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

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

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

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

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

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

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

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

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

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

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

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

VL - 10 CP - 5 M3 - 10.1371/journal.pone.0126729 ER - TY - Generic T1 - Evolutionary Conservation of Bacterial Essential Metabolic Genes across All Bacterial Culture Media Y1 - 2015 A1 - Ish-Am, Oren A1 - Kristensen, David M. A1 - Ruppin, Eytan ED - Thangaraj, Kumarasamy JA - PLOS ONE VL - 10 UR - http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0123785 CP - 4 J1 - PLoS ONE M3 - 10.1371/journal.pone.0123785 ER - TY - Generic T1 - Epiviz: interactive visual analytics for functional genomics data. Y1 - 2014 A1 - Chelaru, Florin A1 - Smith, Llewellyn A1 - Goldstein, Naomi A1 - Bravo, Héctor Corrada KW - algorithms KW - Chromosome mapping KW - Data Mining KW - database management systems KW - Databases, Genetic KW - Genomics KW - Internet KW - software KW - User-Computer Interface AB -

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

JA - Nat Methods VL - 11 CP - 9 M3 - 10.1038/nmeth.3038 ER - TY - Generic T1 - An evaluation of Monte-Carlo logic and logicFS motivated by a study of the regulation of gene expression in heart failure Y1 - 2014 A1 - Lu, Yun A1 - Hannenhalli, Sridhar A1 - Cappola, Tom A1 - Putt, Mary JA - Journal of Applied Statistics VL - 41 UR - http://www.tandfonline.com/doi/abs/10.1080/02664763.2014.898133 CP - 9 J1 - Journal of Applied Statistics M3 - 10.1080/02664763.2014.898133 ER - TY - JOUR T1 - Enhancer networks revealed by correlated DNAse hypersensitivity states of enhancers JF - Nucleic Acids ResNucleic Acids ResNucleic Acids Res Y1 - 2013 A1 - Malin, J. A1 - Aniba, M. R. A1 - Sridhar Hannenhalli KW - *Deoxyribonucleases KW - *Enhancer Elements, Genetic KW - Chromatin/chemistry KW - Gene expression KW - Gene Regulatory Networks KW - HUMANS KW - Transcription Factors/metabolism AB - Mammalian gene expression is often regulated by distal enhancers. However, little is known about higher order functional organization of enhancers. Using approximately 100 K P300-bound regions as candidate enhancers, we investigated their correlated activity across 72 cell types based on DNAse hypersensitivity. We found widespread correlated activity between enhancers, which decreases with increasing inter-enhancer genomic distance. We found that correlated enhancers tend to share common transcription factor (TF) binding motifs, and several chromatin modification enzymes preferentially interact with these TFs. Presence of shared motifs in enhancer pairs can predict correlated activity with 73% accuracy. Also, genes near correlated enhancers exhibit correlated expression and share common function. Correlated enhancers tend to be spatially proximal. Interestingly, weak enhancers tend to correlate with significantly greater numbers of other enhancers relative to strong enhancers. Furthermore, strong/weak enhancers preferentially correlate with strong/weak enhancers, respectively. We constructed enhancer networks based on shared motif and correlated activity and show significant functional enrichment in their putative target gene clusters. Overall, our analyses show extensive correlated activity among enhancers and reveal clusters of enhancers whose activities are coordinately regulated by multiple potential mechanisms involving shared TF binding, chromatin modifying enzymes and 3D chromatin structure, which ultimately co-regulate functionally linked genes. VL - 41 SN - 1362-4962 (Electronic)
0305-1048 (Linking) N1 - Malin, Justin
Aniba, Mohamed Radhouane
Hannenhalli, Sridhar
eng
R01 GM100335/GM/NIGMS NIH HHS/
R01GM100335/GM/NIGMS NIH HHS/
Research Support, N.I.H., Extramural
England
2013/05/24 06:00
Nucleic Acids Res. 2013 Aug;41(14):6828-38. doi: 10.1093/nar/gkt374. Epub 2013 May 21. U2 - 3737527 J1 - Nucleic acids researchNucleic acids research ER - TY - JOUR T1 - Exploring variation-aware contig graphs for (comparative) metagenomics using MaryGold JF - Bioinformatics (Oxford, England)Bioinformatics (Oxford, England) Y1 - 2013 A1 - Nijkamp, Jurgen F. A1 - M. Pop A1 - Reinders, Marcel J. T. A1 - de Ridder, Dick AB - MOTIVATION: Although many tools are available to study variation and its impact in single genomes, there is a lack of algorithms for finding such variation in metagenomes. This hampers the interpretation of metagenomics sequencing datasets, which are increasingly acquired in research on the (human) microbiome, in environmental studies and in the study of processes in the production of foods and beverages. Existing algorithms often depend on the use of reference genomes, which pose a problem when a metagenome of a priori unknown strain composition is studied. In this article, we develop a method to perform reference-free detection and visual exploration of genomic variation, both within a single metagenome and between metagenomes. RESULTS: We present the MaryGold algorithm and its implementation, which efficiently detects bubble structures in contig graphs using graph decomposition. These bubbles represent variable genomic regions in closely related strains in metagenomic samples. The variation found is presented in a condensed Circos-based visualization, which allows for easy exploration and interpretation of the found variation. We validated the algorithm on two simulated datasets containing three respectively seven Escherichia coli genomes and showed that finding allelic variation in these genomes improves assemblies. Additionally, we applied MaryGold to publicly available real metagenomic datasets, enabling us to find within-sample genomic variation in the metagenomes of a kimchi fermentation process, the microbiome of a premature infant and in microbial communities living on acid mine drainage. Moreover, we used MaryGold for between-sample variation detection and exploration by comparing sequencing data sampled at different time points for both of these datasets. AVAILABILITY: MaryGold has been written in C++ and Python and can be downloaded from http://bioinformatics.tudelft.nl/software VL - 29 N1 - http://www.ncbi.nlm.nih.gov/pubmed/24058058?dopt=Abstract ER - TY - JOUR T1 - Epigenomic model of cardiac enhancers with application to Genome wideassociation studies JF - Pacific Symposium on BiocomputingPacific Symposium on Biocomputing Y1 - 2012 A1 - Avinash, D. Sahu A1 - R. Aniba A1 - Y. C. Chang A1 - Sridhar Hannenhalli ER - TY - JOUR T1 - Exploiting sparseness in de novo genome assembly JF - BMC bioinformaticsBMC Bioinformatics Y1 - 2012 A1 - Chengxi Ye A1 - Ma, Z. S. A1 - Cannon, C. H. A1 - M. Pop A1 - Yu, D. W. PB - BioMed Central Ltd VL - 13 ER - TY - JOUR T1 - Effective detection of rare variants in pooled DNA samples using Cross-pool tailcurve analysis JF - Genome Biology Y1 - 2011 A1 - Niranjan, Tejasvi S A1 - Adamczyk, Abby A1 - Bravo, Hector A1 - Taub, Margaret A A1 - Wheelan, Sarah J A1 - Irizarry, Rafael A1 - Wang, Tao VL - 12 UR - http://genomebiology.biomedcentral.com/articles/10.1186/gb-2011-12-9-r93 CP - 9 J1 - Genome BiolGenome Biology M3 - 10.1186/gb-2011-12-9-r93 ER - TY - JOUR T1 - Epigenomic and RNA structural correlates of polyadenylation JF - RNA biologyRNA biology Y1 - 2011 A1 - Khaladkar, M. A1 - Smyda, M. A1 - Sridhar Hannenhalli PB - Landes Bioscience VL - 8 ER - TY - JOUR T1 - Extracting Between-Pathway Models from E-MAP Interactions Using Expected Graph Compression JF - Journal of Computational BiologyJournal of Computational Biology Y1 - 2011 A1 - Kelley, D. R. A1 - Kingsford, Carl VL - 18 ER - TY - JOUR T1 - Effect on Human Cells of Environmental Vibrio Parahaemolyticus Strains Carrying Type III Secretion System 2 JF - Infection and ImmunityInfect. Immun.Infection and ImmunityInfect. Immun. Y1 - 2010 A1 - Caburlotto, Greta A1 - Lleò, Maria M. A1 - Hilton, Tamara A1 - Huq, Anwar A1 - Rita R. Colwell A1 - Kaper, James B. AB - Vibrio parahaemolyticus is an inhabitant of estuarine and marine environments that causes seafood-borne gastroenteritis worldwide. Recently, a type 3 secretion system (T3SS2) able to secrete and translocate virulence factors into the eukaryotic cell has been identified in a pathogenicity island (VP-PAI) located on the smaller chromosome. These virulence-related genes have previously been detected only in clinical strains. Classical virulence genes for this species (tdh, trh) are rarely detected in environmental strains, which are usually considered to lack virulence potential. However, during screening of a collection of environmental V. parahaemolyticus isolates obtained in the North Adriatic Sea in Italy, a number of marine strains carrying virulence-related genes, including genes involved in the T3SS2, were detected. In this study, we investigated the pathogenic potential of these marine V. parahaemolyticus strains by studying their adherence ability, their cytotoxicity, their effect on zonula occludin protein 1 (ZO-1) of the tight junctions, and their effect on transepithelial resistance (TER) in infected Caco-2 cells. By performing a reverse transcription-PCR, we also tested the expression of the T3SS2 genes vopT and vopB2, encoding an effector and a translocon protein, respectively. Our results indicate that, similarly to clinical strains, marine V. parahaemolyticus strains carrying vopT and vopB2 and that other genes included in the VP-PAI are capable of adhering to human cells and of causing cytoskeletal disruption and loss of membrane integrity in infected cells. On the basis of data presented here, environmental V. parahaemolyticus strains should be included in coastal water surveillance plans, as they may represent a risk for human health. VL - 78 SN - 0019-9567, 1098-5522 ER - TY - JOUR T1 - Environmental reservoirs of Vibrio cholerae and their role in cholera JF - Environmental Microbiology ReportsEnvironmental Microbiology Reports Y1 - 2010 A1 - Vezzulli, Luigi A1 - Pruzzo, Carla A1 - Huq, Anwar A1 - Rita R. Colwell AB - In the aquatic environment, Vibrio cholerae has been reported to be associated with a variety of living organisms, including animals with an exoskeleton of chitin, aquatic plants, protozoa, bivalves, waterbirds, as well as abiotic substrates (e.g. sediments). Most of these are well-known or putative environmental reservoirs for the bacterium, defined as places where the pathogen lives over time, with the potential to be released and to cause human infection. Environmental reservoirs also serve as V. cholerae disseminators and vectors. They can be responsible for the start of an epidemic, may be critical to cholera endemicity, and affect the evolution of pathogen virulence. To date, in addition to the generally recognized role of zooplankton as the largest environmental reservoir for V. cholerae, other environmental reservoirs play some role in cholera epidemiology by favouring persistence of the pathogen during inter-epidemic periods. Little is known about the ecological factors affecting V. cholerae survival in association with aquatic substrates. Studies aimed at these aspects, i.e. understanding how environmental reservoirs interact, are affected by climate, and contribute to disease epidemiology, will be useful for understanding global implications of V. cholerae and the disease cholera. VL - 2 SN - 1758-2229 ER - TY - JOUR T1 - Evolutionary dynamics of U12-type spliceosomal introns. JF - BMC Evol Biol Y1 - 2010 A1 - Lin, Chiao-Feng A1 - Mount, Stephen M A1 - Jarmołowski, Artur A1 - Makałowski, Wojciech KW - Animals KW - Arabidopsis KW - Evolution, Molecular KW - HUMANS KW - Introns KW - RNA, Small Nuclear KW - Spliceosomes AB -

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

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

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

VL - 10 M3 - 10.1186/1471-2148-10-47 ER - TY - CHAP T1 - Evolutionary framework for Lepidoptera model systems T2 - Genetics and Molecular Biology of LepidopteraGenetics and Molecular Biology of Lepidoptera Y1 - 2010 A1 - Roe, A. A1 - Weller, S. A1 - Baixeras, J. A1 - Brown, J. W. A1 - Michael P. Cummings A1 - Davis, D. R. A1 - Horak, M. A1 - Kawahara, A. Y. A1 - Mitter, C. A1 - Parr, C. S. A1 - Regier, J. C. A1 - Rubinoff, D. A1 - Simonsen, T. J. A1 - Wahlberg, N. A1 - Zwick, A. ED - Goldsmith, M. ED - Marec, F. AB - “Model systems” are specific organisms upon which detailed studies have been conducted examining a fundamental biological question. If the studies are robust, their results can be extrapolated among an array of organisms that possess features in common with the subject organism. The true power of model systems lies in the ability to extrapolate these details across larger groups of organisms. In order to generalize these results, comparative studies are essential and require that model systems be placed into their evolutionary or phylogenetic context. This chapter examines model systems in the insect order Lepidoptera from the perspective of several different superfamilies. Historically, many species of Lepidoptera have been essential in the development of invaluable model systems in the fields of development biology, genetics, molecular biology, physiology, co-evolution, population dynamics, and ecology. JA - Genetics and Molecular Biology of LepidopteraGenetics and Molecular Biology of Lepidoptera PB - Taylor & Francis CY - Boca Raton ER - TY - Generic T1 - Exploring Biological Network Dynamics with Ensembles of Graph Partitions T2 - Proceedings of the PSB Pacific Symposium on Biocomputing Y1 - 2010 A1 - Navlakha, S. A1 - Kingsford, Carl JA - Proceedings of the PSB Pacific Symposium on Biocomputing VL - 15 ER - TY - JOUR T1 - Estimating Tree-Structured Covariance Matrices via Mixed-Integer Programming JF - J Mach Learn Res Y1 - 2009 A1 - Corrada Bravo, Hector A1 - Wright, Stephen A1 - Eng, Kevin H. A1 - Keles, Sündüz A1 - Wahba, Grace VL - 5 ER - TY - JOUR T1 - Evidence for Coregulation of Myocardial Gene Expression by MEF2 and NFAT in Human Heart FailureCLINICAL PERSPECTIVE JF - Circulation: Cardiovascular GeneticsCirculation: Cardiovascular Genetics Y1 - 2009 A1 - Putt, M. E. A1 - Sridhar Hannenhalli A1 - Lu, Y. A1 - Haines, P. A1 - Chandrupatla, H. R. A1 - Morrisey, E. E. A1 - Margulies, K. B. A1 - Cappola, T. P. PB - Am Heart Assoc VL - 2 ER - TY - JOUR T1 - The evolution of Fox genes and their role in development and disease JF - Nature reviews. GeneticsNat Rev GenetNature reviews. GeneticsNat Rev Genet Y1 - 2009 A1 - Sridhar Hannenhalli A1 - Kaestner, Klaus H. AB - The forkhead box (Fox) family of transcription factors, which originated in unicellular eukaryotes, has expanded over time through multiple duplication events, and sometimes through gene loss, to over 40 members in mammals. Fox genes have evolved to acquire a specialized function in many key biological processes. Mutations in Fox genes have a profound effect on human disease, causing phenotypes as varied as cancer, glaucoma and language disorders. We summarize the salient features of the evolution of the Fox gene family and highlight the diverse contribution of various Fox subfamilies to developmental processes, from organogenesis to speech acquisition. VL - 10 SN - 1471-0056 ER - TY - JOUR T1 - Examining the relative influence of familial, genetic, and environmental covariate information in flexible risk models JF - Proceedings of the National Academy of Sciences Y1 - 2009 A1 - Bravo, H. C. A1 - Lee, K. E. A1 - Klein, B. E. K. A1 - Klein, R. A1 - Iyengar, S. K. A1 - Wahba, G. VL - 106 UR - http://www.pnas.org/cgi/doi/10.1073/pnas.0902906106https://syndication.highwire.org/content/doi/10.1073/pnas.0902906106 CP - 20 J1 - Proceedings of the National Academy of Sciences M3 - 10.1073/pnas.0902906106 ER - TY - JOUR T1 - Extreme polymorphism in a vaccine antigen and risk of clinical malaria: implications for vaccine development JF - Sci Transl MedSci Transl Med Y1 - 2009 A1 - Takala, S. L. A1 - Coulibaly, D. A1 - Thera, M. A. A1 - Batchelor, A. H. A1 - Michael P. Cummings A1 - Escalante, A. A. A1 - Ouattara, A. A1 - Traoré, K. A1 - Niangaly, A. A1 - Djimdé, A. A. A1 - Doumbo, O. K. A1 - Plowe, C. V. AB - Vaccines directed against the blood stages of Plasmodium falciparum malaria are intended to prevent the parasite from invading and replicating within host cells. No blood-stage malaria vaccine has shown clinical efficacy in humans. Most malaria vaccine antigens are parasite surface proteins that have evolved extensive genetic diversity, and this diversity could allow malaria parasites to escape vaccine-induced immunity. We examined the extent and within-host dynamics of genetic diversity in the blood-stage malaria vaccine antigen apical membrane antigen-1 in a longitudinal study in Mali. Two hundred and fourteen unique apical membrane antigen-1 haplotypes were identified among 506 human infections, and amino acid changes near a putative invasion machinery binding site were strongly associated with the development of clinical symptoms, suggesting that these residues may be important to consider in designing polyvalent apical membrane antigen-1 vaccines and in assessing vaccine efficacy in field trials. This extreme diversity may pose a serious obstacle to an effective polyvalent recombinant subunit apical membrane antigen-1 vaccine. VL - 1 ER - TY - JOUR T1 - Environmental signatures associated with cholera epidemics JF - Proceedings of the National Academy of SciencesProceedings of the National Academy of Sciences Y1 - 2008 A1 - Constantin de Magny, G. A1 - Murtugudde, R. A1 - Sapiano, M. R. P. A1 - Nizam, A. A1 - Brown, C. W. A1 - Busalacchi, A. J. A1 - Yunus, M. A1 - Nair, G. B. A1 - Gil, A. I. A1 - Lanata, C. F. A1 - Rita R. Colwell AB - The causative agent of cholera, Vibrio cholerae, has been shown to be autochthonous to riverine, estuarine, and coastal waters along with its host, the copepod, a significant member of the zooplankton community. Temperature, salinity, rainfall and plankton have proven to be important factors in the ecology of V. cholerae, influencing the transmission of the disease in those regions of the world where the human population relies on untreated water as a source of drinking water. In this study, the pattern of cholera outbreaks during 1998–2006 in Kolkata, India, and Matlab, Bangladesh, and the earth observation data were analyzed with the objective of developing a prediction model for cholera. Satellite sensors were used to measure chlorophyll a concentration (CHL) and sea surface temperature (SST). In addition, rainfall data were obtained from both satellite and in situ gauge measurements. From the analyses, a statistically significant relationship between the time series for cholera in Kolkata, India, and CHL and rainfall anomalies was determined. A statistically significant one month lag was observed between CHL anomaly and number of cholera cases in Matlab, Bangladesh. From the results of the study, it is concluded that ocean and climate patterns are useful predictors of cholera epidemics, with the dynamics of endemic cholera being related to climate and/or changes in the aquatic ecosystem. When the ecology of V. cholerae is considered in predictive models, a robust early warning system for cholera in endemic regions of the world can be developed for public health planning and decision making.ecology epidemiology microbiology remote sensing VL - 105 SN - 0027-8424, 1091-6490 ER - TY - JOUR T1 - Environmental Vibrio spp., isolated in Mozambique, contain a polymorphic group of integrative conjugative elements and class 1 integrons JF - FEMS Microbiology EcologyFEMS Microbiology Ecology Y1 - 2008 A1 - Taviani, Elisa A1 - Ceccarelli, Daniela A1 - Lazaro, Nivalda A1 - Bani, Stefania A1 - Cappuccinelli, Piero A1 - Rita R. Colwell A1 - Colombo, Mauro M. KW - ICE KW - integron KW - Mozambique KW - Vibrio AB - Circulation of mobile genetic elements linked to drug resistance spread was studied in Vibrio strains isolated from surface urban water (river and sea) and shellfish samples in 2002–2003 in Maputo, Mozambique. Class 1 integrons and integrating conjugative elements (ICE) were investigated by PCR and mating experiments in strains of major health interest: 10 Vibrio cholerae, six Vibrio parahaemolyticus, two Vibrio alginolyticus and one Vibrio fluvialis. Resistance to at least two antibiotics (predominantly β-lactams) was detected in all the strains, with additional resistances to sulfamethoxazole, spectinomycin, streptomycin and/or trimethoprim. Class 1 integrons contributed partially to the expression of drug resistance and were found in five isolates: four V. cholerae (blaP1 cassette, one strain also contained the dfrA15 cassette) and one V. alginolyticus (aadA2 cassette). ICEs, apparently devoid of resistance genes, were found in eight V. cholerae, three V. parahaemolyticus and one V. fluvialis isolates. A wide variability was observed by molecular characterization of ICEs. Five ICEs were included in the SXT/R391 family and seven ICEs were not classified. Our results indicate that the SXT/R391 family and related ICEs comprise a large class of polymorphic genetic elements widely circulating in environmental Vibrio strains in Africa, beside those evidently linked to drug resistance in clinical isolates. VL - 64 SN - 1574-6941 ER - TY - RPRT T1 - Estimating Tree-Structured Covariance Matrices via Mixed-Integer Programming with an Application to Phylogenetic Analysis of Gene Expression Y1 - 2008 A1 - Héctor Corrada Bravo A1 - Eng, K. H. A1 - Keles, S. A1 - Wahba, G. A1 - Wright, S. AB - We present a novel method for estimating tree-structured covariance matrices directly fromobserved continuous data. A representation of these classes of matrices as linear combinations of rank-one matrices indicating object partitions is used to formulate estimation as instances of well-studied numerical optimization problems. In particular, we present estimation based on projection where the covariance estimate is the nearest tree-structured covariance matrix to an observed sample covariance matrix. The problem is posed as a linear or quadratic mixed-integer program (MIP) where a setting of the integer variables in the MIP specifies a set of tree topologies of the structured covariance matrix. We solve these problems to optimality using efficient and robust existing MIP solvers. We also show that the least squares distance method of Fitch and Margoliash (1967) can be formulated as a quadratic MIP and thus solved exactly using existing, robust branch-and-bound MIP solvers. Our motivation for this method is the discovery of phylogenetic structure directly from gene expression data. Recent studies have adapted traditional phylogenetic comparative anal- ysis methods to expression data. Typically, these methods first estimate a phylogenetic tree from genomic sequence data and subsequently analyze expression data. A covariance matrix constructed from the sequence-derived tree is used to correct for the lack of independence in phy- logenetically related taxa. However, recent results have shown that the hierarchical structure of sequence-derived tree estimates are highly sensitive to the genomic region chosen to build them. To circumvent this difficulty, we propose a stable method for deriving tree-structured covariance matrices directly from gene expression as an exploratory step that can guide investigators in their modelling choices for these types of comparative analysis. We present a case study in phylogenetic analysis of expression in yeast gene families. Our method is able to corroborate the presence of phylogenetic structure in the response of expression in a subset of the gene families under particular experimental conditions. Additionally, when used in conjunction with transcription factor occupancy data, our methods show that alternative modelling choices should be considered when creating sequence-derived trees for this comparative analysis. PB - Department of Statistics, University of Wisconsin VL - 1142 ER - TY - JOUR T1 - Eukaryotic Transcription Factor Binding Sites—modeling and Integrative Search Methods JF - BioinformaticsBioinformaticsBioinformaticsBioinformatics Y1 - 2008 A1 - Sridhar Hannenhalli AB - A comprehensive knowledge of transcription factor binding sites (TFBS) is important for a mechanistic understanding of transcriptional regulation as well as for inferring gene regulatory networks. Because the DNA motif recognized by a transcription factor is typically short and degenerate, computational approaches for identifying binding sites based only on the sequence motif inevitably suffer from high error rates. Current state-of-the-art techniques for improving computational identification of binding sites can be broadly categorized into two classes: (1) approaches that aim to improve binding motif models by extracting maximal sequence information from experimentally determined binding sites and (2) approaches that supplement binding motif models with additional genomic or other attributes (such as evolutionary conservation). In this review we will discuss recent attempts to improve computational identification of TFBS through these two types of approaches and conclude with thoughts on future development.Contact: sridharh@pcbi.upenn.edu VL - 24 SN - 1367-4803, 1460-2059 ER - TY - CHAP T1 - Expanding the reach of Grid computing: combining Globus- and BOINC-based systems T2 - Grids for Bioinformatics and Computational BiologyGrids for Bioinformatics and Computational Biology Y1 - 2008 A1 - Myers, D. S. A1 - Adam L. Bazinet A1 - Michael P. Cummings ED - Talbi, E. G. ED - Zomaya, A. Y. JA - Grids for Bioinformatics and Computational BiologyGrids for Bioinformatics and Computational Biology T3 - Wiley Book Series on Bioinformatics: Computational Techniques and Engineering PB - Wiley-Interscience CY - Hoboken ER - TY - JOUR T1 - Eukaryotic Transcriptional Regulation: Signals, Interactions, and Modules JF - Computational Genomics: Current MethodsComputational Genomics: Current Methods Y1 - 2007 A1 - Sridhar Hannenhalli PB - Taylor & Francis ER - TY - JOUR T1 - Evolution of genes and genomes on the Drosophila phylogeny JF - NatureNature Y1 - 2007 A1 - Clark, Andrew G. A1 - Eisen, Michael B. A1 - Smith, Douglas R. A1 - Bergman, Casey M. A1 - Oliver, Brian A1 - Markow, Therese A. A1 - Kaufman, Thomas C. A1 - Kellis, Manolis A1 - Gelbart, William A1 - Iyer, Venky N. A1 - Pollard, Daniel A. A1 - Sackton, Timothy B. A1 - Larracuente, Amanda M. A1 - Singh, Nadia D. A1 - Abad, Jose P. A1 - Abt, Dawn N. A1 - Adryan, Boris A1 - Aguade, Montserrat A1 - Akashi, Hiroshi A1 - Anderson, Wyatt W. A1 - Aquadro, Charles F. A1 - Ardell, David H. A1 - Arguello, Roman A1 - Artieri, Carlo G. A1 - Barbash, Daniel A. A1 - Barker, Daniel A1 - Barsanti, Paolo A1 - Batterham, Phil A1 - Batzoglou, Serafim A1 - Begun, Dave A1 - Bhutkar, Arjun A1 - Blanco, Enrico A1 - Bosak, Stephanie A. A1 - Bradley, Robert K. A1 - Brand, Adrianne D. A1 - Brent, Michael R. A1 - Brooks, Angela N. A1 - Brown, Randall H. A1 - Butlin, Roger K. A1 - Caggese, Corrado A1 - Calvi, Brian R. A1 - Carvalho, A. Bernardo de A1 - Caspi, Anat A1 - Castrezana, Sergio A1 - Celniker, Susan E. A1 - Chang, Jean L. A1 - Chapple, Charles A1 - Chatterji, Sourav A1 - Chinwalla, Asif A1 - Civetta, Alberto A1 - Clifton, Sandra W. A1 - Comeron, Josep M. A1 - Costello, James C. A1 - Coyne, Jerry A. A1 - Daub, Jennifer A1 - David, Robert G. A1 - Delcher, Arthur L. A1 - Delehaunty, Kim A1 - Do, Chuong B. A1 - Ebling, Heather A1 - Edwards, Kevin A1 - Eickbush, Thomas A1 - Evans, Jay D. A1 - Filipski, Alan A1 - Findei, A1 - Sven A1 - Freyhult, Eva A1 - Fulton, Lucinda A1 - Fulton, Robert A1 - Garcia, Ana C. L. A1 - Gardiner, Anastasia A1 - Garfield, David A. A1 - Garvin, Barry E. A1 - Gibson, Greg A1 - Gilbert, Don A1 - Gnerre, Sante A1 - Godfrey, Jennifer A1 - Good, Robert A1 - Gotea, Valer A1 - Gravely, Brenton A1 - Greenberg, Anthony J. A1 - Griffiths-Jones, Sam A1 - Gross, Samuel A1 - Guigo, Roderic A1 - Gustafson, Erik A. A1 - Haerty, Wilfried A1 - Hahn, Matthew W. A1 - Halligan, Daniel L. A1 - Halpern, Aaron L. A1 - Halter, Gillian M. A1 - Han, Mira V. A1 - Heger, Andreas A1 - Hillier, LaDeana A1 - Hinrichs, Angie S. A1 - Holmes, Ian A1 - Hoskins, Roger A. A1 - Hubisz, Melissa J. A1 - Hultmark, Dan A1 - Huntley, Melanie A. A1 - Jaffe, David B. A1 - Jagadeeshan, Santosh A1 - Jeck, William R. A1 - Johnson, Justin A1 - Jones, Corbin D. A1 - Jordan, William C. A1 - Karpen, Gary H. A1 - Kataoka, Eiko A1 - Keightley, Peter D. A1 - Kheradpour, Pouya A1 - Kirkness, Ewen F. A1 - Koerich, Leonardo B. A1 - Kristiansen, Karsten A1 - Kudrna, Dave A1 - Kulathinal, Rob J. A1 - Kumar, Sudhir A1 - Kwok, Roberta A1 - Lander, Eric A1 - Langley, Charles H. A1 - Lapoint, Richard A1 - Lazzaro, Brian P. A1 - Lee, So-Jeong A1 - Levesque, Lisa A1 - Li, Ruiqiang A1 - Lin, Chiao-Feng A1 - Lin, Michael F. A1 - Lindblad-Toh, Kerstin A1 - Llopart, Ana A1 - Long, Manyuan A1 - Low, Lloyd A1 - Lozovsky, Elena A1 - Lu, Jian A1 - Luo, Meizhong A1 - Machado, Carlos A. A1 - Makalowski, Wojciech A1 - Marzo, Mar A1 - Matsuda, Muneo A1 - Matzkin, Luciano A1 - McAllister, Bryant A1 - McBride, Carolyn S. A1 - McKernan, Brendan A1 - McKernan, Kevin A1 - Mendez-Lago, Maria A1 - Minx, Patrick A1 - Mollenhauer, Michael U. A1 - Montooth, Kristi A1 - Stephen M. Mount A1 - Mu, Xu A1 - Myers, Eugene A1 - Negre, Barbara A1 - Newfeld, Stuart A1 - Nielsen, Rasmus A1 - Noor, Mohamed A. F. A1 - O'Grady, Patrick A1 - Pachter, Lior A1 - Papaceit, Montserrat A1 - Parisi, Matthew J. A1 - Parisi, Michael A1 - Parts, Leopold A1 - Pedersen, Jakob S. A1 - Pesole, Graziano A1 - Phillippy, Adam M. A1 - Ponting, Chris P. A1 - M. Pop A1 - Porcelli, Damiano A1 - Powell, Jeffrey R. A1 - Prohaska, Sonja A1 - Pruitt, Kim A1 - Puig, Marta A1 - Quesneville, Hadi A1 - Ram, Kristipati Ravi A1 - Rand, David A1 - Rasmussen, Matthew D. A1 - Reed, Laura K. A1 - Reenan, Robert A1 - Reily, Amy A1 - Remington, Karin A. A1 - Rieger, Tania T. A1 - Ritchie, Michael G. A1 - Robin, Charles A1 - Rogers, Yu-Hui A1 - Rohde, Claudia A1 - Rozas, Julio A1 - Rubenfield, Marc J. A1 - Ruiz, Alfredo A1 - Russo, Susan A1 - Salzberg, Steven L. A1 - Sanchez-Gracia, Alejandro A1 - Saranga, David J. A1 - Sato, Hajime A1 - Schaeffer, Stephen W. A1 - Schatz, Michael C. A1 - Schlenke, Todd A1 - Schwartz, Russell A1 - Segarra, Carmen A1 - Singh, Rama S. A1 - Sirot, Laura A1 - Sirota, Marina A1 - Sisneros, Nicholas B. A1 - Smith, Chris D. A1 - Smith, Temple F. A1 - Spieth, John A1 - Stage, Deborah E. A1 - Stark, Alexander A1 - Stephan, Wolfgang A1 - Strausberg, Robert L. A1 - Strempel, Sebastian A1 - Sturgill, David A1 - Sutton, Granger A1 - Sutton, Granger G. A1 - Tao, Wei A1 - Teichmann, Sarah A1 - Tobari, Yoshiko N. A1 - Tomimura, Yoshihiko A1 - Tsolas, Jason M. A1 - Valente, Vera L. S. A1 - Venter, Eli A1 - Venter, J. Craig A1 - Vicario, Saverio A1 - Vieira, Filipe G. A1 - Vilella, Albert J. A1 - Villasante, Alfredo A1 - Walenz, Brian A1 - Wang, Jun A1 - Wasserman, Marvin A1 - Watts, Thomas A1 - Wilson, Derek A1 - Wilson, Richard K. A1 - Wing, Rod A. A1 - Wolfner, Mariana F. A1 - Wong, Alex A1 - Wong, Gane Ka-Shu A1 - Wu, Chung- I. A1 - Wu, Gabriel A1 - Yamamoto, Daisuke A1 - Yang, Hsiao-Pei A1 - Yang, Shiaw-Pyng A1 - Yorke, James A. A1 - Yoshida, Kiyohito A1 - Zdobnov, Evgeny A1 - Zhang, Peili A1 - Zhang, Yu A1 - Zimin, Aleksey V. A1 - Baldwin, Jennifer A1 - Abdouelleil, Amr A1 - Abdulkadir, Jamal A1 - Abebe, Adal A1 - Abera, Brikti A1 - Abreu, Justin A1 - Acer, St Christophe A1 - Aftuck, Lynne A1 - Alexander, Allen A1 - An, Peter A1 - Anderson, Erica A1 - Anderson, Scott A1 - Arachi, Harindra A1 - Azer, Marc A1 - Bachantsang, Pasang A1 - Barry, Andrew A1 - Bayul, Tashi A1 - Berlin, Aaron A1 - Bessette, Daniel A1 - Bloom, Toby A1 - Blye, Jason A1 - Boguslavskiy, Leonid A1 - Bonnet, Claude A1 - Boukhgalter, Boris A1 - Bourzgui, Imane A1 - Brown, Adam A1 - Cahill, Patrick A1 - Channer, Sheridon A1 - Cheshatsang, Yama A1 - Chuda, Lisa A1 - Citroen, Mieke A1 - Collymore, Alville A1 - Cooke, Patrick A1 - Costello, Maura A1 - D'Aco, Katie A1 - Daza, Riza A1 - Haan, Georgius De A1 - DeGray, Stuart A1 - DeMaso, Christina A1 - Dhargay, Norbu A1 - Dooley, Kimberly A1 - Dooley, Erin A1 - Doricent, Missole A1 - Dorje, Passang A1 - Dorjee, Kunsang A1 - Dupes, Alan A1 - Elong, Richard A1 - Falk, Jill A1 - Farina, Abderrahim A1 - Faro, Susan A1 - Ferguson, Diallo A1 - Fisher, Sheila A1 - Foley, Chelsea D. A1 - Franke, Alicia A1 - Friedrich, Dennis A1 - Gadbois, Loryn A1 - Gearin, Gary A1 - Gearin, Christina R. A1 - Giannoukos, Georgia A1 - Goode, Tina A1 - Graham, Joseph A1 - Grandbois, Edward A1 - Grewal, Sharleen A1 - Gyaltsen, Kunsang A1 - Hafez, Nabil A1 - Hagos, Birhane A1 - Hall, Jennifer A1 - Henson, Charlotte A1 - Hollinger, Andrew A1 - Honan, Tracey A1 - Huard, Monika D. A1 - Hughes, Leanne A1 - Hurhula, Brian A1 - Husby, M. Erii A1 - Kamat, Asha A1 - Kanga, Ben A1 - Kashin, Seva A1 - Khazanovich, Dmitry A1 - Kisner, Peter A1 - Lance, Krista A1 - Lara, Marcia A1 - Lee, William A1 - Lennon, Niall A1 - Letendre, Frances A1 - LeVine, Rosie A1 - Lipovsky, Alex A1 - Liu, Xiaohong A1 - Liu, Jinlei A1 - Liu, Shangtao A1 - Lokyitsang, Tashi A1 - Lokyitsang, Yeshi A1 - Lubonja, Rakela A1 - Lui, Annie A1 - MacDonald, Pen A1 - Magnisalis, Vasilia A1 - Maru, Kebede A1 - Matthews, Charles A1 - McCusker, William A1 - McDonough, Susan A1 - Mehta, Teena A1 - Meldrim, James A1 - Meneus, Louis A1 - Mihai, Oana A1 - Mihalev, Atanas A1 - Mihova, Tanya A1 - Mittelman, Rachel A1 - Mlenga, Valentine A1 - Montmayeur, Anna A1 - Mulrain, Leonidas A1 - Navidi, Adam A1 - Naylor, Jerome A1 - Negash, Tamrat A1 - Nguyen, Thu A1 - Nguyen, Nga A1 - Nicol, Robert A1 - Norbu, Choe A1 - Norbu, Nyima A1 - Novod, Nathaniel A1 - O'Neill, Barry A1 - Osman, Sahal A1 - Markiewicz, Eva A1 - Oyono, Otero L. A1 - Patti, Christopher A1 - Phunkhang, Pema A1 - Pierre, Fritz A1 - Priest, Margaret A1 - Raghuraman, Sujaa A1 - Rege, Filip A1 - Reyes, Rebecca A1 - Rise, Cecil A1 - Rogov, Peter A1 - Ross, Keenan A1 - Ryan, Elizabeth A1 - Settipalli, Sampath A1 - Shea, Terry A1 - Sherpa, Ngawang A1 - Shi, Lu A1 - Shih, Diana A1 - Sparrow, Todd A1 - Spaulding, Jessica A1 - Stalker, John A1 - Stange-Thomann, Nicole A1 - Stavropoulos, Sharon A1 - Stone, Catherine A1 - Strader, Christopher A1 - Tesfaye, Senait A1 - Thomson, Talene A1 - Thoulutsang, Yama A1 - Thoulutsang, Dawa A1 - Topham, Kerri A1 - Topping, Ira A1 - Tsamla, Tsamla A1 - Vassiliev, Helen A1 - Vo, Andy A1 - Wangchuk, Tsering A1 - Wangdi, Tsering A1 - Weiand, Michael A1 - Wilkinson, Jane A1 - Wilson, Adam A1 - Yadav, Shailendra A1 - Young, Geneva A1 - Yu, Qing A1 - Zembek, Lisa A1 - Zhong, Danni A1 - Zimmer, Andrew A1 - Zwirko, Zac A1 - Jaffe, David B. A1 - Alvarez, Pablo A1 - Brockman, Will A1 - Butler, Jonathan A1 - Chin, CheeWhye A1 - Gnerre, Sante A1 - Grabherr, Manfred A1 - Kleber, Michael A1 - Mauceli, Evan A1 - MacCallum, Iain AB - Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species. VL - 450 SN - 0028-0836 N1 - [szlig] ER - TY - JOUR T1 - Evolution of genes and genomes on the Drosophila phylogeny. JF - Nature Y1 - 2007 A1 - Clark, Andrew G A1 - Eisen, Michael B A1 - Smith, Douglas R A1 - Bergman, Casey M A1 - Oliver, Brian A1 - Markow, Therese A A1 - Kaufman, Thomas C A1 - Kellis, Manolis A1 - Gelbart, William A1 - Iyer, Venky N A1 - Pollard, Daniel A A1 - Sackton, Timothy B A1 - Larracuente, Amanda M A1 - Singh, Nadia D A1 - Abad, Jose P A1 - Abt, Dawn N A1 - Adryan, Boris A1 - Aguade, Montserrat A1 - Akashi, Hiroshi A1 - Anderson, Wyatt W A1 - Aquadro, Charles F A1 - Ardell, David H A1 - Arguello, Roman A1 - Artieri, Carlo G A1 - Barbash, Daniel A A1 - Barker, Daniel A1 - Barsanti, Paolo A1 - Batterham, Phil A1 - Batzoglou, Serafim A1 - Begun, Dave A1 - Bhutkar, Arjun A1 - Blanco, Enrico A1 - Bosak, Stephanie A A1 - Bradley, Robert K A1 - Brand, Adrianne D A1 - Brent, Michael R A1 - Brooks, Angela N A1 - Brown, Randall H A1 - Butlin, Roger K A1 - Caggese, Corrado A1 - Calvi, Brian R A1 - Bernardo de Carvalho, A A1 - Caspi, Anat A1 - Castrezana, Sergio A1 - Celniker, Susan E A1 - Chang, Jean L A1 - Chapple, Charles A1 - Chatterji, Sourav A1 - Chinwalla, Asif A1 - Civetta, Alberto A1 - Clifton, Sandra W A1 - Comeron, Josep M A1 - Costello, James C A1 - Coyne, Jerry A A1 - Daub, Jennifer A1 - David, Robert G A1 - Delcher, Arthur L A1 - Delehaunty, Kim A1 - Do, Chuong B A1 - Ebling, Heather A1 - Edwards, Kevin A1 - Eickbush, Thomas A1 - Evans, Jay D A1 - Filipski, Alan A1 - Findeiss, Sven A1 - Freyhult, Eva A1 - Fulton, Lucinda A1 - Fulton, Robert A1 - Garcia, Ana C L A1 - Gardiner, Anastasia A1 - Garfield, David A A1 - Garvin, Barry E A1 - Gibson, Greg A1 - Gilbert, Don A1 - Gnerre, Sante A1 - Godfrey, Jennifer A1 - Good, Robert A1 - Gotea, Valer A1 - Gravely, Brenton A1 - Greenberg, Anthony J A1 - Griffiths-Jones, Sam A1 - Gross, Samuel A1 - Guigo, Roderic A1 - Gustafson, Erik A A1 - Haerty, Wilfried A1 - Hahn, Matthew W A1 - Halligan, Daniel L A1 - Halpern, Aaron L A1 - Halter, Gillian M A1 - Han, Mira V A1 - Heger, Andreas A1 - Hillier, LaDeana A1 - Hinrichs, Angie S A1 - Holmes, Ian A1 - Hoskins, Roger A A1 - Hubisz, Melissa J A1 - Hultmark, Dan A1 - Huntley, Melanie A A1 - Jaffe, David B A1 - Jagadeeshan, Santosh A1 - Jeck, William R A1 - Johnson, Justin A1 - Jones, Corbin D A1 - Jordan, William C A1 - Karpen, Gary H A1 - Kataoka, Eiko A1 - Keightley, Peter D A1 - Kheradpour, Pouya A1 - Kirkness, Ewen F A1 - Koerich, Leonardo B A1 - Kristiansen, Karsten A1 - Kudrna, Dave A1 - Kulathinal, Rob J A1 - Kumar, Sudhir A1 - Kwok, Roberta A1 - Lander, Eric A1 - Langley, Charles H A1 - Lapoint, Richard A1 - Lazzaro, Brian P A1 - Lee, So-Jeong A1 - Levesque, Lisa A1 - Li, Ruiqiang A1 - Lin, Chiao-Feng A1 - Lin, Michael F A1 - Lindblad-Toh, Kerstin A1 - Llopart, Ana A1 - Long, Manyuan A1 - Low, Lloyd A1 - Lozovsky, Elena A1 - Lu, Jian A1 - Luo, Meizhong A1 - Machado, Carlos A A1 - Makalowski, Wojciech A1 - Marzo, Mar A1 - Matsuda, Muneo A1 - Matzkin, Luciano A1 - McAllister, Bryant A1 - McBride, Carolyn S A1 - McKernan, Brendan A1 - McKernan, Kevin A1 - Mendez-Lago, Maria A1 - Minx, Patrick A1 - Mollenhauer, Michael U A1 - Montooth, Kristi A1 - Mount, Stephen M A1 - Mu, Xu A1 - Myers, Eugene A1 - Negre, Barbara A1 - Newfeld, Stuart A1 - Nielsen, Rasmus A1 - Noor, Mohamed A F A1 - O'Grady, Patrick A1 - Pachter, Lior A1 - Papaceit, Montserrat A1 - Parisi, Matthew J A1 - Parisi, Michael A1 - Parts, Leopold A1 - Pedersen, Jakob S A1 - Pesole, Graziano A1 - Phillippy, Adam M A1 - Ponting, Chris P A1 - Pop, Mihai A1 - Porcelli, Damiano A1 - Powell, Jeffrey R A1 - Prohaska, Sonja A1 - Pruitt, Kim A1 - Puig, Marta A1 - Quesneville, Hadi A1 - Ram, Kristipati Ravi A1 - Rand, David A1 - Rasmussen, Matthew D A1 - Reed, Laura K A1 - Reenan, Robert A1 - Reily, Amy A1 - Remington, Karin A A1 - Rieger, Tania T A1 - Ritchie, Michael G A1 - Robin, Charles A1 - Rogers, Yu-Hui A1 - Rohde, Claudia A1 - Rozas, Julio A1 - Rubenfield, Marc J A1 - Ruiz, Alfredo A1 - Russo, Susan A1 - Salzberg, Steven L A1 - Sanchez-Gracia, Alejandro A1 - Saranga, David J A1 - Sato, Hajime A1 - Schaeffer, Stephen W A1 - Schatz, Michael C A1 - Schlenke, Todd A1 - Schwartz, Russell A1 - Segarra, Carmen A1 - Singh, Rama S A1 - Sirot, Laura A1 - Sirota, Marina A1 - Sisneros, Nicholas B A1 - Smith, Chris D A1 - Smith, Temple F A1 - Spieth, John A1 - Stage, Deborah E A1 - Stark, Alexander A1 - Stephan, Wolfgang A1 - Strausberg, Robert L A1 - Strempel, Sebastian A1 - Sturgill, David A1 - Sutton, Granger A1 - Sutton, Granger G A1 - Tao, Wei A1 - Teichmann, Sarah A1 - Tobari, Yoshiko N A1 - Tomimura, Yoshihiko A1 - Tsolas, Jason M A1 - Valente, Vera L S A1 - Venter, Eli A1 - Venter, J Craig A1 - Vicario, Saverio A1 - Vieira, Filipe G A1 - Vilella, Albert J A1 - Villasante, Alfredo A1 - Walenz, Brian A1 - Wang, Jun A1 - Wasserman, Marvin A1 - Watts, Thomas A1 - Wilson, Derek A1 - Wilson, Richard K A1 - Wing, Rod A A1 - Wolfner, Mariana F A1 - Wong, Alex A1 - Wong, Gane Ka-Shu A1 - Wu, Chung-I A1 - Wu, Gabriel A1 - Yamamoto, Daisuke A1 - Yang, Hsiao-Pei A1 - Yang, Shiaw-Pyng A1 - Yorke, James A A1 - Yoshida, Kiyohito A1 - Zdobnov, Evgeny A1 - Zhang, Peili A1 - Zhang, Yu A1 - Zimin, Aleksey V A1 - Baldwin, Jennifer A1 - Abdouelleil, Amr A1 - Abdulkadir, Jamal A1 - Abebe, Adal A1 - Abera, Brikti A1 - Abreu, Justin A1 - Acer, St Christophe A1 - Aftuck, Lynne A1 - Alexander, Allen A1 - An, Peter A1 - Anderson, Erica A1 - Anderson, Scott A1 - Arachi, Harindra A1 - Azer, Marc A1 - Bachantsang, Pasang A1 - Barry, Andrew A1 - Bayul, Tashi A1 - Berlin, Aaron A1 - Bessette, Daniel A1 - Bloom, Toby A1 - Blye, Jason A1 - Boguslavskiy, Leonid A1 - Bonnet, Claude A1 - Boukhgalter, Boris A1 - Bourzgui, Imane A1 - Brown, Adam A1 - Cahill, Patrick A1 - Channer, Sheridon A1 - Cheshatsang, Yama A1 - Chuda, Lisa A1 - Citroen, Mieke A1 - Collymore, Alville A1 - Cooke, Patrick A1 - Costello, Maura A1 - D'Aco, Katie A1 - Daza, Riza A1 - De Haan, Georgius A1 - DeGray, Stuart A1 - DeMaso, Christina A1 - Dhargay, Norbu A1 - Dooley, Kimberly A1 - Dooley, Erin A1 - Doricent, Missole A1 - Dorje, Passang A1 - Dorjee, Kunsang A1 - Dupes, Alan A1 - Elong, Richard A1 - Falk, Jill A1 - Farina, Abderrahim A1 - Faro, Susan A1 - Ferguson, Diallo A1 - Fisher, Sheila A1 - Foley, Chelsea D A1 - Franke, Alicia A1 - Friedrich, Dennis A1 - Gadbois, Loryn A1 - Gearin, Gary A1 - Gearin, Christina R A1 - Giannoukos, Georgia A1 - Goode, Tina A1 - Graham, Joseph A1 - Grandbois, Edward A1 - Grewal, Sharleen A1 - Gyaltsen, Kunsang A1 - Hafez, Nabil A1 - Hagos, Birhane A1 - Hall, Jennifer A1 - Henson, Charlotte A1 - Hollinger, Andrew A1 - Honan, Tracey A1 - Huard, Monika D A1 - Hughes, Leanne A1 - Hurhula, Brian A1 - Husby, M Erii A1 - Kamat, Asha A1 - Kanga, Ben A1 - Kashin, Seva A1 - Khazanovich, Dmitry A1 - Kisner, Peter A1 - Lance, Krista A1 - Lara, Marcia A1 - Lee, William A1 - Lennon, Niall A1 - Letendre, Frances A1 - LeVine, Rosie A1 - Lipovsky, Alex A1 - Liu, Xiaohong A1 - Liu, Jinlei A1 - Liu, Shangtao A1 - Lokyitsang, Tashi A1 - Lokyitsang, Yeshi A1 - Lubonja, Rakela A1 - Lui, Annie A1 - MacDonald, Pen A1 - Magnisalis, Vasilia A1 - Maru, Kebede A1 - Matthews, Charles A1 - McCusker, William A1 - McDonough, Susan A1 - Mehta, Teena A1 - Meldrim, James A1 - Meneus, Louis A1 - Mihai, Oana A1 - Mihalev, Atanas A1 - Mihova, Tanya A1 - Mittelman, Rachel A1 - Mlenga, Valentine A1 - Montmayeur, Anna A1 - Mulrain, Leonidas A1 - Navidi, Adam A1 - Naylor, Jerome A1 - Negash, Tamrat A1 - Nguyen, Thu A1 - Nguyen, Nga A1 - Nicol, Robert A1 - Norbu, Choe A1 - Norbu, Nyima A1 - Novod, Nathaniel A1 - O'Neill, Barry A1 - Osman, Sahal A1 - Markiewicz, Eva A1 - Oyono, Otero L A1 - Patti, Christopher A1 - Phunkhang, Pema A1 - Pierre, Fritz A1 - Priest, Margaret A1 - Raghuraman, Sujaa A1 - Rege, Filip A1 - Reyes, Rebecca A1 - Rise, Cecil A1 - Rogov, Peter A1 - Ross, Keenan A1 - Ryan, Elizabeth A1 - Settipalli, Sampath A1 - Shea, Terry A1 - Sherpa, Ngawang A1 - Shi, Lu A1 - Shih, Diana A1 - Sparrow, Todd A1 - Spaulding, Jessica A1 - Stalker, John A1 - Stange-Thomann, Nicole A1 - Stavropoulos, Sharon A1 - Stone, Catherine A1 - Strader, Christopher A1 - Tesfaye, Senait A1 - Thomson, Talene A1 - Thoulutsang, Yama A1 - Thoulutsang, Dawa A1 - Topham, Kerri A1 - Topping, Ira A1 - Tsamla, Tsamla A1 - Vassiliev, Helen A1 - Vo, Andy A1 - Wangchuk, Tsering A1 - Wangdi, Tsering A1 - Weiand, Michael A1 - Wilkinson, Jane A1 - Wilson, Adam A1 - Yadav, Shailendra A1 - Young, Geneva A1 - Yu, Qing A1 - Zembek, Lisa A1 - Zhong, Danni A1 - Zimmer, Andrew A1 - Zwirko, Zac A1 - Jaffe, David B A1 - Alvarez, Pablo A1 - Brockman, Will A1 - Butler, Jonathan A1 - Chin, CheeWhye A1 - Gnerre, Sante A1 - Grabherr, Manfred A1 - Kleber, Michael A1 - Mauceli, Evan A1 - MacCallum, Iain KW - Animals KW - Codon KW - DNA Transposable Elements KW - Drosophila KW - Drosophila Proteins KW - Evolution, Molecular KW - Gene Order KW - Genes, Insect KW - Genome, Insect KW - Genome, Mitochondrial KW - Genomics KW - Immunity KW - Multigene Family KW - Phylogeny KW - Reproduction KW - RNA, Untranslated KW - sequence alignment KW - Sequence Analysis, DNA KW - Synteny AB -

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

VL - 450 CP - 7167 M3 - 10.1038/nature06341 ER - TY - JOUR T1 - The Expression of a Plant-type Ferredoxin Redox System provides Molecular Evidence for a Plastid in the Early Dinoflagellate Perkinsus marinus JF - ProtistProtist Y1 - 2007 A1 - Stelter, Kathrin A1 - Najib M. El‐Sayed A1 - Seeber, Frank KW - Apicomplexa KW - ferredoxin KW - Perkinsozoa KW - plastid KW - transit peptide AB - Perkinsus marinus is a parasitic protozoan with a phylogenetic positioning between Apicomplexa and dinoflagellates. It is thus of interest for reconstructing the early evolution of eukaryotes, especially with regard to the acquisition of secondary plastids in these organisms. It is also an important pathogen of oysters, and the definition of parasite-specific metabolic pathways would be beneficial for the identification of efficient treatments for infected mollusks. Although these different scientific interests have resulted in the start of a genome project for this organism, it is still unknown whether P. marinus contains a plastid or plastid-like organelle like the related dinoflagellates and Apicomplexa. Here, we show that in vitro-cultivated parasites contain transcripts of the plant-type ferredoxin and its associated reductase. Both proteins are nuclear-encoded and possess N-terminal targeting sequences similar to those characterized in dinoflagellates. Since this redox pair is exclusively found in cyanobacteria and plastid-harboring organisms its presence also in P. marinus is highly indicative of a plastid. We also provide additional evidence for such an organelle by demonstrating pharmacological sensitivity to inhibitors of plastid-localized enzymes involved in fatty acid biosynthesis (e.g. acetyl-CoA carboxylase) and by detection of genes for three enzymes of plastid-localized isoprenoid biosynthesis (1-deoxy-D-xylulose 5-phosphate reductoisomerase, (E)-4-hydroxy-3-methyl-but-2-enyl diphosphate reductase, and (E)-4-hydroxy-3-methyl-but-2-enyl diphosphate synthase). VL - 158 SN - 1434-4610 ER - TY - JOUR T1 - Effect of transport at ambient temperature on detection and isolation of Vibrio cholerae from environmental samples JF - Applied and environmental microbiologyApplied and environmental microbiology Y1 - 2006 A1 - Alam, M. A1 - Sadique, A. A1 - Bhuiyan, N. A. A1 - Nair, G. B. A1 - Siddique, A. K. A1 - Sack, D. A. A1 - Ahsan, S. A1 - Huq, A. A1 - Sack, R. B. A1 - Rita R. Colwell A1 - others, AB - It has long been assumed that prolonged holding of environmental samples at the ambient air temperature prior to bacteriological analysis is detrimental to isolation and detection of Vibrio cholerae, the causative agent of pandemic cholera. The present study was aimed at understanding the effect of transporting environmental samples at the ambient air temperature on isolation and enumeration of V. cholerae. For water and plankton samples held at ambient temperatures ranging from 31°C to 35°C for 20 h, the total counts did not increase significantly but the number of culturable V. cholerae increased significantly compared to samples processed within 1 h of collection, as measured by culture, acridine orange direct count, direct fluorescent-antibody-direct viable count (DFA-DVC), and multiplex PCR analyses. For total coliform counts, total bacterial counts, and DFA-DVC counts, the numbers did not increase significantly, but the culturable plate counts for V. cholerae increased significantly after samples were held at the ambient temperature during transport to the laboratory for analysis. An increase in the recovery of V. cholerae O1 and improved detection of V. cholerae O1 rfb and ctxA also occurred when samples were enriched after they were kept for 20 h at the ambient temperature during transport. Improved detection and isolation of toxigenic V. cholerae from freshwater ecosystems can be achieved by holding samples at the ambient temperature, an observation that has significant implications for tracking this pathogen in diverse aquatic environments. VL - 72 ER - TY - JOUR T1 - Evolution of non-LTR retrotransposons in the trypanosomatid genomes: Leishmania major has lost the active elements JF - Molecular and Biochemical ParasitologyMolecular and Biochemical Parasitology Y1 - 2006 A1 - Bringaud, Frederic A1 - Ghedin, Elodie A1 - Blandin, Gaëlle A1 - Bartholomeu, Daniella C. A1 - Caler, Elisabet A1 - Levin, Mariano J. A1 - Baltz, Théo A1 - Najib M. El‐Sayed KW - Degenerate retroelement KW - Evolution KW - Ingi KW - L1Tc KW - Leishmania major KW - Non-LTR retrotransposon KW - Retroposon KW - Trypanosoma brucei KW - Trypanosoma cruzi AB - The ingi and L1Tc non-LTR retrotransposons - which constitute the ingi clade - are abundant in the genome of the trypanosomatid species Trypanosoma brucei and Trypanosoma cruzi, respectively. The corresponding retroelements, however, are not present in the genome of a closely related trypanosomatid, Leishmania major. To study the evolution of non-LTR retrotransposons in trypanosomatids, we have analyzed all ingi/L1Tc elements and highly degenerate ingi/L1Tc-related sequences identified in the recently completed T. brucei, T. cruzi and L. major genomes. The coding sequences of 242 degenerate ingi/L1Tc-related elements (DIREs) in all three genomes were reconstituted by removing the numerous frame shifts. Three independent phylogenetic analyses conducted on the conserved domains encoded by these elements show that all DIREs, including the 52 L. major DIREs, form a monophyletic group belonging to the ingi clade. This indicates that the trypanosomatid ancestor contained active mobile elements that have been retained in the Trypanosoma species, but were lost from L. major genome, where only remnants (DIRE) are detectable. All 242 DIREs analyzed group together according to their species origin with the exception of 11 T. cruzi DIREs which are close to the T. brucei ingi/DIRE families. Considering the absence of known horizontal transfer between the African T. brucei and the South-American T. cruzi, this suggests that this group of elements evolved at a lower rate when compared to the other trypanosomatid elements. Interestingly, the only nucleotide sequence conserved between ingi and L1Tc (the first 79 residues) is also present at the 5'-extremity of all the full length DIREs and suggests a possible role for this conserved motif, as well as for DIREs. VL - 145 SN - 0166-6851 ER - TY - JOUR T1 - Exopolysaccharide-associated protein sorting in environmental organisms: the PEP-CTERM/EpsH system. Application of a novel phylogenetic profiling heuristic JF - BMC biologyBMC biology Y1 - 2006 A1 - Haft, Daniel H. A1 - Paulsen, Ian T. A1 - Ward, Naomi A1 - J. Selengut KW - Amino Acid Motifs KW - Amino Acid Sequence KW - bacteria KW - Bacterial Proteins KW - Biofilms KW - Genome, Bacterial KW - Markov chains KW - Molecular Sequence Data KW - Phylogeny KW - Polysaccharides, Bacterial KW - Protein Sorting Signals KW - Protein Transport KW - Seawater KW - sequence alignment KW - Soil Microbiology AB - BACKGROUND: Protein translocation to the proper cellular destination may be guided by various classes of sorting signals recognizable in the primary sequence. Detection in some genomes, but not others, may reveal sorting system components by comparison of the phylogenetic profile of the class of sorting signal to that of various protein families. RESULTS: We describe a short C-terminal homology domain, sporadically distributed in bacteria, with several key characteristics of protein sorting signals. The domain includes a near-invariant motif Pro-Glu-Pro (PEP). This possible recognition or processing site is followed by a predicted transmembrane helix and a cluster rich in basic amino acids. We designate this domain PEP-CTERM. It tends to occur multiple times in a genome if it occurs at all, with a median count of eight instances; Verrucomicrobium spinosum has sixty-five. PEP-CTERM-containing proteins generally contain an N-terminal signal peptide and exhibit high diversity and little homology to known proteins. All bacteria with PEP-CTERM have both an outer membrane and exopolysaccharide (EPS) production genes. By a simple heuristic for screening phylogenetic profiles in the absence of pre-formed protein families, we discovered that a homolog of the membrane protein EpsH (exopolysaccharide locus protein H) occurs in a species when PEP-CTERM domains are found. The EpsH family contains invariant residues consistent with a transpeptidase function. Most PEP-CTERM proteins are encoded by single-gene operons preceded by large intergenic regions. In the Proteobacteria, most of these upstream regions share a DNA sequence, a probable cis-regulatory site that contains a sigma-54 binding motif. The phylogenetic profile for this DNA sequence exactly matches that of three proteins: a sigma-54-interacting response regulator (PrsR), a transmembrane histidine kinase (PrsK), and a TPR protein (PrsT). CONCLUSION: These findings are consistent with the hypothesis that PEP-CTERM and EpsH form a protein export sorting system, analogous to the LPXTG/sortase system of Gram-positive bacteria, and correlated to EPS expression. It occurs preferentially in bacteria from sediments, soils, and biofilms. The novel method that led to these findings, partial phylogenetic profiling, requires neither global sequence clustering nor arbitrary similarity cutoffs and appears to be a rapid, effective alternative to other profiling methods. VL - 4 N1 - http://www.ncbi.nlm.nih.gov/pubmed/16930487?dopt=Abstract ER - TY - JOUR T1 - eGenomics: Cataloguing our Complete Genome Collection JF - Comparative and functional genomicsComparative and functional genomics Y1 - 2005 A1 - Field, Dawn A1 - Garrity, George A1 - Morrison, Norman A1 - J. Selengut A1 - Sterk, Peter A1 - Tatusova, Tatiana A1 - Thomson, Nick VL - 6 N1 - http://www.ncbi.nlm.nih.gov/pubmed/18629208?dopt=Abstract ER - TY - JOUR T1 - Enhanced position weight matrices using mixture models JF - BioinformaticsBioinformatics Y1 - 2005 A1 - Sridhar Hannenhalli A1 - Wang, L. S. AB - Motivation: Positional weight matrix (PWM) is derived from a set of experimentally determined binding sites. Here we explore whether there exist subclasses of binding sites and if the mixture of these subclass-PWMs can improve the binding site prediction. Intuitively, the subclasses correspond to either distinct binding preference of the same transcription factor in different contexts or distinct subtypes of the transcription factor.Result: We report an Expectation Maximization algorithm adapting the mixture model of Baily and Elkan. We assessed the relative merit of using two subclass-PWMs. The resulting PWMs were evaluated with respect to preferred conservation (relative to mouse) of potential sites in human promoters and expression coherence of the potential target genes. Based on 64 JASPAR vertebrate PWMs, 61–81% of the cases resulted in a higher conservation using the mixture model. Also in 98% of the cases the expression coherence was higher for the target genes of one of the subclass-PWMs. Our analysis of Reb1 sites is consistent with previously discovered subtypes using independent methods. Additionally application of our method to mutated sites for transcription factor LEU3 reveals subclasses that segregate into strongly binding and weakly binding sites with P-value of 0.008. This is the first study which attempts to quantify the subtly different binding specificities of a transcription factor on a large scale and suggests the use of a mixture of PWMs, instead of the current practice of using a single PWM, for a transcription factor. VL - 21 SN - 1367-4803, 1460-2059 ER - TY - JOUR T1 - Effectiveness of conservation targets in capturing genetic diversity JF - Conserv BiolConserv Biol Y1 - 2003 A1 - Neel, M. C. A1 - Michael P. Cummings AB - Any conservation actions that preserve some populations and not others will have genetic consequences. We used empirical data from four rare plant taxa to assess these consequences in terms of how well allele numbers ( all alleles and alleles occurring at a frequency openface>0.05 in any population ) and expected heterozygosity are represented when different numbers of populations are conserved. We determined sampling distributions for these three measures of genetic diversity using Monte Carlo methods. We assessed the proportion of alleles included in the number of populations considered adequate for conservation, needed to capture all alleles, and needed to meet an accepted standard of genetic-diversity conservation of having a 90-95% probability of including all common alleles. We also assessed the number of populations necessary to obtain values of heterozygosity within +/-10% of the value obtained from all populations. Numbers of alleles were strongly affected by the number of populations sampled. Heterozygosity was only slightly less sensitive to numbers of populations than were alleles. On average, currently advocated conservation intensities represented 67-83% of all alleles and 85-93% of common alleles. The smallest number of populations to include all alleles ranged from 6 to 17 ( 42-57% ), but <0.2% of 1000 samples of these numbers of populations included them all. It was necessary to conserve 16-29 ( 53-93% ) of the sampled populations to meet the standard for common alleles. Between 20% and 64% of populations were needed to reliably represent species-level heterozygosity. Thus, higher percentages of populations are needed than are currently considered adequate to conserve genetic diversity if populations are selected without genetic data. VL - 17 ER - TY - CONF T1 - Efficient particle filter-based tracking of multiple interacting targets using an mrf-based motion model T2 - 2003 IEEE/RSJ International Conference on Intelligent Robots and Systems (IROS 2003) (Cat. No.03CH37453)Proceedings 2003 IEEE/RSJ International Conference on Intelligent Robots and Systems (IROS 2003) (Cat. No.03CH37453) Y1 - 2003 A1 - Khan, Z. A1 - Balch, T. A1 - Dellaert, F. JA - 2003 IEEE/RSJ International Conference on Intelligent Robots and Systems (IROS 2003) (Cat. No.03CH37453)Proceedings 2003 IEEE/RSJ International Conference on Intelligent Robots and Systems (IROS 2003) (Cat. No.03CH37453) PB - IEEE CY - Las Vegas, Nevada, USA UR - http://ieeexplore.ieee.org/lpdocs/epic03/wrapper.htm?arnumber=1250637 M3 - 10.1109/IROS.2003.1250637 ER - TY - JOUR T1 - Emergence and Evolution of Vibrio Cholerae O139 JF - Proceedings of the National Academy of SciencesPNASProceedings of the National Academy of SciencesPNAS Y1 - 2003 A1 - Faruque, Shah M. A1 - Sack, David A. A1 - Sack, R. Bradley A1 - Rita R. Colwell A1 - Takeda, Yoshifumi A1 - Nair, G. Balakrish AB - The emergence of Vibrio cholerae O139 Bengal during 1992–1993 was associated with large epidemics of cholera in India and Bangladesh and, initially, with a total displacement of the existing V. cholerae O1 strains. However, the O1 strains reemerged in 1994 and initiated a series of disappearance and reemergence of either of the two serogroups that was associated with temporal genetic and phenotypic changes sustained by the strains. Since the initial emergence of the O139 vibrios, new variants of the pathogen derived from multiple progenitors have been isolated and characterized. The clinical and epidemiological characteristics of these strains have been studied. Rapid genetic reassortment in O139 strains appears to be a response to the changing epidemiology of V. cholerae O1 and also a strategy for persistence in competition with strains of the O1 serogroup. The emergence of V. cholerae O139 has provided a unique opportunity to witness genetic changes in V. cholerae that may be associated with displacement of an existing serogroup by a newly emerging one and, thus, provide new insights into the epidemiology of cholera. The genetic changes and natural selection involving both environmental and host factors are likely to influence profoundly the genetics, epidemiology, and evolution of toxigenic V. cholerae, not only in the Ganges Delta region of India and Bangladesh, but also in other areas of endemic and epidemic cholera. VL - 100 SN - 0027-8424, 1091-6490 ER - TY - JOUR T1 - Effects of Global Climate on Infectious Disease: The Cholera Model JF - Clinical Microbiology ReviewsClin. Microbiol. Rev.Clinical Microbiology ReviewsClin. Microbiol. Rev. Y1 - 2002 A1 - Lipp, Erin K. A1 - Huq, Anwar A1 - Rita R. Colwell AB - Recently, the role of the environment and climate in disease dynamics has become a subject of increasing interest to microbiologists, clinicians, epidemiologists, and ecologists. Much of the interest has been stimulated by the growing problems of antibiotic resistance among pathogens, emergence and/or reemergence of infectious diseases worldwide, the potential of bioterrorism, and the debate concerning climate change. Cholera, caused by Vibrio cholerae, lends itself to analyses of the role of climate in infectious disease, coupled to population dynamics of pathogenic microorganisms, for several reasons. First, the disease has a historical context linking it to specific seasons and biogeographical zones. In addition, the population dynamics of V. cholerae in the environment are strongly controlled by environmental factors, such as water temperature, salinity, and the presence of copepods, which are, in turn, controlled by larger-scale climate variability. In this review, the association between plankton and V. cholerae that has been documented over the last 20 years is discussed in support of the hypothesis that cholera shares properties of a vector-borne disease. In addition, a model for environmental transmission of cholera to humans in the context of climate variability is presented. The cholera model provides a template for future research on climate-sensitive diseases, allowing definition of critical parameters and offering a means of developing more sophisticated methods for prediction of disease outbreaks. VL - 15 SN - 0893-8512, 1098-6618 ER - TY - JOUR T1 - Evidence for a plastid origin of plant ethylene receptor genes. JF - Plant Physiol Y1 - 2002 A1 - Mount, Stephen M A1 - Chang, Caren KW - Amino Acid Sequence KW - Anabaena KW - Arabidopsis KW - Cyanobacteria KW - Molecular Sequence Data KW - Plant Proteins KW - Plastids KW - Protein Kinases KW - Receptors, Cell Surface KW - Sequence Homology, Amino Acid VL - 130 CP - 1 M3 - 10.1104/pp.005397 ER - TY - Generic T1 - Experimental Construction of Very Large Scale DNA Databases with Associative Search T2 - DNA computing: 7th International Workshop on DNA-Based Computers, DNA 7, Tampa, FL, USA, June 10-13, 2001: revised papers Y1 - 2002 A1 - Reif, J. H. A1 - LaBean, T. H. A1 - Pirrung, M. A1 - Rana, V. S. A1 - Guo, B. A1 - Kingsford, Carl A1 - Wickham, G. S. JA - DNA computing: 7th International Workshop on DNA-Based Computers, DNA 7, Tampa, FL, USA, June 10-13, 2001: revised papers VL - 7 ER - TY - Generic T1 - Efficient perspective-accurate silhouette computation and applications T2 - Proceedings of the seventeenth annual symposium on Computational geometry Y1 - 2001 A1 - M. Pop A1 - Duncan, Christian A1 - Barequet, Gill A1 - Goodrich, Michael A1 - Huang, Wenjing A1 - Kumar, Subodh KW - rendering KW - silhouette KW - simplification AB - Silhouettes are perceptually and geometrically salient features of geo metric models. Hence a number of graphics and visualization applications need to find them to aid further processing. The efficient computation of silhouettes, especially in the context of perspective projection, is known to be difficult. This paper presents a novel efficient and practical algorithm to compute silhouettes from a sequence of viewpoints under perspective projection. Parallel projection is a special case of this algorithm. Our approach is based on a point-plane duality in three dimensions, which allows an efficient computation of the \emph{changes} in the silhouette of a polygonal model between consecutive frames. In addition, we present several applications of our technique to problems from computer graphics and medical visualization. We also provide experimental data that show the efficiency of our approach. million vertices on an SGI Onyx workstation. JA - Proceedings of the seventeenth annual symposium on Computational geometry T3 - SCG '01 PB - ACM CY - New York, NY, USA SN - 1-58113-357-X ER - TY - JOUR T1 - Enrichment of Regulatory Signals in Conserved Non-Coding Genomic Sequence JF - BioinformaticsBioinformaticsBioinformaticsBioinformatics Y1 - 2001 A1 - Levy, Samuel A1 - Sridhar Hannenhalli A1 - Workman, Christopher AB - Motivation: Whole genome shotgun sequencing strategies generate sequence data prior to the application of assembly methodologies that result in contiguous sequence. Sequence reads can be employed to indicate regions of conservation between closely related species for which only one genome has been assembled. Consequently, by using pairwise sequence alignments methods it is possible to identify novel, non-repetitive, conserved segments in non-coding sequence that exist between the assembled human genome and mouse whole genome shotgun sequencing fragments. Conserved non-coding regions identify potentially functional DNA that could be involved in transcriptional regulation.Results: Local sequence alignment methods were applied employing mouse fragments and the assembled human genome. In addition, transcription factor binding sites were detected by aligning their corresponding positional weight matrices to the sequence regions. These methods were applied to a set of transcripts corresponding to 502 genes associated with a variety of different human diseases taken from the Online Mendelian Inheritance in Man database. Using statistical arguments we have shown that conserved non-coding segments contain an enrichment of transcription factor binding sites when compared to the sequence background in which the conserved segments are located. This enrichment of binding sites was not observed in coding sequence. Conserved non-coding segments are not extensively repeated in the genome and therefore their identification provides a rapid means of finding genes with related conserved regions, and consequently potentially related regulatory mechanism. Conserved segments in upstream regions are found to contain binding sites that are co-localized in a manner consistent with experimentally known transcription factor pairwise co-occurrences and afford the identification of novel co-occurring Transcription Factor (TF) pairs. This study provides a methodology and more evidence to suggest that conserved non-coding regions are biologically significant since they contain a statistical enrichment of regulatory signals and pairs of signals that enable the construction of regulatory models for human genes. Contact: samuel.levy@celera.com VL - 17 SN - 1367-4803, 1460-2059 ER - TY - JOUR T1 - Expanding the definition of informational suppression. JF - Trends Genet Y1 - 2000 A1 - Mount, S M A1 - Anderson, P KW - Animals KW - DNA-Binding Proteins KW - Drosophila Proteins KW - Nuclear Proteins KW - Recombinant Proteins KW - Repressor Proteins KW - Suppression, Genetic KW - Transcription Factors VL - 16 CP - 4 ER - TY - JOUR T1 - Exploiting coherence in spatial database queries Y1 - 2000 A1 - M. Pop A1 - Adviser-Kosaraju, S. R. PB - The Johns Hopkins University ER - TY - JOUR T1 - The effect of calprotectin on the nucleation and growth of struvite crystals as assayed by light microscopy in real-time JF - The Journal of urologyThe Journal of urology Y1 - 1998 A1 - Asakura, H. A1 - J. Selengut A1 - Orme-Johnson, W. H. A1 - Dretler, S. P. KW - Crystallization KW - Dose-Response Relationship, Drug KW - Leukocyte L1 Antigen Complex KW - Magnesium Compounds KW - Neural Cell Adhesion Molecules KW - Phosphates KW - Time factors AB - PURPOSE: To use light microscopy to observe the urease-induced growth of struvite crystals in real-time, and to compare the effects of various proteins on that growth. MATERIALS AND METHODS: Artificial urine, with and without citrate, and a minimal urine solution containing only urea and the components of struvite and apatite were incubated with urease and test proteins in the depressions of culture slides. The number and size of rectangular and X-shaped struvite crystals were recorded using a low-power phase contrast microscope. RESULTS: The formation of crystalline struvite appears to occur after the formation of an amorphous calcium- and magnesium-containing phase. The extent of this amorphous phase is dependent on the presence of calcium and citrate, both of which strongly promote its formation over the crystalline phase. alpha-globulin, gamma-globulin and chymotrypsin inhibitor all result in the same amount of crystalline struvite as bovine serum albumin which is used as a control. Calprotectin, on the other hand, causes consistent and significant reductions in the number and size of struvite crystals under a wide range of conditions. No changes in the morphology of the struvite crystals were observed. CONCLUSIONS: Calprotectin, the dominant protein of infection stone matrix, has distinctive properties which affect the formation and growth of struvite crystals. The presence of citrate in synthetic urine dramatically reduces the number of struvite crystals observed. The present method for observing the effects of putative infection stone inhibitors appears to have merit. VL - 159 N1 - http://www.ncbi.nlm.nih.gov/pubmed/9507889?dopt=Abstract ER - TY - JOUR T1 - The evolution of plant nuclear genes JF - Proc Natl Acad Sci USAProc Natl Acad Sci USA Y1 - 1997 A1 - Clegg, M. T. A1 - Michael P. Cummings A1 - Durbin, M. L. AB - We analyze the evolutionary dynamics of three of the best-studied plant nuclear multigene families. The data analyzed derive from the genes that encode the small subunit of ribulose-1,5-bisphosphate carboxylase (rbcS), the gene family that encodes the enzyme chalcone synthase (Chs), and the gene family that encodes alcohol dehydrogenases (Adh). In addition, we consider the limited evolutionary data available on plant transposable elements. New Chs and rbcS genes appear to be recruited at about 10 times the rate estimated for Adh genes, and this is correlated with a much smaller average gene family size for Adh genes. In addition, duplication and divergence in function appears to be relatively common for Chs genes in flowering plant evolution. Analyses of synonymous nucleotide substitution rates for Adh genes in monocots reject a linear relationship with clock time. Replacement substitution rates vary with time in a complex fashion, which suggests that adaptive evolution has played an important role in driving divergence following gene duplication events. Molecular population genetic studies of Adh and Chs genes reveal high levels of molecular diversity within species. These studies also reveal that inter- and intralocus recombination are important forces in the generation allelic novelties. Moreover, illegitimate recombination events appear to be an important factor in transposable element loss in plants. When we consider the recruitment and loss of new gene copies, the generation of allelic diversity within plant species, and ectopic exchange among transposable elements, we conclude that recombination is a pervasive force at all levels of plant evolution. VL - 94 ER - TY - JOUR T1 - Evolutionary biology of parasitic platyhelminths: The role of molecular phylogenetics JF - Parasitol TodayParasitol Today Y1 - 1996 A1 - Blair, D. A1 - Campos, A. A1 - Michael P. Cummings A1 - Laclette, J. P. AB - As our appreciation of the diversity within the flatworms has grown, so too has our curiosity about the ways in which these varied creatures are related to one another. In particular, the parasitic groups (trematodes, cestodes and monogeneans have been the focus of enquiry. Until recently, morphology, anatomy and life histories have provided the raw data for building hypotheses on relationships. Now, ultrastructural evidence, and most recently, molecular data from nucleic acid sequences, have been brought to bear on the topic. Here, David Blair, Andrés Campos, Michael Cummings and Juan Pedro Laclette discuss the ways in which molecular data, in particular, are helping us recognize the various lineages of flatworms. VL - 12 ER - TY - Generic T1 - Efficient algorithms for computing matching and chromatic polynomials on series-parallel graphs T2 - Fourth International Conference on Computing and Information, 1992. Proceedings. ICCI '92 Y1 - 1992 A1 - Chandrasekharan, N. A1 - Sridhar Hannenhalli KW - chromatic polynomials KW - computational complexity KW - Computer science KW - graph colouring KW - graph theory KW - matching polynomial KW - Polynomials KW - series-parallel graphs KW - Terminology KW - Tree data structures KW - Tree graphs AB - The authors present efficient algorithms for computing the matching polynomial and chromatic polynomial of a series-parallel graph in O(n3) and O(n2) time respectively. Their algorithm for computing the matching polynomial generalizes an existing result from Lovasz, Plummer (1986) and the chromatic polynomial algorithm improves the result given by Hunt, Ravi, Stearn (1988) from O(n4) time JA - Fourth International Conference on Computing and Information, 1992. Proceedings. ICCI '92 PB - IEEE SN - 0-8186-2812-X ER - TY - JOUR T1 - Evolution of avocados as revealed by DNA restriction fragment variation JF - J HeredJ Hered Y1 - 1990 A1 - Furnier, G. R. A1 - Michael P. Cummings A1 - Clegg, M. T. AB - Individuals representing the genus ıt Persea, subgenus ıt Persea were assayed for restriction fragment length polymorphisms in their chloroplast genome, nuclear ribosomal DNA, and the genes coding for the enzyme cellulase. The subgenus ıt Persea appears to consist of ıt P. schiedeana and a separate taxon containing the remaining species. ıt P. americana does not appear to be a monophyletic group. If ıt P. americana is to be maintained as a species containing var. ıt americana, var. ıt drymifolia, and var. ıt guatemalensis, then our data suggest that it should also contain varieties corresponding to ıt P. floccosa, ıt P. nubigena, and ıt P. steyermarkii. ıt P. americana var. ıt guatemalensis appears to have originated as a hybrid between ıt P. steyermarkii and ıt P. nubigena. The root-rot-resistant cultivar G755A is a hybrid progeny of ıt P. schiedeana and ıt P. americana var. guatemalensis. The three varieties of ıt P. americana were all distinguished by mutations. VL - 81 ER -