumulation of RNA retaining this 74-nucleotide intron in both transfected cells and transgenic flies. U1-3G, a suppressor U1 snRNA which restores base-pairing at position +6 of the mutant intron, increases the ratio of spliced to unspliced wDR18 RNA up to fivefold in transfected Schneider cells and increases eye pigmentation in wDR18 flies. U1-9G, which targets position -1, suppresses wDR18 in transfected cells less well. U1-3G,9G has the same effect as U1-3G although it accumulates to lower levels. Suppression of wDR18 has revealed that the U1b embryonic variant (G134 to U) is active in Schneider cells and pupal eye discs. However, the combination of 9G with 134U leads to reduced accumulation of both U1b-9G and U1b-3G,9G, possibly because nucleotides 9 and 134 both participate in a potential long-range intramolecular base-pairing interaction. High levels of functional U1-3G suppressor reduce both viability and fertility in transformed flies. These results show that, despite the difficulties inherent in stably altering splice site selection in multicellular organisms, it is possible to obtain suppressor U1 snRNAs in flies.

VL - 138 CP - 2 ER - TY - JOUR T1 - Transmission patterns of eukaryotic transposable elements - arguments for and against horizontal transfer JF - Trends Ecol EvolTrends Ecol Evol Y1 - 1994 A1 - Michael P. Cummings AB - Recent studies have demonstrated that several classes of transposable elements are widely distributed within eukaryotes. Horizontal transmission of these transposable elements has often been invoked in order to explain the observed variation and relationships within and between species. These same patterns of variation and relationships, however, may originate from processes that do not involve the lateral transfer of genetic material across species. VL - 9 ER - TY - Generic T1 - A distributed algorithm for ear decomposition T2 - Fifth International Conference on Computing and Information, 1993. Proceedings ICCI '93 Y1 - 1993 A1 - Sridhar Hannenhalli A1 - Perumalla, K. A1 - Chandrasekharan, N. A1 - Sridhar, R. KW - Asynchronous communication KW - asynchronous communication network KW - Automata KW - Communication networks KW - computational complexity KW - Computer networks KW - Computer science KW - decomposition graph KW - distributed algorithm KW - distributed algorithms KW - Distributed computing KW - Ear KW - ear decomposition KW - graph theory KW - message-optimal KW - network decomposition KW - sorting KW - Testing KW - time-optimal AB - A distributed algorithm for finding an ear decomposition of an asynchronous communication network with n nodes and m links is presented. At the completion of the algorithm either the ears are correctly labeled or the nodes are informed that there exists no ear decomposition. First we present a novel algorithm to check the existence of an ear decomposition which uses O(m) messages. We also present two other algorithms, one which is time-optimal and the other which is message-optimal to determine the actual ears and their corresponding numbers after determining the existence of an ear decomposition JA - Fifth International Conference on Computing and Information, 1993. Proceedings ICCI '93 PB - IEEE SN - 0-8186-4212-2 ER - TY - JOUR T1 - Gene organization: nested genes take flight. JF - Curr Biol Y1 - 1993 A1 - Mount, S A1 - Henikoff, S VL - 3 CP - 6 ER - TY - JOUR T1 - Species-specific signals for the splicing of a short Drosophila intron in vitro. JF - Mol Cell Biol Y1 - 1993 A1 - Guo, M A1 - Lo, P C A1 - Mount, S M KW - Animals KW - Base Sequence KW - Cell Nucleus KW - Consensus Sequence KW - DNA KW - DNA Transposable Elements KW - Drosophila KW - Drosophila Proteins KW - Electrophoresis, Polyacrylamide Gel KW - HeLa Cells KW - HUMANS KW - Introns KW - Molecular Sequence Data KW - Mutation KW - Peptide Hydrolases KW - Proteins KW - Regulatory Sequences, Nucleic Acid KW - Retroelements KW - RNA Splicing KW - Species Specificity AB -

The effects of branchpoint sequence, the pyrimidine stretch, and intron size on the splicing efficiency of the Drosophila white gene second intron were examined in nuclear extracts from Drosophila and human cells. This 74-nucleotide intron is typical of many Drosophila introns in that it lacks a significant pyrimidine stretch and is below the minimum size required for splicing in human nuclear extracts. Alteration of sequences of adjacent to the 3' splice site to create a pyrimidine stretch was necessary for splicing in human, but not Drosophila, extracts. Increasing the size of this intron with insertions between the 5' splice site and the branchpoint greatly reduced the efficiency of splicing of introns longer than 79 nucleotides in Drosophila extracts but had an opposite effect in human extracts, in which introns longer than 78 nucleotides were spliced with much greater efficiency. The white-apricot copia insertion is immediately adjacent to the branchpoint normally used in the splicing of this intron, and a copia long terminal repeat insertion prevents splicing in Drosophila, but not human, extracts. However, a consensus branchpoint does not restore the splicing of introns containing the copia long terminal repeat, and alteration of the wild-type branchpoint sequence alone does not eliminate splicing. These results demonstrate species specificity of splicing signals, particularly pyrimidine stretch and size requirements, and raise the possibility that variant mechanisms not found in mammals may operate in the splicing of small introns in Drosophila and possibly other species.

VL - 13 CP - 2 ER - TY - JOUR T1 - copia-like retrotransposons are ubiquitous among plants JF - Proc Natl Acad Sci USAProc Natl Acad Sci USA Y1 - 1992 A1 - Voytas, D. F. A1 - Michael P. Cummings A1 - Koniczny, A. A1 - Ausubel, F. M. A1 - Rodermel, S. R. AB - Transposable genetic elements are assumed to be a feature of all eukaryotic genomes. Their identification, however, has largely been haphazard, limited principally to organisms subjected to molecular or genetic scrutiny. We assessed the phylogenetic distribution of copia-like retrotransposons, a class of transposable element that proliferates by reverse transcription, using a polymerase chain reaction assay designed to detect copia-like element reverse transcriptase sequences. copia-like retrotransposons were identified in 64 plant species as well as the photosynthetic protist Volvox carteri. The plant species included representatives from 9 of 10 plant divisions, including bryophytes, lycopods, ferns, gymnosperms, and angiosperms. DNA sequence analysis of 29 cloned PCR products and of a maize retrotransposon cDNA confirmed the identity of these sequences as copia-like reverse transcriptase sequences, thereby demonstrating that this class of retrotransposons is a ubiquitous component of plant genomes. VL - 89 ER - TY - JOUR T1 - Copia-like retrotransposons in plants: a brief introduction JF - The Plant Genetics NewsletterThe Plant Genetics Newsletter Y1 - 1992 A1 - Michael P. Cummings VL - 8 ER - TY - Generic T1 - Efficient algorithms for computing matching and chromatic polynomials on series-parallel graphs T2 - Fourth International Conference on Computing and Information, 1992. Proceedings. ICCI '92 Y1 - 1992 A1 - Chandrasekharan, N. A1 - Sridhar Hannenhalli KW - chromatic polynomials KW - computational complexity KW - Computer science KW - graph colouring KW - graph theory KW - matching polynomial KW - Polynomials KW - series-parallel graphs KW - Terminology KW - Tree data structures KW - Tree graphs AB - The authors present efficient algorithms for computing the matching polynomial and chromatic polynomial of a series-parallel graph in O(n3) and O(n2) time respectively. Their algorithm for computing the matching polynomial generalizes an existing result from Lovasz, Plummer (1986) and the chromatic polynomial algorithm improves the result given by Hunt, Ravi, Stearn (1988) from O(n4) time JA - Fourth International Conference on Computing and Information, 1992. Proceedings. ICCI '92 PB - IEEE SN - 0-8186-2812-X ER - TY - JOUR T1 - Patterns and processes of sequence evolution: plant organelle genomes and copia-like retrotransposons Y1 - 1992 A1 - Michael P. Cummings ER - TY - JOUR T1 - Splicing signals in Drosophila: intron size, information content, and consensus sequences. JF - Nucleic Acids Res Y1 - 1992 A1 - Mount, S M A1 - Burks, C A1 - Hertz, G A1 - Stormo, G D A1 - White, O A1 - Fields, C KW - Animals KW - Base Sequence KW - Consensus Sequence KW - Databases, Factual KW - Drosophila KW - Introns KW - Molecular Sequence Data KW - RNA Splicing KW - RNA, Messenger KW - software AB -

A database of 209 Drosophila introns was extracted from Genbank (release number 64.0) and examined by a number of methods in order to characterize features that might serve as signals for messenger RNA splicing. A tight distribution of sizes was observed: while the smallest introns in the database are 51 nucleotides, more than half are less than 80 nucleotides in length, and most of these have lengths in the range of 59-67 nucleotides. Drosophila splice sites found in large and small introns differ in only minor ways from each other and from those found in vertebrate introns. However, larger introns have greater pyrimidine-richness in the region between 11 and 21 nucleotides upstream of 3' splice sites. The Drosophila branchpoint consensus matrix resembles C T A A T (in which branch formation occurs at the underlined A), and differs from the corresponding mammalian signal in the absence of G at the position immediately preceding the branchpoint. The distribution of occurrences of this sequence suggests a minimum distance between 5' splice sites and branchpoints of about 38 nucleotides, and a minimum distance between 3' splice sites and branchpoints of 15 nucleotides. The methods we have used detect no information in exon sequences other than in the few nucleotides immediately adjacent to the splice sites. However, Drosophila resembles many other species in that there is a discontinuity in A + T content between exons and introns, which are A + T rich.

VL - 20 CP - 16 ER - TY - Generic T1 - Parallel transitive closure computations using topological sort T2 - Proceedings of the First International Conference on Parallel and Distributed Information Systems, 1991 Y1 - 1991 A1 - Hua, K. A. A1 - Sridhar Hannenhalli KW - Computer science KW - Concurrent computing KW - data partitioning KW - Database systems KW - database theory KW - deductive databases KW - File systems KW - horizontal partitioning KW - joins KW - local data fragments KW - message passing multiprocessor system KW - Multiprocessing systems KW - Parallel algorithms KW - PARALLEL PROCESSING KW - parallel programming KW - parallel transitive closure KW - processing nodes KW - relation tuples KW - Relational databases KW - sorting KW - topological sort AB - Deals with parallel transitive closure computations. The sort-based approaches introduced sorts the tuples of the relation into topological order, and the sorted relation is then horizontally partitioned and distributed across several processing nodes of a message passing multiprocessor system. This data partitioning strategy allows the transitive closure computation of the local data fragments to be computed in parallel with no interprocessor communication. The construction of the final result then requires only a small number of joins. Extensive analytical results are included in the paper as well. They show that the proposed techniques leads to a speedup that is essentially linear with the number of processors. Its performance is significantly better than the recently published hashless parallel algorithm JA - Proceedings of the First International Conference on Parallel and Distributed Information Systems, 1991 PB - IEEE SN - 0-8186-2295-4 ER - TY - JOUR T1 - Polyadenylylation in copia requires unusually distant upstream sequences. JF - Proc Natl Acad Sci U S A Y1 - 1991 A1 - Kurkulos, M A1 - Weinberg, J M A1 - Pepling, M E A1 - Mount, S M KW - Animals KW - Base Sequence KW - Blotting, Northern KW - DNA Transposable Elements KW - Drosophila melanogaster KW - Eye Color KW - Molecular Sequence Data KW - Oligonucleotides KW - Polymerase Chain Reaction KW - Regulatory Sequences, Nucleic Acid KW - Repetitive Sequences, Nucleic Acid KW - RNA Processing, Post-Transcriptional KW - RNA, Messenger AB -

Retroviruses and related genetic elements generate terminally redundant RNA products by differential polyadenylylation within a long terminal repeat. Expression of the white-apricot (wa) allele of Drosophila melanogaster, which carries an insertion of the 5.1-kilobase retrovirus-like transposable element copia in a small intron, is influenced by signals within copia. By using this indicator, we have isolated a 518-base-pair deletion, 312 base pairs upstream of the copia polyadenylylation site, that is phenotypically like much larger deletions and eliminates RNA species polyadenylylated in copia. This requirement of distant upstream sequences for copia polyadenylylation has implications for the expression of many genetic elements bearing long terminal repeats.

VL - 88 CP - 8 ER - TY - JOUR T1 - Review of Fundamentals of Molecular Evolution, by Li. W.-H. and D. Graur JF - CladisticsCladistics Y1 - 1991 A1 - Michael P. Cummings VL - 7 ER - TY - JOUR T1 - A superfamily of ıt Arabidopsis thaliana retrotransposons JF - GeneticsGenetics Y1 - 1991 A1 - Konieczny, A. A1 - Voytas, D. F. A1 - Michael P. Cummings A1 - Ausubel, F. M. AB - We describe a superfamily of Arabidopsis thaliana retrotransposable elements that consists of at least ten related families designated Ta1-Ta10. The Ta1 family has been described previously. Two genomic clones representing the Ta2 and Ta3 elements were isolated from an A. thaliana (race Landsberg erecta) lambda library using sequences derived from the reverse transcriptase region of Ta1 as hybridization probes. Nucleotide sequence analysis showed that the Ta1, Ta2 and Ta3 families share greater than 75% amino acid identity in pairwise comparisons of their reverse transcriptase and RNase H genes. In addition to Ta1, Ta2 and Ta3, we identified seven other related retrotransposon families in Landsberg erecta, Ta4-Ta10, using degenerate primers and the polymerase chain reaction to amplify a highly conserved region of retrotransposon-encoded reverse transcriptase. One to two copies of elements Ta2-Ta10 are present in the genomes of the A. thaliana races Landsberg erecta and Columbia indicating that the superfamily comprises at least 0.1% of the A. thaliana genome. The nucleotide sequences of the reverse transcriptase regions of the ten element families place them in the category of copia-like retrotransposons and phylogenetic analysis of the amino acid sequences suggests that horizontal transfer may have played a role in their evolution. VL - 127 ER - TY - JOUR T1 - Characterization of enhancer-of-white-apricot in Drosophila melanogaster. JF - Genetics Y1 - 1990 A1 - Peng, X B A1 - Mount, S M KW - Alleles KW - Animals KW - Blotting, Northern KW - DNA Transposable Elements KW - Drosophila melanogaster KW - Eye Color KW - Female KW - Heterozygote KW - Homozygote KW - Male KW - Nucleic Acid Hybridization KW - PHENOTYPE KW - Poly A KW - Reproduction KW - RNA KW - RNA, Messenger KW - Transcription, Genetic AB -

The white-apricot (wa) allele differs from the wild-type white gene by the presence of the retrovirus-like transposable element copia within the transcription unit. Most RNAs derived from wa have 3' termini within this insertion, and only small amounts of structurally normal RNA are produced. The activity of wa is reduced in trans by a semidominant mutation in the gene Enhancer-of-white-apricot (E(wa). Flies that are wa and heterozygous for the enhancer have eyes which are much lighter than the orange-yellow of wa alone while E(wa) homozygotes have white eyes. This semidominant effect on pigmentation is correlated with a corresponding decrease in white RNA having wild type structure, and flies homozygous for E(wa) have increased levels of aberrant RNAs. Three reverant alleles of E(wa) generated by reversion of the dominant enhancer phenotype with gamma radiation are noncomplementing recessive lethals, with death occurring during the larval stage. The effects on wa eye pigmentation of varying doses of the original E(wa) allele, the wild type allele, and the revertant alleles suggest that the original E(wa) allele produces a product that interferes with the activity of the wild type gene and that the revertants are null alleles. We propose that the E(wa) gene product influences the activity of the downstream copia long terminal repeat in 3' end formation.

VL - 126 CP - 4 ER - TY - JOUR T1 - Drosophila melanogaster genes for U1 snRNA variants and their expression during development. JF - Nucleic Acids Res Y1 - 1990 A1 - Lo, P C A1 - Mount, S M KW - Animals KW - Base Sequence KW - Blotting, Southern KW - Cloning, Molecular KW - Drosophila melanogaster KW - Gene Expression Regulation KW - genes KW - Genetic Variation KW - Molecular Sequence Data KW - Nucleic Acid Conformation KW - Pseudogenes KW - Restriction Mapping KW - RNA, Small Nuclear AB -

We have cloned and characterized a complete set of seven U1-related sequences from Drosophila melanogaster. These sequences are located at the three cytogenetic loci 21D, 82E, and 95C. Three of these sequences have been previously studied: one U1 gene at 21D which encodes the prototype U1 sequence (U1a), one U1 gene at 82E which encodes a U1 variant with a single nucleotide substitution (U1b), and a pseudogene at 82E. The four previously uncharacterized genes are another U1b gene at 82E, two additional U1a genes at 95C, and a U1 gene at 95C which encodes a new variant (U1c) with a distinct single nucleotide change relative to U1a. Three blocks of 5' flanking sequence similarity are common to all six full length genes. Using specific primer extension assays, we have observed that the U1b RNA is expressed in Drosophila Kc cells and is associated with snRNP proteins, suggesting that the U1b-containing snRNP particles are able to participate in the process of pre-mRNA splicing. We have also examined the expression throughout Drosophila development of the two U1 variants relative to the prototype sequence. The U1c variant is undetectable by our methods, while the U1b variant exhibits a primarily embryonic pattern reminiscent of the expression of certain U1 variants in sea urchin, Xenopus, and mouse.

VL - 18 CP - 23 ER - TY - JOUR T1 - Evolution of avocados as revealed by DNA restriction fragment variation JF - J HeredJ Hered Y1 - 1990 A1 - Furnier, G. R. A1 - Michael P. Cummings A1 - Clegg, M. T. AB - Individuals representing the genus ıt Persea, subgenus ıt Persea were assayed for restriction fragment length polymorphisms in their chloroplast genome, nuclear ribosomal DNA, and the genes coding for the enzyme cellulase. The subgenus ıt Persea appears to consist of ıt P. schiedeana and a separate taxon containing the remaining species. ıt P. americana does not appear to be a monophyletic group. If ıt P. americana is to be maintained as a species containing var. ıt americana, var. ıt drymifolia, and var. ıt guatemalensis, then our data suggest that it should also contain varieties corresponding to ıt P. floccosa, ıt P. nubigena, and ıt P. steyermarkii. ıt P. americana var. ıt guatemalensis appears to have originated as a hybrid between ıt P. steyermarkii and ıt P. nubigena. The root-rot-resistant cultivar G755A is a hybrid progeny of ıt P. schiedeana and ıt P. americana var. guatemalensis. The three varieties of ıt P. americana were all distinguished by mutations. VL - 81 ER - TY - JOUR T1 - Sequence of a cDNA from the Drosophila melanogaster white gene. JF - Nucleic Acids Res Y1 - 1990 A1 - Pepling, M A1 - Mount, S M KW - Amino Acid Sequence KW - Animals KW - Base Sequence KW - DNA KW - Drosophila melanogaster KW - Eye Color KW - genes KW - Molecular Sequence Data VL - 18 CP - 6 ER - TY - JOUR T1 - Structure and expression of the Drosophila melanogaster gene for the U1 small nuclear ribonucleoprotein particle 70K protein. JF - Mol Cell Biol Y1 - 1990 A1 - Mancebo, R A1 - Lo, P C A1 - Mount, S M KW - Amino Acid Sequence KW - Animals KW - Base Sequence KW - Blotting, Northern KW - Blotting, Southern KW - Cloning, Molecular KW - DNA KW - Drosophila melanogaster KW - Gene expression KW - Gene Library KW - genes KW - HUMANS KW - Molecular Sequence Data KW - Molecular Weight KW - Oligonucleotide Probes KW - Poly A KW - Ribonucleoproteins KW - Ribonucleoproteins, Small Nuclear KW - RNA KW - RNA, Messenger KW - Sequence Homology, Nucleic Acid KW - Xenopus AB -

A genomic clone encoding the Drosophila U1 small nuclear ribonucleoprotein particle 70K protein was isolated by hybridization with a human U1 small nuclear ribonucleoprotein particle 70K protein cDNA. Southern blot and in situ hybridizations showed that this U1 70K gene is unique in the Drosophila genome, residing at cytological position 27D1,2. Polyadenylated transcripts of 1.9 and 3.1 kilobases were observed. While the 1.9-kilobase mRNA is always more abundant, the ratio of these two transcripts is developmentally regulated. Analysis of cDNA and genomic sequences indicated that these two RNAs encode an identical protein with a predicted molecular weight of 52,879. Comparison of the U1 70K proteins predicted from Drosophila, human, and Xenopus cDNAs revealed 68% amino acid identity in the most amino-terminal 214 amino acids, which include a sequence motif common to many proteins which bind RNA. The carboxy-terminal half is less well conserved but is highly charged and contains distinctive arginine-rich regions in all three species. These arginine-rich regions contain stretches of arginine-serine dipeptides like those found in transformer, transformer-2, and suppressor-of-white-apricot proteins, all of which have been identified as regulators of mRNA splicing in Drosophila melanogaster.

VL - 10 CP - 6 ER - TY - JOUR T1 - The structure, distribution and evolution of the ıt Ta1 retrotransposable element family of ıt Arabidopsis thaliana JF - GeneticsGenetics Y1 - 1990 A1 - Voytas, D. F. A1 - Konieczny, A. A1 - Michael P. Cummings A1 - Ausubel, F. M. AB - The Ta1 elements are a low copy number, copia-like retrotransposable element family of Arabidopsis thaliana. Six Ta1 insertions comprise all of the Ta1 element copies found in three geographically diverse A. thaliana races. These six elements occupy three distinct target sites: Ta1-1 is located on chromosome 5 and is common to all three races (Col-0, Kas-1 and La-0). Ta1-2 is present in two races on chromosome 4 (Kas-1 and La-0), and Ta1-3, also located on chromosome 4, is present only in one race (La-0). The six Ta1 insertions share greater than 96% nucleotide identity, yet are likely to be incapable of further transposition due to deletions or nucleotide changes that alter either the coding capacity of the elements or conserved protein domains required for retrotransposition. Nucleotide sequence comparisons of these elements and the distribution of Ta1 among 12 additional A. thaliana geographical races suggest that Ta1-1 predated the global dispersal of A. thaliana. As the species spread throughout the world, two additional transposition events occurred which gave rise first to Ta1-2 and finally to Ta1-3. VL - 126 ER - TY - JOUR T1 - Management of an enlarging aortic aneurysm in the presence of radiation induced retroperitoneal fibrosis. JF - J Cardiovasc Surg (Torino) Y1 - 1989 A1 - Todd, G J A1 - Schwartz, A A1 - Rapoport, F KW - Aged KW - Aorta, Abdominal KW - Aortic Aneurysm KW - Blood Vessel Prosthesis KW - HUMANS KW - Lymphoma KW - Male KW - Radiation Injuries KW - Retroperitoneal Fibrosis KW - Retroperitoneal Neoplasms KW - T-Lymphocytes AB -

Despite a thoracoabdominal retroperitoneal approach to an enlarging symptomatic infrarenal aortic aneurysm, proximal aortic dissection was hazardous due to radiation induced retroperitoneal fibrosis. Iliac artery ligation and thoracic aorta to iliac artery bypass has resulted in successful management during 14 months of follow-up.

VL - 30 CP - 2 ER - TY - JOUR T1 - Partial revertants of the transposable element-associated suppressible allele white-apricot in Drosophila melanogaster: structures and responsiveness to genetic modifiers. JF - Genetics Y1 - 1988 A1 - Mount, S M A1 - Green, M M A1 - Rubin, G M KW - Alleles KW - Animals KW - Base Sequence KW - DNA Transposable Elements KW - Drosophila melanogaster KW - Enhancer Elements, Genetic KW - GENOTYPE KW - Molecular Sequence Data KW - Mutation KW - Suppression, Genetic AB -

The eye color phenotype of white-apricot (wa), a mutant allele of the white locus caused by the insertion of the transposable element copia into a small intron, is suppressed by the extragenic suppressor suppressor-of-white-apricot (su(wa] and enhanced by the extragenic enhancers suppressor-of-forked su(f] and Enhancer-of-white-apricot (E(wa]. Derivatives of wa have been analyzed molecularly and genetically in order to correlate the structure of these derivatives with their response to modifiers. Derivatives in which the copia element is replaced precisely by a solo long terminal repeat (sLTR) were generated in vitro and returned to the germline by P-element mediated transformation; flies carrying this allele within a P transposon show a nearly wild-type phenotype and no response to either su(f) or su(wa). In addition, eleven partial phenotypic revertants of wa were analyzed. Of these, one appears to be a duplication of a large region which includes wa, three are new alleles of su(wa), two are sLTR derivatives whose properties confirm results obtained using transformation, and five are secondary insertions into the copia element within wa. One of these, waR84h, differs from wa by the insertion of the most 3' 83 nucleotides of the I factor. The five insertion derivatives show a variety of phenotypes and modes of interaction with su[f) and su(wa). The eye pigmentation of waR84h is affected by su(f) and E(wa), but not su(wa). These results demonstrate that copia (as opposed to the interruption of white sequences) is essential for the wa phenotype and its response to genetic modifiers, and that there are multiple mechanisms for the alteration of the wa phenotype by modifiers.

VL - 118 CP - 2 ER - TY - JOUR T1 - Sequence similarity. JF - Nature Y1 - 1987 A1 - Mount, S M KW - Adenosine Triphosphate KW - Amino Acid Sequence KW - Animals KW - Bacterial Proteins KW - Biological Transport, Active KW - Carrier Proteins KW - Drosophila melanogaster KW - genes KW - HUMANS KW - Pigments, Biological KW - Sequence Homology, Nucleic Acid VL - 325 CP - 6104 M3 - 10.1038/325487c0 ER - TY - JOUR T1 - Complete nucleotide sequence of the Drosophila transposable element copia: homology between copia and retroviral proteins. JF - Mol Cell Biol Y1 - 1985 A1 - Mount, S M A1 - Rubin, G M KW - Amino Acid Sequence KW - Animals KW - Base Sequence KW - Codon KW - DNA Helicases KW - DNA Transposable Elements KW - Drosophila melanogaster KW - Gene Expression Regulation KW - Gene Products, gag KW - Integrases KW - Repetitive Sequences, Nucleic Acid KW - Retroviridae KW - RNA-Directed DNA Polymerase KW - Viral Envelope Proteins KW - Viral Proteins AB -

We have determined the complete nucleotide sequence of the copia element present at the white-apricot allele of the white locus in Drosophila melanogaster. This transposable element is 5,146 nucleotides long and contains a single long open reading frame of 4,227 nucleotides. Analysis of the coding potential of the large open reading frame, which appears to encode a polyprotein, revealed weak homology to a number of retroviral proteins, including a protease, nucleic acid-binding protein, and reverse transcriptase. Better homology existed between another part of the copia open reading frame and a region of the retroviral pol gene recently shown to be distinct from reverse transcriptase and required for the integration of circular DNA forms of the retroviral genome to form proviruses. Comparison of the copia sequence with those of the Saccharomyces cerevisiae transposable element Ty, several vertebrate retroviruses, and the D. melanogaster copia-like element 17.6 showed that Ty was most similar to copia, sharing amino acid sequence homology and organizational features not found in the other genetic elements.

VL - 5 CP - 7 ER - TY - JOUR T1 - Lessons from mutant globins. JF - Nature Y1 - 1983 A1 - Mount, S A1 - Steitz, J KW - Globins KW - HUMANS KW - Mutation KW - RNA, Messenger KW - Thalassemia KW - Transcription, Genetic VL - 303 CP - 5916 ER - TY - JOUR T1 - Pseudogenes for human small nuclear RNA U3 appear to arise by integration of self-primed reverse transcripts of the RNA into new chromosomal sites. JF - Cell Y1 - 1983 A1 - Bernstein, L B A1 - Mount, S M A1 - Weiner, A M KW - Animals KW - Base Sequence KW - DNA KW - genes KW - HUMANS KW - Nucleic Acid Conformation KW - Rats KW - Recombination, Genetic KW - Repetitive Sequences, Nucleic Acid KW - RNA KW - RNA, Small Nuclear KW - RNA-Directed DNA Polymerase KW - Templates, Genetic KW - Transcription, Genetic AB -

We find that both human and rat U3 snRNA can function as self-priming templates for AMV reverse transcriptase in vitro. The 74 base cDNA is primed by the 3' end of intact U3 snRNA, and spans the characteristically truncated 69 or 70 base U3 sequence found in four different human U3 pseudogenes. The ability of human and rat U3 snRNA to self-prime is consistent with a U3 secondary structure model derived by a comparison between rat U3 snRNA and the homologous D2 snRNA from Dictyostelium discoideum. We propose that U3 pseudogenes are generated in vivo by integration of a self-primed cDNA copy of U3 snRNA at new chromosomal sites. We also consider the possibility that the same cDNA mediates gene conversion at the 5' end of bona fide U3 genes where, over the entire region spanned by the U3 cDNA, the two rat U3 sequence variants U3A and U3B are identical.

VL - 32 CP - 2 ER - TY - JOUR T1 - RNA processing. Sequences that signal where to splice. JF - Nature Y1 - 1983 A1 - Mount, S M KW - Base Sequence KW - RNA Splicing KW - Saccharomyces cerevisiae VL - 304 CP - 5924 ER - TY - JOUR T1 - Small ribonucleoproteins from eukaryotes: structures and roles in RNA biogenesis. JF - Cold Spring Harb Symp Quant Biol Y1 - 1983 A1 - Steitz, J A A1 - Wolin, S L A1 - Rinke, J A1 - Pettersson, I A1 - Mount, S M A1 - Lerner, E A A1 - Hinterberger, M A1 - Gottlieb, E KW - Animals KW - Base Sequence KW - HeLa Cells KW - HUMANS KW - Mice KW - Molecular Weight KW - Nucleic Acid Conformation KW - Nucleic Acid Hybridization KW - Nucleoproteins KW - Ribonucleoproteins KW - Ribonucleoproteins, Small Nuclear KW - RNA Polymerase III KW - Transcription, Genetic VL - 47 Pt 2 ER - TY - JOUR T1 - Splicing of messenger RNA precursors is inhibited by antisera to small nuclear ribonucleoprotein. JF - Cell Y1 - 1983 A1 - Padgett, R A A1 - Mount, S M A1 - Steitz, J A A1 - Sharp, P A KW - Adenoviruses, Human KW - Antigens KW - Autoantigens KW - Base Sequence KW - Cell Extracts KW - HeLa Cells KW - HUMANS KW - Immune Sera KW - Nucleic Acid Precursors KW - Ribonucleoproteins KW - Ribonucleoproteins, Small Nuclear KW - RNA KW - RNA Precursors KW - RNA Splicing KW - RNA, Messenger KW - RNA, Small Cytoplasmic KW - RNA, Viral KW - Transcription, Genetic AB -

A mouse monoclonal antibody and human autoimmune sera directed against various classes of small ribonucleoprotein particles have been tested for inhibition of mRNA splicing in a soluble in vitro system. The splicing of the first and second leader exons of adenovirus late RNA was inhibited only by those sera that reacted with U1 RNP. Both U1 RNP-specific human autoimmune serum and sera directed against the Sm class of small nuclear RNPs, including a mouse monoclonal antibody, specifically inhibited splicing. Antisera specific for U2 RNP had no effect on splicing nor did antisera specific for the La or Ro class of small RNPs. These results suggest that U1 RNP is essential for the splicing of mRNA precursors.

VL - 35 CP - 1 ER - TY - JOUR T1 - The U1 small nuclear RNA-protein complex selectively binds a 5' splice site in vitro. JF - Cell Y1 - 1983 A1 - Mount, S M A1 - Pettersson, I A1 - Hinterberger, M A1 - Karmas, A A1 - Steitz, J A KW - Base Sequence KW - DNA-Directed RNA Polymerases KW - HUMANS KW - Nucleoproteins KW - Ribonuclease T1 KW - Ribonucleoproteins KW - Ribonucleoproteins, Small Nuclear KW - RNA KW - RNA Splicing KW - T-Phages AB -

The ability of purified U1 small nuclear RNA-protein complexes (U1 snRNPs) to bind in vitro to two RNAs transcribed from recombinant DNA clones by bacteriophage T7 RNA polymerase has been studied. A transcript which contains sequences corresponding to the small intron and flanking exons of the major mouse beta-globin gene is bound in marked preference to an RNA devoid of splice site sequences. The site of U1 snRNP binding to the globin RNA has been defined by T1 ribonuclease digestion of the RNA-U1 snRNP complex. A 15-17-nucleotide region, including the 5' splice site, remains undigested and complexed with the snRNP such that it can be co-precipitated by antibodies directed against the U1 snRNP. Partial proteinase K digestion of the U1 snRNP abolishes interaction with the globin RNA, indicating that the snRNP proteins contribute significantly to RNA binding. No RNA cleavage, splicing, or recognition of the 3' splice site by U1 snRNPs has been detected. Our results are discussed in terms of the probable role of U1 snRNPs in the messenger RNA splicing of eucaryotic cell nuclei.

VL - 33 CP - 2 ER - TY - JOUR T1 - A catalogue of splice junction sequences. JF - Nucleic Acids Res Y1 - 1982 A1 - Mount, S M KW - Animals KW - Base Sequence KW - genes KW - Genes, Viral KW - HUMANS KW - Repetitive Sequences, Nucleic Acid KW - RNA Splicing KW - Species Specificity AB -

Splice junction sequences from a large number of nuclear and viral genes encoding protein have been collected. The sequence CAAG/GTAGAGT was found to be a consensus of 139 exon-intron boundaries (or donor sequences) and (TC)nNCTAG/G was found to be a consensus of 130 intron-exon boundaries (or acceptor sequences). The possible role of splice junction sequences as signals for processing is discussed.

VL - 10 CP - 2 ER - TY - JOUR T1 - Structure and function of small ribonucleoproteins from eukaryotic cells. JF - Princess Takamatsu Symp Y1 - 1982 A1 - Steitz, J A A1 - Berg, C A1 - Gottlieb, E A1 - Hardin, J A A1 - Hashimoto, C A1 - Hendrick, J P A1 - Hinterberger, M A1 - Krikeles, M A1 - Lerner, M R A1 - Mount, S M KW - Antigen-Antibody Complex KW - Autoantibodies KW - HUMANS KW - Lupus Erythematosus, Systemic KW - Nucleoproteins KW - Ribonucleoproteins KW - RNA Polymerase III KW - Transcription, Genetic AB -

Autoantibodies from patients with systemic lupus erythematosus and other related diseases have been used to identify and study small RNA-protein complexes from mammalian cells. Properties of three previously described and several new classes of small ribonucleoproteins (RNPs) are reviewed. The sequence of Drosophila U1 RNA reveals that the region proposed to pair with 5' splice junctions is conserved, while that proposed to interact with 3' junctions diverges; this forces some revision of the model for U1 small nuclear (sn)RNP participation in hnRNA splicing. Further characterization of the Ro and La small RNPs has shown that the Ro small cytoplasmic (sc)RNPs are a subclass of La RNPs. Both tRNA and 5S rRNA precursors are at least transiently associated with the La protein. This raises the possibility that the La protein may be an RNA polymerase III transcription factor.

VL - 12 ER - TY - JOUR T1 - Sequence of U1 RNA from Drosophila melanogaster: implications for U1 secondary structure and possible involvement in splicing. JF - Nucleic Acids Res Y1 - 1981 A1 - Mount, S M A1 - Steitz, J A KW - Animals KW - Antibodies KW - Autoimmune Diseases KW - Base Sequence KW - Cells, Cultured KW - Cloning, Molecular KW - Drosophila melanogaster KW - HUMANS KW - Lupus Erythematosus, Systemic KW - Nucleic Acid Conformation KW - Nucleic Acid Hybridization KW - Ribonuclease T1 KW - Ribonucleoproteins KW - RNA KW - RNA, Small Nuclear AB -

U1 RNA from cultured Drosophila melanogaster cells (Kc) was identified by its ability to be recognized, as an RNP, by anti-(U1)RNP antibodies from human lupus patients. Its sequence was deduced largely from direct analysis of the RNA molecule and then confirmed by DNA sequence determinations on a genomic clone isolated by hybridization to Drosophila U1 RNA. The Drosophila U1 RNA sequence exhibits 72% agreement with human U1 RNA. Nucleotides 3-11, which are complementary to the entire consensus sequence for donor (5') splice junctions in hnRNA, and to part of the acceptor (3') consensus, are exactly conserved. However, nucleotides 14-21, postulated to interact only with acceptor junctions, differ. Comparison of the Drosophila U1 sequence with vertebrate U1 sequences allows a particular secondary structure model to be preferred over others. These results are consistent with the hypothesis that U1 snRNPs are involved in splicing, but suggest specific modifications of the model detailing molecular interactions between U1 RNA and hnRNA during the splicing reaction.

VL - 9 CP - 23 ER - TY - JOUR T1 - Transcription of cloned tRNA and 5S RNA genes in a Drosophila cell free extract. JF - Nucleic Acids Res Y1 - 1981 A1 - Dingermann, T A1 - Sharp, S A1 - Appel, B A1 - DeFranco, D A1 - Mount, S A1 - Heiermann, R A1 - Pongs, O A1 - Söll, D KW - Animals KW - Cell-Free System KW - Cloning, Molecular KW - Drosophila KW - In Vitro Techniques KW - RNA KW - RNA Polymerase III KW - RNA, Transfer KW - Transcription, Genetic KW - Xenopus laevis AB -

We describe the preparation of a cell-free extract from Drosophila Kc cells which allows transcription of a variety of cloned eukaryotic RNA polymerase III genes. The extract has low RNA-processing nuclease activity and thus the major products obtained are primary transcripts.

VL - 9 CP - 16 ER - TY - JOUR T1 - Are snRNPs involved in splicing? JF - Nature Y1 - 1980 A1 - Lerner, M R A1 - Boyle, J A A1 - Mount, S M A1 - Wolin, S L A1 - Steitz, J A KW - Animals KW - Base Sequence KW - Cell Line KW - Chickens KW - Erythrocytes KW - HUMANS KW - Liver KW - Lupus Erythematosus, Systemic KW - Molecular Weight KW - Nucleic Acid Precursors KW - Nucleoproteins KW - Ribonucleoproteins KW - RNA, Heterogeneous Nuclear KW - Species Specificity VL - 283 CP - 5743 ER - TY - JOUR T1 - Detection of alloantigens during preimplantation development and early trophoblast differentiation in the mouse by immunoperoxidase labeling. JF - J Exp Med Y1 - 1976 A1 - Searle, R F A1 - Sellens, M H A1 - Elson, J A1 - Jenkinson, E J A1 - Billington, W D KW - Animals KW - Binding Sites, Antibody KW - Blastocyst KW - Cell Differentiation KW - Cell Membrane KW - Embryo Implantation KW - Embryonic Development KW - Epitopes KW - Female KW - Histocompatibility Antigens KW - HLA Antigens KW - Horseradish Peroxidase KW - Mice KW - Mice, Inbred Strains KW - Pregnancy KW - Pregnancy, Animal KW - Trophoblasts AB -

An immunoperoxidase-labeling technique allowing visualization of antibody binding to the cell surface at the electron microscopical level has been employed an an analysis of H-2 and non-H-2 alloantigen expression on the early mouse embryo. The presence of non-H-2 antigenic determinants has been confirmed on eight-cell, morula, and blastocyst stages of development. Contrary to previous reports, however, low levels of H-2 antigen have also been detected on the blastocyst. This is the earliest stage at which H-2 has been shown to be expressed on the fertilized mouse egg and may reflect the greater resolution of the immunoperoxidase technique. Using two different models to study the critical peri-implantation stages, those of experimentally induced blastocyst activation and blastocyst outgrowth in vitro, it has been demonstrated that antigen loss occurs on the trophectoderm at the time of implantation, and that this is not necessarily dependent upon maternal influence. It is suggested that the loss may be an important factor in the prevention of maternal immune rejection during the establishment of the fetal allograft. The two major components of the early postimplantation conceptus display a striking differential in antigenic status. The embryonic sac shows a high degree of peroxidase labeling, while the ectoplacental cone trophoblast is unlabeled. These findings add support to the concept of antigenic neutrality of the early trophoblast and its role in the maintenance of a normal fetomaternal immunological equilibrium.

VL - 143 CP - 2 ER - TY - JOUR T1 - Surgery of the hip and knee in patients with rheumatoid arthritis. JF - J Bone Joint Surg Am Y1 - 1973 A1 - Conaty, J P KW - Acetabulum KW - Arthritis, Rheumatoid KW - Arthrodesis KW - Arthroplasty KW - Contracture KW - Debridement KW - Femur Head KW - Femur Head Necrosis KW - Hip KW - Hip Joint KW - HUMANS KW - Joint Prosthesis KW - Knee KW - Knee Joint KW - Osteotomy KW - Patella KW - Postoperative Complications KW - Recurrence KW - Synovial Membrane KW - Tibia VL - 55 CP - 2 ER -