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PyCogent: a toolkit for making sense from sequence

GENOME BIOLOGY 2007年第8期8卷 1-16页

作者： Knight, Rob Maxwell, Peter Birmingham, Amanda Carnes, Jason Caporaso, J. Gregory Easton, Brett C. Eaton, Michael Hamady, Micah Lindsay, Helen Liu, Zongzhi Lozupone, Catherine McDonald, Daniel Robeson, Michael Sammut, Raymond Smit, Sandra Wakefield, Matthew J. Widmann, Jeremy Wikman, Shandy Wilson, Stephanie Ying, Hua Huttley, Gavin A. Univ Colorado Dept Chem & Biochem Boulder CO 80309 USA Australian Natl Univ John Curtin Sch Med Res Computat Genom Lab Canberra ACT 2601 Australia Thermo Fisher Sci Lafayette CO USA Seattle Biomed Res Inst Seattle WA 98109 USA Univ Colorado Hlth Sci Ctr Dept Biochem & Mol Genet Aurora CO USA Sci Applicat Int Corp Englewood CO USA Univ Colorado Dept Comp Sci Boulder CO 80309 USA Univ Colorado Dept Ecol & Evolut Biol Boulder CO 80309 USA Walter & Eliza Hall Inst Med Res Melbourne Vic 3050 Australia

We have implemented in Python the COmparative GENomic Toolkit, a fully integrated and thoroughly tested framework for novel probabilistic analyses of biological sequences, devising workflows, and generating publication quality graphics. PyCogent includes connectors to remote databases, built-in generalized probabilistic techniques for working with biological sequences, and controllers for third-party applications. The toolkit takes advantage of parallel architectures and runs on a range of hardware and operating systems, and is available under the general public license from http://***/projects/pycogent.

关键词： Protein data Bank additional data file Substitution Model Application Programming Interface Basic Local Alignment Search Tool

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The relationships between the isoelectric point and: length of proteins, taxonomy and ecology of organisms

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BMC GENOMICS 2007年第1期8卷 1-16页

作者： Kiraga, Joanna Mackiewicz, Pawel Mackiewicz, Dorota Kowalczuk, Maria Biecek, Przemyslaw Polak, Natalia Smolarczyk, Kamila Dudek, Miroslaw R. Cebrat, Stanislaw Univ Wroclaw Dept Genom PL-51148 Wroclaw Poland Univ Zielona Gora Inst Phys PL-65516 Zielona Gora Poland

Background: The distribution of isoelectric point (pl) of proteins in a proteome is universal for all organisms. It is bimodal dividing the proteome into two sets of acidic and basic proteins. Different species however have different abundance of acidic and basic proteins that may be correlated with taxonomy, subcellular localization, ecological niche of organisms and proteome size. Results: We have analysed 1784 proteomes encoded by chromosomes of Archaea, Bacteria, Eukaryota, and also mitochondria, plastids, prokaryotic plasmids, phages and viruses. We have found significant correlation in more than 95% of proteomes between the protein length and pl in proteomes -positive for acidic proteins and negative for the basic ones. Plastids, viruses and plasmids encode more basic proteomes while chromosomes of Archaea, Bacteria, Eukaryota, mitochondria and phages more acidic ones. Mitochondrial proteomes of Viridiplantae, Protista and Fungi are more basic than Metazoa. It results from the presence of basic proteins in the former proteomes and their absence from the latter ones and is related with reduction of metazoan genomes. Significant correlation was found between the pl bias of proteomes encoded by prokaryotic chromosomes and proteomes encoded by plasmids but there is no correlation between eukaryotic nuclear-coded proteomes and proteomes encoded by organelles. Detailed analyses of prokaryotic proteomes showed significant relationships between pl distribution and habitat, relation to the host cell and salinity of the environment, but no significant correlation with oxygen and temperature requirements. The salinity is positively correlated with acidicity of proteomes. Host-associated organisms and especially intracellular species have more basic proteomes than free-living ones. The higher rate of mutations accumulation in the intracellular parasites and endosymbionts is responsible for the basicity of their tiny proteomes that explains the observed positive correlatio

关键词： Basic Protein additional data file Intracellular Bacterium Orthologous Protein Mutational Pressure

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Analysis of the platypus genome suggests a transposon origin for mammalian imprinting

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GENOME BIOLOGY 2009年第1期10卷 1-8页

作者： Pask, Andrew J. Papenfuss, Anthony T. Ager, Eleanor I. Mccoll, Kaighin A. Speed, Terence P. Renfree, Marilyn B. Univ Melbourne Dept Zool Melbourne Vic 3010 Australia Univ Connecticut Dept Mol & Cellular Biol Storrs CT 06269 USA Walter & Eliza Hall Inst Med Res Bioinformat Div Parkville Vic 3050 Australia

Background: Genomic imprinting is an epigenetic phenomenon that results in monoallelic gene expression. Many hypotheses have been advanced to explain why genomic imprinting evolved in mammals, but few have examined how it arose. The host defence hypothesis suggests that imprinting evolved from existing mechanisms within the cell that act to silence foreign DNA elements that insert into the genome. However, the changes to the mammalian genome that accompanied the evolution of imprinting have been hard to define due to the absence of large scale genomic resources between all extant classes. The recent release of the platypus genome has provided the first opportunity to perform comparisons between prototherian (monotreme;which appear to lack imprinting) and therian (marsupial and eutherian;which have imprinting) mammals. Results: We compared the distribution of repeat elements known to attract epigenetic silencing across the entire genome from monotremes and therian mammals, particularly focusing on the orthologous imprinted regions. There is a significant accumulation of certain repeat elements within imprinted regions of therian mammals compared to the platypus. Conclusions: Our analyses show that the platypus has significantly fewer repeats of certain classes in the regions of the genome that have become imprinted in therian mammals. The accumulation of repeats, especially long terminal repeats and DNA elements, in therian imprinted genes and gene clusters is coincident with, and may have been a potential driving force in, the development of mammalian genomic imprinting. These data provide strong support for the host defence hypothesis.

关键词： additional data file Imprint Gene Repeat Element Chicken Genome Orthologous Region

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Association of common polymorphisms in known susceptibility genes with rheumatoid arthritis in a Slovak population using osteoarthritis patients as controls

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ARTHRITIS RESEARCH & THERAPY 2009年第3期11卷 1-10页

作者： Stark, Klaus Rovensky, Jozef Blazickova, Stanislava Grosse-Wilde, Hans Ferencik, Stanislav Hengstenberg, Christian Straub, Rainer H. Univ Hosp Regensburg Dept Internal Med 2 D-93042 Regensburg Germany Univ Hosp Regensburg Dept Internal Med 1 D-93042 Regensburg Germany Univ Hosp Essen Inst Immunol D-45122 Essen Germany Natl Inst Rheumat Dis Piestany 92123 Slovakia

Introduction Both genetic and environmental factors contribute to rheumatoid arthritis ( RA), a common and complex autoimmune disease. As well as the major susceptibility gene HLA-DRB1, recent genome-wide and candidate-gene studies reported additional evidence for association of single nucleotide polymorphism (SNP) markers in the PTPN22, STAT4, OLIG3/TNFAIP3 and TRAF1/C5 loci with RA. This study was initiated to investigate the association between defined genetic markers and RA in a Slovak population. In contrast to recent studies, we included intensively-characterized osteoarthritis (OA) patients as controls. Methods We used material of 520 RA and 303 OA samples in a case-control setting. Six SNPs were genotyped using TaqMan assays. HLA-DRB1 alleles were determined by employing site-specific polymerase chain reaction (PCR) amplification. Results No statistically significant association of TRAF1/C5 SNPs rs3761847 and rs10818488 with RA was detected. However, we were able to replicate the association signals between RA and HLA-DRB1 alleles, STAT4 (rs7574865), PTPN22 (rs2476601) and OLIG3/TNFAIP3 (rs10499194 and rs6920220). The strongest signal was detected for HLA-DRB1*04 with an allelic P = 1.2*10(-13) (OR = 2.92, 95% confidence interval (CI) = 2.18 - 3.91). additionally, SNPs rs7574865(STAT4) (P = 9.2*10(-6);OR = 1.71, 95% CI = 1.35 2.18) and rs2476601(PTPN22) (P = 9.5*10(-4);OR = 1.67, 95% CI = 1.23 - 2.26) were associated with susceptibility to RA, whereas after permutation testing OLIG3/TNFAIP3 SNPs rs10499194 and rs6920220 missed our criteria for significance (P-corr = 0.114 and P-corr = 0.180, respectively). Conclusions In our Slovak population, HLA-DRB1 alleles as well as SNPs in STAT4 and PTPN22 genes showed a strong association with RA.

关键词： Rheumatoid Arthritis Human Leukocyte Antigen additional data file Single Nucleotide Polymorphism Marker Share Epitope

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Association between breast cancer susceptibility loci and mammographic density: the Multiethnic Cohort

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BREAST CANCER RESEARCH 2009年第1期11卷 1-7页

作者： Woolcott, Christy G. Maskarinec, Gertraud Haiman, Christopher A. Verheus, Martijn Pagano, Ian S. Le Marchand, Loic Henderson, Brian E. Kolonel, Laurence N. Univ Hawaii Canc Res Ctr Hawaii Honolulu HI 96813 USA Univ So Calif Keck Sch Med Kenneth Norris Jr Comprehens Canc Ctr Dept Prevent Med Los Angeles CA 90089 USA

Introduction Mammographic density is a strong risk factor for breast cancer. Our objective was to examine its association with polymorphisms identifying breast cancer susceptibility loci that were ascertained in recent genome-wide association studies. Methods Subjects were 825 women who participated in previous case - control studies of mammographic density and genetic factors nested within the Multiethnic Cohort study and were from three ethnic groups (White, Japanese American, Native Hawaiian). Eight polymorphisms (rs2981582 in FGFR2, rs3803662 and rs12443621in TOX3, rs3817198 in LSP1, rs981782 and rs10941679 near HCN1/MRPS30, rs889312 in MAP3K1, and rs13387042 at 2q) were examined. Mammographic density was quantified with a computer-assisted method as the percent dense area: the area of radiologically dense fibroglandular tissue relative to the total breast area that also includes radiologically lucent fatty tissue. Results The polymorphism rs12443621 in TOX3 was associated with percent dense area;women with at least one G allele ( previously associated with increased breast cancer risk) had 3% to 4% higher densities than women with two A alleles. The polymorphism rs10941679 near HCN1/MRPS30 was also associated with percent dense area;women who were homozygous for the G allele (previously associated with increased breast cancer risk) had 4% to 5% lower densities than women with at least one A allele. The other polymorphisms were not associated with percent dense area. Conclusions The available data suggest that the effects of most of these polymorphisms on breast cancer are not mediated by mammographic density. Some effects may have been too small to be detected. The association with rs12443621 may provide clues as to how variation in TOX3 influences breast cancer risk.

关键词： Breast Cancer Breast Cancer Risk Hormone Replacement Therapy Menopausal Status additional data file

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Evidence for horizontal transfer of a secondary metabolite gene cluster between fungi

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GENOME BIOLOGY 2008年第1期9卷 1-10页

作者： Khaldi, Nora Collemare, Jerome Lebrun, Marc-Henri Wolfe, Kenneth H. Univ Dublin Trinity Coll Smurfit Inst Genet Dublin 2 Ireland BCS INSA UCB UMR CNRS 5240 F-69263 Lyon 09 France

Background: Filamentous fungi synthesize many secondary metabolites and are rich in genes encoding proteins involved in their biosynthesis. Genes from the same pathway are often clustered and co-expressed in particular conditions. Such secondary metabolism gene clusters evolve rapidly through multiple rearrangements, duplications and losses. It has long been suspected that clusters can be transferred horizontally between species, but few concrete examples have been described so far. Results: In the rice blast fungus Magnaporthe grisea, the avirulence gene ACEI that codes for a hybrid polyketide synthase-nonribosomal peptide synthetase (PKS-NRPS) belongs to a cluster of 15 genes involved in secondary metabolism. additional related clusters were detected in the ascomycetes Chaetomium globosum, Stagonospora nodorum and Aspergillus clavatus. Gene-by-gene phylogenetic analysis showed that in C. globosum and M. grisea, the evolution of these ACEI-like clusters is characterized by successive complex duplication events including tandem duplication within the M. grisea cluster. The phylogenetic trees also present evidence that at least five of the six genes in the homologous ACEI gene cluster in A. clavatus originated by horizontal transfer from a donor closely related to M. grisea. Conclusion: The ACEI cluster originally identified in M. grisea is shared by only few fungal species. Its sporadic distribution within euascomycetes is mainly explained by multiple events of duplication and losses. However, because A. clavatus contains an ACEI cluster of only six genes, we propose that horizontal transfer from a relative of M. grisea into an ancestor of A. clavatus provides a much simpler explanation of the observed data than the alternative of multiple events of duplication and losses of parts of the cluster.

关键词： Horizontal Gene Transfer additional data file Tandem Duplication Rice Blast Fungus Chaetomium Globosum

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Porcine transcriptome analysis based on 97 non-normalized cDNA libraries and assembly of 1,021,891 expressed sequence tags

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GENOME BIOLOGY 2007年第4期8卷 1-16页

作者： Gorodkin, Jan Cirera, Susanna Hedegaard, Jakob Gilchrist, Michael J. Panitz, Frank Jorgensen, Claus Scheibye-Knudsen, Karsten Arvin, Troels Lumholdt, Steen Sawera, Milena Green, Trine Nielsen, Bente J. Havgaard, Jakob H. Rosenkilde, Carina Wang, Jun Li, Heng Li, Ruiqiang Liu, Bin Hu, Songnian Dong, Wei Li, Wei Yu, Jun Wang, Jian Staerfeldt, Hans-Henrik Wernersson, Rasmus Madsen, Lone B. Thomsen, Bo Hornshoj, Henrik Zhan Bujie Wang, Xuegang Wang, Xuefei Bolund, Lars Brunak, Soren Yang, Huanming Bendixen, Christian Fredholm, Merete Royal Vet & Agr Univ IBHV Div Genet & Bioinformat DK-1870 Frederiksberg C Denmark Danish Inst Agr Sci Dept Genet & Biotechnol DK-8830 Tjele Denmark Wellcome Trust Canc Res UK Gurdon Inst Cambridge CB2 1QN England Beijing Genom Inst Beijing 101300 Peoples R China Univ Aarhus Inst Human Genet DK-8000 Aarhus C Denmark Univ So Denmark Dept Biochem & Mol Biol DK-5230 Odense M Denmark BioCtr DTU Ctr Biol Sequence Anal DK-2800 Lyngby Denmark

Background: Knowledge of the structure of gene expression is essential for mammalian transcriptomics research. We analyzed a collection of more than one million porcine expressed sequence tags ( ESTs), of which two-thirds were generated in the Sino-Danish Pig Genome Project and one-third are from public databases. The Sino-Danish ESTs were generated from one normalized and 97 non-normalized cDNA libraries representing 35 different tissues and three developmental stages. Results: Using the Distiller package, the ESTs were assembled to roughly 48,000 contigs and 73,000 singletons, of which approximately 25% have a high confidence match to UniProt. Approximately 6,000 new porcine gene clusters were identified. Expression analysis based on the non-normalized libraries resulted in the following findings. The distribution of cluster sizes is scaling invariant. Brain and testes are among the tissues with the greatest number of different expressed genes, whereas tissues with more specialized function, such as developing liver, have fewer expressed genes. There are at least 65 high confidence housekeeping gene candidates and 876 cDNA library-specific gene candidates. We identified differential expression of genes between different tissues, in particular brain/spinal cord, and found patterns of correlation between genes that share expression in pairs of libraries. Finally, there was remarkable agreement in expression between specialized tissues according to Gene Ontology categories. Conclusion: This EST collection, the largest to date in pig, represents an essential resource for annotation, comparative genomics, assembly of the pig genome sequence, and further porcine transcription studies.

关键词： Gene Ontology cDNA Library additional data file Library Size Match Level

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Ulysses - an application for the projection of molecular interactions across species

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GENOME BIOLOGY 2005年第12期6卷 1-11页

作者： Kemmer, D Huang, Y Shah, SP Lim, J Brumm, J Yuen, MMS Ling, J Xu, T Wasserman, WW Ouellette, BFF Univ British Columbia Ctr Mol Med & Therapeut Vancouver BC V5Z 4H4 Canada Karolinska Inst Ctr Genom & Bioinformat S-17177 Stockholm Sweden Univ British Columbia UBC Bioinformat Ctr Vancouver BC V6T 1Z4 Canada Univ British Columbia Dept Med Genet Vancouver BC V5Z 1M9 Canada Univ British Columbia Michael Smith Labs Vancouver BC V6T 1Z4 Canada Univ British Columbia Dept Comp Sci Vancouver BC V6T 1Z4 Canada

We developed Ulysses as a user-oriented system that uses a process called Interolog Analysis for the parallel analysis and display of protein interactions detected in various species. Ulysses was designed to perform such Interolog Analysis by the projection of model organism interaction data onto homologous human proteins, and thus serves as an accelerator for the analysis of uncharacterized human proteins. The relevance of projections was assessed and validated against published reference collections. All source code is freely available, and the Ulysses system can be accessed via a web interface http://***/ulysses.

关键词： additional data file Structure Query Language Human Protein Reference database Protein Interaction data Functional Genomic data

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Divergence of exonic splicing elements after gene duplication and the impact on gene structures

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GENOME BIOLOGY 2009年第11期10卷 1-14页

作者： Zhang, Zhenguo Zhou, Li Wang, Ping Liu, Yang Chen, Xianfeng Hu, Landian Kong, Xiangyin Chinese Acad Sci SIBS Inst Hlth Sci Key Lab Stem Cell Biol Shanghai 200025 Peoples R China Shanghai Jiao Tong Univ Sch Med Shanghai 200025 Peoples R China Chinese Acad Sci Grad Sch Beijing 100049 Peoples R China Shanghai Jiao Tong Univ Ruijin Hosp State Key Lab Med Genom Shanghai 200025 Peoples R China

Background: The origin of new genes and their contribution to functional novelty has been the subject of considerable interest. There has been much progress in understanding the mechanisms by which new genes originate. Here we examine a novel way that new gene structures could originate, namely through the evolution of new alternative splicing isoforms after gene duplication. Results: We studied the divergence of exonic splicing enhancers and silencers after gene duplication and the contributions of such divergence to the generation of new splicing isoforms. We found that exonic splicing enhancers and exonic splicing silencers diverge especially fast shortly after gene duplication. About 10% and 5% of paralogous exons undergo significantly asymmetric evolution of exonic splicing enhancers and silencers, respectively. When compared to pre-duplication ancestors, we found that there is a significant overall loss of exonic splicing enhancers and the magnitude increases with duplication age. Detailed examination reveals net gains and losses of exonic splicing enhancers and silencers in different copies and paralog clusters after gene duplication. Furthermore, we found that exonic splicing enhancer and silencer changes are mainly caused by synonymous mutations, though nonsynonymous changes also contribute. Finally, we found that exonic splicing enhancer and silencer divergence results in exon splicing state transitions (from constitutive to alternative or vice versa), and that the proportion of paralogous exon pairs with different splicing states also increases over time, consistent with previous predictions. Conclusions: Our results suggest that exonic splicing enhancer and silencer changes after gene duplication have important roles in alternative splicing divergence and that these changes contribute to the generation of new gene structures.

关键词： Alternative Splice Gene Duplication additional data file Alternative Exon Exonic Splice Enhancer

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A compendium of Caenorhabditis elegans regulatory transcription factors:: a resource for mapping transcription regulatory networks

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GENOME BIOLOGY 2005年第13期6卷 1-12页

作者： Reece-Hoyes, John S. Deplancke, Bart Shingles, Jane Grove, Christian A. Hope, Ian A. Walhout, Albertha J. M. Univ Massachusetts Sch Med Program Gene Funct & Express Worcester MA 01605 USA Univ Leeds Sch Biol Fac Biol Sci Inst Integrat & Comparat Biol Leeds LS2 9JT W Yorkshire England Univ Massachusetts Sch Med Program Mol Med Worcester MA 01605 USA

Background: Transcription regulatory networks are composed of interactions between transcription factors and their target genes. Whereas unicellular networks have been studied extensively, metazoan transcription regulatory networks remain largely unexplored. Caenorhabditis elegans provides a powerful model to study such metazoan networks because its genome is completely sequenced and many functional genomic tools are available. While C. elegans gene predictions have undergone continuous refinement, this is not true for the annotation of functional transcription factors. The comprehensive identification of transcription factors is essential for the systematic mapping of transcription regulatory networks because it enables the creation of physical transcription factor resources that can be used in assays to map interactions between transcription factors and their target genes. Results: By computational searches and extensive manual curation, we have identified a compendium of 934 transcription factor genes ( referred to as wTF2.0). We find that manual curation drastically reduces the number of both false positive and false negative transcription factor predictions. We discuss how transcription factor splice variants and dimer formation may affect the total number of functional transcription factors. In contrast to mouse transcription factor genes, we find that C. elegans transcription factor genes do not undergo significantly more splicing than other genes. This difference may contribute to differences in organism complexity. We identify candidate redundant worm transcription factor genes and orthologous worm and human transcription factor pairs. Finally, we discuss how wTF2.0 can be used together with physical transcription factor clone resources to facilitate the systematic mapping of C. elegans transcription regulatory networks. Conclusion: wTF2.0 provides a starting point to decipher the transcription regulatory networks that control metazoan development and funct

关键词： Gene Ontology additional data file Nuclear Hormone Receptor Comprehensive Compendium Green Fluorescent Protein Construct

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