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The Alternative Splicing Mutation Database: A hub for investigations of alternative splicing using mutational evidence

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BMC Research Notes 2008年第1期1卷 1-7页

作者： Bechtel, Jason M. Rajesh, Preeti Ilikchyan, Irina Deng, Ying Mishra, Pankaj K. Wang, Qi Wu, Xiaochun Afonin, Kirill A. Grose, William E. Wang, Ye Khuder, Sadik Fedorov, Alexei Program in Bioinformatics and Proteomics/Genomics University of Toledo Health Science Campus Toledo OH 43614 United States Dept. of Medical Microbiology and Immunology University of Toledo Health Science Campus Toledo OH 43614 United States Dept. of Basic Pharmaceutical Sciences South Carolina College of Pharmacy University of South Carolina Columbia SC 29208 United States Department of Biological Sciences Bowling Green State University Bowling Green OH 43403 United States College of Engineering University of Toledo Toledo OH 43606 United States Dept. of Medicine University of Toledo Health Science Campus Toledo OH 43614 United States

Background. Some mutations in the internal regions of exons occur within splicing enhancers and silencers, influencing the pattern of alternative splicing in the corresponding genes. To understand how these sequence changes affect splicing, we created a database of these mutations. Findings. The Alternative Splicing Mutation Database (ASMD) serves as a repository for all exonic mutations not associated with splicing junctions that measurably change the pattern of alternative splicing. In this initial published release (version 1.2), only human sequences are present, but the ASMD will grow to include other organisms, (see Availability and requirements section for the ASMD web address). This relational database allows users to investigate connections between mutations and features of the surrounding sequences, including flanking sequences, RNA secondary structures and strengths of splice junctions. Splicing effects of the mutations are quantified by the relative presence of alternative mRNA isoforms with and without a given mutation. This measure is further categorized by the accuracy of the experimental methods employed. The database currently contains 170 mutations in 66 exons, yet these numbers increase regularly. We developed an algorithm to derive a table of oligonucleotide Splicing Potential (SP) values from the ASMD dataset. We present the SP concept and tools in detail in our corresponding article. Conclusion. The current data set demonstrates that mutations affecting splicing are located throughout exons and might be enriched within local RNA secondary structures. Exons from the ASMD have below average splicing junction strength scores, but the difference is small and is judged not to be significant. © 2008 Bechtel et al;licensee BioMed Central Ltd.

关键词： Alternative Splice Splice Effect Splice Junction Alternative Splice Effect mRNA Isoforms

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Calculation of splicing potential from the alternative splicing mutation database

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BMC Research Notes 2008年第1期1卷 1-6页

Background. The Alternative Splicing Mutation Database (ASMD) presents a collection of all known mutations inside human exons which affect splicing enhancers and silencers and cause changes in the alternative splicing pattern of the corresponding genes. Findings. An algorithm was developed to derive a Splicing Potential (SP) table from the ASMD information. This table characterizes the influence of each oligonucleotide on the splicing effectiveness of the exon containing it. If the SP value for an oligonucleotide is positive, it promotes exon retention, while negative SP values mean the sequence favors exon skipping. The merit of the SP approach is the ability to separate splicing signals from a wide range of sequence motifs enriched in exonic sequences that are attributed to protein-coding properties and/or translation efficiency. Due to its direct derivation from observed splice site selection, SP has an advantage over other computational approaches for predicting alternative splicing. Conclusion. We show that a vast majority of known exonic splicing enhancers have highly positive cumulative SP values, while known splicing silencers have core motifs with strongly negative cumulative SP values. Our approach allows for computation of the cumulative SP value of any sequence segment and, thus, gives researchers the ability to measure the possible contribution of any sequence to the pattern of splicing. © 2008 Bechtel et al;licensee BioMed Central Ltd.

关键词： Splice Enhancer Exonic Splice Enhancer Code Potential Constitutive Exon 14th Exon

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Unexpected failure rates for modular assembly of engineered zinc fingers (vol 5, pg 374, 2008)

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NATURE METHODS 2008年第6期5卷 575-575页

作者： Ramirez, Cherie L. Foley, Jonathan E. Wright, David A. Mueller-Lerch, Felix Rahman, Shamim H. Cornu, Tatjana I. Winfrey, Ronnie J. Sander, Jeffry D. Fu, Fengli Townsend, Jeffrey A. Cathomen, Toni Voytas, Daniel F. Joung, J. Keith These authors contributed equally to this work. These authors contributed equally to this work. Department of Genetics Development and Cell Biology Iowa State University 1035A Roy J. Carver Co-Lab Ames Iowa 50011 USA. Charité Medical School Institute of Virology Hindenburgdamm 27 D-12203 Berlin Germany. Charité Medical School Institute of Virology Hindenburgdamm 27 D-12203 Berlin Germany. Charité Medical School Institute of Virology Hindenburgdamm 27 D-12203 Berlin Germany. Department of Genetics Development and Cell Biology Iowa State University 1035A Roy J. Carver Co-Lab Ames Iowa 50011 USA. Interdepartmental Graduate Program in Bioinformatics and Computational Biology 2114 Molecular Biology Building Iowa State University Ames Iowa 50011 USA. Interdepartmental Graduate Program in Bioinformatics and Computational Biology 2114 Molecular Biology Building Iowa State University Ames Iowa 50011 USA. Department of Genetics Development and Cell Biology Iowa State University 1035A Roy J. Carver Co-Lab Ames Iowa 50011 USA. Charité Medical School Institute of Virology Hindenburgdamm 27 D-12203 Berlin Germany. Department of Genetics Development and Cell Biology Iowa State University 1035A Roy J. Carver Co-Lab Ames Iowa 50011 USA. Department of Pathology Harvard Medical School Boston Massachusetts 02115 USA.

A letter to the editor is presented in response to an article on zinc fingers in a previous issue.

关键词： LETTERS to the editor ZINC

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Adaptive response to methylation damage in Escherichia colistudied by transcriptome and proteome analyses

Adaptive response to methylation damage in Escherichia colis...

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13th International Biotechnology Symposium and Exhibition(第13届IUPAC国际生物工程会议)

作者： Jong Hwan Baek Nam Su Heo Mee-Jung Han Sang Yup Lee Metabolic and Biomolecular Engineering National Research Laboratory Department of Chemical (&) Biomolecular Engineering (BK21 Program) BioPracess Engineering Research Center Center for Systems and Synthetic Biotechnology and Institute for the BioCentury Republic of Korea Metabolic and Biomolecular Engineering National Research Laboratory Department of Chemical (&) Biomolecular Engineering (BK21 Program) BioPracess Engineering Research Center Center for Systems and Synthetic Biotechnology and Institute for the BioCentury Republic of Korea Department of Bio and Brain Engineering and Bioinformatics Research Center KAIST 335 Gwahangno Yuseong-gu Daejeon 305-701 Republic of Korea

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Research Resource: Rapid Recruitment of Temporally Distinct Vascular Gene Sets by Estrogen

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Molecular Endocrinology 2008年第11期22卷 2544-2556页

作者： Schnoes, Katrin K. Jaffe, Iris Z. Iyer, Lakshmanan Dabreo, Alexandra Aronovitz, Mark Newfell, Brenna Hansen, Ulla Rosano, Giuseppe Mendelsohn, Michael E. Molecular Cardiology Research Institute (K.K.S. I.Z.J. L.I. A.D. M.A. B.N. M.E.M.) Tufts Medical Center Boston Massachusetts 02111 Department of Biology (U.H.) Program in Bioinformatics Boston University Boston Massachusetts 02215 Instituto di Ricovero e Cura a Carattere Scientifico (G.R.) San Raffaele Pisana 00163 Rome Italy

Cardiovascular disease is the leading cause of mortality for both men and women in developed countries. The sex steroid hormone estrogen is required for normal vascular physiology. Estrogen functions by binding to intracellular estrogen receptors (ER), ERα and ERβ, ligand-activated transcription factors that are expressed in both vascular endothelial and smooth muscle cells. We recently demonstrated that long-term (8 d) estrogen treatmentin vivoin mice recruits distinct vascular gene sets mediated by ERα and ERβ and that the promoters from these gene sets are enriched for binding sites of specific transcription factors, leading to the hypothesis that estrogen initiates a cascade of early transcriptional events that modulate gene expression in the vasculature. Here we test this hypothesis using gene expression profiling to examine initial transcriptional events (2–8 h) mediated by estrogen in blood vessels. Our data reveal that 1) estrogen regulates temporally distinct cascades of vascular gene expression, 2) initially, estrogen-mediated vascular gene repression predominates, 3) the earliest estrogen-recruited gene program is enriched in vascular transcription factors that can interact with binding sites present in estrogen-regulated vascular genes recruited subsequently, and 4) estrogen-regulated genes recruited next have specific functions, including lipid metabolism and cellular growth and proliferation that are potentially important for estrogen’s known vascular functions. In summary, estrogen directly and rapidly recruits specific transcriptional factors that then propagate distinct cascades of gene expression. These data define the temporal recruitment of specific vascular genes by estrogen and enable further analysis of the mechanisms by which estrogen directly regulates vascular function.

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The Genome Sequence of Taurine Cattle: A Window to Ruminant Biology and Evolution

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SCIENCE 2009年第5926期324卷 522-528页

作者： Elsik, Christine G. Tellam, Ross L. Worley, Kim C. Gibbs, Richard A. Abatepaulo, Antonio R. R. Abbey, Colette A. Adelson, David L. Aerts, Jan Ahola, Virpi Alexander, Lee Alioto, Tyler Almeida, Iassudara G. Amadio, Ariel F. Anatriello, Elen Antonarakis, Stylianos E. Anzola, Juan M. Astashyn, Alex Bahadue, Suria M. Baldwin, Cynthia L. Barris, Wes Baxter, Rebecca Bell, Stephanie Nicole Bennett, Anna K. Bennett, Gary L. Biase, Fernando H. Boldt, Clayton R. Bradley, Daniel G. Brinkman, Fiona S. L. Brinkmeyer-Langford, Candice L. Brown, Wendy C. Brownstein, Michael J. Buhay, Christian Caetano, Alexandre R. Camara, Francisco Carroll, Jeffrey A. Carvalho, Wanessa A. Casey, Theresa Cervelatti, Elaine P. Chack, Joseph Chacko, Elsa Chandrabose, Mimi M. Chapin, Jennifer E. Chapple, Charles E. Chen, Hsiu-Chuan Chen, Lin Cheng, Ye Cheng, Ze Childers, Christopher P. Chitko-McKown, Carol G. Chiu, Readman Choi, Jungwoo Chrast, Jacqueline Colley, Adam J. Connelley, Tomothy Cree, Andy Curry, Stacey Dalrymple, Brian Diep Dao, Marvin Davis, Clay de Oliveira, Carlo J. F. de Miranda Santos, Isabel K. F. de Campos, Tatiana A. Deobald, Heather Devinoy, Eve Dickins, C. Michael Yan, Ding Dinh, Huyen H. De Donato, Marcos Donohue, Kaitlin E. Donthu, Ravikiran Dovc, Peter Dugan-Rocha, Shannon Durbin, K. James Eberlein, Annett Edgar, Robert C. Egan, Amy Eggen, Andre Eichler, Evan E. Elhaik, Eran Ellis, Shirley A. Elnitski, Laura Ermolaeva, Olga Eyras, Eduardo Fitzsimmons, Carolyn J. Fowler, Gerald R. Franzin, Alessandra M. Fritz, Krista Gabisi, Ramatu Ayiesha Garcia, Gustavo R. Garcia, Jose Fernando Genini, Sem Gerlach, Daniel German, J. Bruce Gilbert, James G. R. Gill, Clare A. Gladney, Cody J. Glass, Elizabeth J. Goodell, Jason Grant, Jason R. Graur, Dan Greaser, Marion L. Green, Jonathan A. Green, Ronnie D. Guan, Leluo Guigo, Roderic Hadsell, Darryl L. Hagen, Darren E. Hakimov, Hatam A. Halgren, Rob Hamernik, Debora L. Hamilton, Cerissa Harhay, Gregory P. Harrow, Jennifer L. Hart, Elizabeth A. Hastings, Nicola Havlak, Paul Henrichsen, Charl Georgetown Univ Dept Biol 406 Reiss37th & O St NW Washington DC 20057 USA CSIRO Livestock Ind St Lucia Qld 4067 Australia Baylor Coll Med Dept Mol & Human Genet Human Genome Sequencing Ctr Houston TX 77030 USA Washington Univ Sch Med Genome Ctr St Louis MO 63108 USA Texas A&M Univ Dept Anim Sci College Stn TX 77843 USA Univ Adelaide Sch Mol Biomed & Sci Sch Agr Food & Wine Adelaide SA 5005 Australia Univ Washington Dept Genome Sci Seattle WA 98195 USA Howard Hughes Med Inst Seattle WA 98195 USA Natl Human Genome Res Inst Natl Inst Hlth Rockville MD 20878 USA Univ Pompeu Fabra Ctr Genomic Regulation Grp Recerca Informatica Biomed Inst Municipal Invest Med E-08003 Barcelona Spain USDA Cooperative State Res Educ & Extension Serv Washington DC 20250 USA USDA Agr Res Serv Natl Program Staff Beltsville MD 20705 USA Univ Illinois Urban Champaign Dept Anim Sci Urbana IL 61801 USA Univ Illinois Urban Champaign Inst Genomic Biol Urbana IL 61801 USA Simon Fraser Univ Dept Mol Biol Biochem Burnaby BC V5A 1S6 Canada Univ Sydney Fac Vet Sci Sydney NSW 2006 Australia Univ Lausanne Ctr Integrative Genomics CH-1015 Lausanne Switzerland Baylor Coll Med Dept Pediat Nutr USDA Agr Res Serv Childrens Nutr Res Ctr Houston TX 77030 USA Texas A&M Univ Dept Vet Integrative Biosci College Stn TX 77843 USA Univ Geneva Med Sch Dept Genetic Med & Dev CH-1211 Geneva Switzerland Swiss Inst Bioinformatics CH-1211 Geneva Switzerland Imperial Coll S Kensington Campus Div Mol Biosci London SW7 2AZ England Texas A&M Univ Dept Vet Pathobiol College Stn TX 77843 USA Natl Inst Hlth Natl Lib Med Natl Ctr Biotech Information Bethesda MD 20892 USA Wellcome Trust Sanger Inst Hinxton Informatics Dept Cambridge CB10 1HH England Univ London Royal Holloway Egham Dept Comp Sci Surrey TW20 0EX England Univ Houston Dept Biol & Biochem Houston TX 77204 USA Johns Hopkins Univ Sch Med McKusick Nathans Inst Genetic Med Baltimore MD 21205 USA 45 Monterey Dr Tiburon CA 94

To understand the biology and evolution of ruminants, the cattle genome was sequenced to about sevenfold coverage. The cattle genome contains a minimum of 22,000 genes, with a core set of 14,345 orthologs shared among seven mammalian species of which 1217 are absent or undetected in noneutherian (marsupial or monotreme) genomes. Cattle-specific evolutionary breakpoint regions in chromosomes have a higher density of segmental duplications, enrichment of repetitive elements, and species-specific variations in genes associated with lactation and immune responsiveness. Genes involved in metabolism are generally highly conserved, although five metabolic genes are deleted or extensively diverged from their human orthologs. The cattle genome sequence thus provides a resource for understanding mammalian evolution and accelerating livestock genetic improvement for milk and meat production.

关键词： Alternative Splicing Animals Animals, Domestic Biological Evolution Cattle Evolution, Molecular Evolution, Molecular Female Genetic Variation Genome Humans Male MicroRNAs/genetics MicroRNAs/genetics Molecular Sequence Data Proteins/genetics Sequence Analysis, DNA Species Specificity Synteny

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How to build a system that manages bioinformatics content

How to build a system that manages bioinformatics content

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2007 International Conference on Enterprise Information Systems and Web Technologies, EISWT 2007

作者： Phan, Vinhthuy Thomas, Allen Department of Computer Science Bioinformatics Program University of Memphis TN 38152 United States

ISBN: (纸本)9781615677245

We discuss how to build systems with sophisticated features based on a core set of bioinformatics tools. Beside from being the front-end server to the core analyses, such a system can manage users, bioinformatics content and shared data. Using tools available in the open-source community, we show how to build a system with such sophisticated features with a relatively minimal effort, especially in comparison to building such a system from scratch. We discuss the notion of Model-Content Management-View, under whose framework similar applications with such desirable features beyond the field bioinformatics can be built. Our system can be viewed at http://***/rnamotif.

关键词： bioinformatics

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Pursuit-evasion Voronoi diagrams in 1

Pursuit-evasion Voronoi diagrams in 1

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4th International Symposium on Voronoi Diagrams in Science and Engineering 2007, ISVD 2007

作者： Cheung, Warren Evans, William Department of Computer Science University of British Columbia University of British Columbia Bioinformatics Program

ISBN: (纸本)0769528694

We are given m pursuers and one evader. Each pursuer and the evader has an associated starting point in the plane, a maximum speed, and a start time. We also have a set of line segment obstacles with a total of n endpoints. Our task is to find those points in the plane, called the evader's region, that the evader can reach via evasive paths. A path is evasive if the evader can traverse the path from its starting point without encountering a pursuer along the way. The evader and the pursuers must obey their start time and speed constraints, and cannot go through obstacles. The partition of the plane into the evader's region and the remaining pursuers' region is called the pursuit-evasion Voronoi diagram. We study pursuit-evasion Voronoi diagrams for the 1 metric. We show that the complexity of the diagram is O((n + m)2(mn + m)) and that it can be calculated in polynomial time. © 2007 IEEE.

关键词： Graphic methods

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Comparative proteomic analysis of four biotechnologically important Escherichia coli strains for rational host strainselec tion

Comparative proteomic analysis of four biotechnologically im...

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13th International Biotechnology Symposium and Exhibition(第13届IUPAC国际生物工程会议)

作者： Xiao-Xia Xia Sang Yup Lee Department of Bio and Brain Engineering and Bioinformatics Research Center KAIST Daejeon Republic of Korea Metabolic and Biomolecular Engineering National Research Laboratory Department af Chemical and Biomolecular Engineering (BK21 Program) and BioProcess Engineering Research Center Center for Sys tems and Synthetic Biotechnology and Institute for the BioCenturyKAIST 335 Gwahangno Yuseong-gu Daejeon 305-701 Republic of Korea Metabolic and Biomolecular Engineering National Research Laboratory Department af Chemical and Biomolecular Engineering (BK21 Program) and BioProcess Engineering Research Center Center for Sys tems and Synthetic Biotechnology and Institute for the BioCenturyKAIST 335 Gwahangno Yuseong-gu Daejeon 305-701 Republic of Korea

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A systematic proteome-based approach for high-level extracellular production of recombinant proteins in Escherichia coli

A systematic proteome-based approach for high-level extracel...

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13th International Biotechnology Symposium and Exhibition(第13届IUPAC国际生物工程会议)

作者： Zhi-Gang Qian Xiao-Xia Xia Jong Hyun Choi Sang Yup Lee Department of Bio and Brain Engineering and Bioinformatics Research Center KAIST Daejeon Republic of Korea Metabolic and Biomolecular Engineering National Research Labora tory Department of Chemical and Biomolecular Engineering (BK21 Program) and BioProcess Engineering Research Center Center for Systems and Synthetic Biotechnology and Institute for the BioCenturyKAIST 335 Gwahangno Yuseong-gu Daejeon 305-701 Republic of Korea Metabolic and Biomolecular Engineering National Research Labora tory Department of Chemical and Biomolecular Engineering (BK21 Program) and BioProcess Engineering Research Center Center for Systems and Synthetic Biotechnology and Institute for the BioCenturyKAIST 335 Gwahangno Yuseong-gu Daejeon 305-701 Republic of Korea

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