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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 - 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 -