Communication among CCDScollaborating groups ongoingactivity resolvedifferences identifyrefinements between CCDS update cycles. 欧洲生物信息研究所(EBI),美国国家生物技术信息中心(ncbi),韦尔科 姆基金会桑格研究所(WTSI)和加州大学圣克鲁斯分校(UCSC)。 CCDS CCDSDatabase CCDSset calculatedfollowing coordinated whole genome annotation updates carried out Ensembl.Annotation updates represent genes manualcuration automatedcomputational processing. 依据NCBI和Ensembl分别通过自动计算机处理加 上人工校正所作出的基因组注释更新, CCDSset includes coding regions full-length initiatingATG validstop-codon), can translatedfrom genomewithout frameshifts, useconsensus splice-sites. qualitytests performed may includesanalysis identifyputative pseudogenes, retrotransposed genes, consensus splice sites, supporting transcripts, proteinhomology. CCDS CCDSDatabase generalprocess flow CCDSgene set includes: 主要流程 comparegenome annotation results 比较NCBI和Ensembl分别作出的基 因组注释结果 identifyannotated coding regions haveidentical ocation coordinates genome找到有一致位点的编码区 qualityevaluation 质量评估 removelower quality CDSs from coreset pending additional review among collaborationgroups. 剔除其中还 有待合作小组之间进一步商榷的低质量CDS CCDS CCDSDatabase CCDS的特点每个基因都有唯一的标识+版本号 Annotated genes CCDSset uniqueidentifier number versionnumber (e.g., CCDS1.1, CCDS234.1). versionnumber CDSstructure changes, underlyinggenome sequence changes sequencebased genome browser update cycles, CCDSset mappedforward, maintaining identifiers. All changes existingCCDS genes collaborationagreement; singlegroup setunilaterally. 如果CDS结构改变或基因组序列改变则更新版本号 CCDS CCDSDatabase Vega project 脊椎动物基因组注释数据库(人工注释) VertebrateGenome Annotation (VEGA) database centralrepository highquality manual annotation vertebratefinished genome sequence. Human, mouse beingcompletely annotated, whereas otherspecies specificgenomic regions particularbiological interest. HAVANAgroup WelcomeTrust Sanger Institute. Human Release 38 (Mar 2010) http://vega.sanger.ac.uk/index.html About HGNC(HUGO Gene Nomenclature Committee Responsibilities权力与职责 eachknown human gene we approve genename symbol(short- form abbreviation). All approved symbols HGNCdatabase. Each symbol weensure eachgene onlygiven one approved gene symbol. uniquesymbol eachgene so otherscan talk about them, alsofacilitates electronic data retrieval from publications. preferenceeach symbol maintains parallel construction differentmembers genefamily canalso otherspecies, especially mouse.We have already approved over 28,000 symbols; vastmajority protein-codinggenes, alsoinclude symbols pseudogenes,non-coding RNAs, phenotypes genomicfeatures (see HGNC Search). (Human Genome Organization HUGO)HGNC ––人类基因组机构基因命名委员会 http://www.genenames.org/aboutHGNC.html Guidelines HumanGene Nomenclature 人类基因命名规则(符号加基因名) Humangene symbols upper-caseLatin letters upper-caseletters Arabicnumerals, C#orf#symbols. Symbols should representall known information about Symbolsshould spellwords matchabbreviations wouldcause problems databasesearching e.g. DNA. Ideally, symbols should longerthan six characters length.New symbols must duplicateexisting approved gene symbols human(HGNC database) mouse(MGD) databases presentedhere: Eachapproved gene symbol must short-formrepresentations descriptivegene name. Symbolsshould only contain Latin letters Arabicnumerals. Symbolsshould containpunctuation. Symbolsshould Symbolsdo containany reference human.Examples: BBS1 “Bardet-Biedl syndrome IDDM6"insulin-dependent diabetes mellitus Genenames Gene names should shouldconvey describeeverything known about firstletter symbolshould facilitatealphabetical listing grouping.Gene names writtenusing American spelling. Tissue specificity molecularweight designations should haveonly limited use acrossspecies prove inaccurate; however, genename absolutelynecessary. necessary,molecular weights may kilodaltonsusing SIunit: kDa spaceafter molecularweight. Gene names should includeterms nephew,cousin, sister etc. describefamilial relationships othergenes. Examples: AHDS “Allan-Herndon-Dudley syndrome”, ACO1 “aconitase soluble”,IDS "iduronate 2-sulfatase (Hunter syndrome)“, LFNG "lunatic fringe homolog (Drosophila)" Guidelines HumanGene Nomenclature 人类基因命名规则(符号+基因名) continue followinggene name syntax should Namesstart lowercase letter unless person´sname describing capitalisedabbreviation e.g. AHDS "Allan-Herndon-Dudley syndrome" ABCA1"ATP-binding cassette, sub-family (ABC1),member Descriptivemodifiers should follow mainpart name,separated commase.g. ACO1 "aconitase completealternative name beingincluded parenthesese.g. IDS "iduronate 2-sulfatase (Hunter syndrome)". otherspecies must ende.g. LFNG "lunatic fringe homolog (Drosophila)" ANLN"anillin, actin binding protein (scraps homolog, Drosophila)". Guidelines HumanGene Nomenclature 人类基因命名规则(符号加基因名) continue HGNCdatabase: eachknown human gene approve genename symbol(short-form abbreviation) publiccopy lastupdated Sunday March 21 22:12:19 2010 now28928 approved gene symbols, which19360 protein-codinggenes http://www.genenames.org/cgi-bin/hgnc_search.pl http://www.genenames.org/cgi-bin/hgnc_stats.pl Bruford EA, Lush MJ, Wright MW, Sneddon TP, Povey HGNCDatabase humangenome.. Nucleic Acids Res. 2008 Jan;36(Database issue):D445-8. PMID: 17984084 PDF followingformat: HGNC Database, HUGO Gene Nomenclature Committee (HGNC), EMBL Outstation Hinxton,European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SD, UK. (http://www.genenames.org/). 在网页http://www.genenames.org/cgi-bin/hgnc_search.pl上查询AHDS (AHDS “Allan-Herndon-Dudley syndrome”) 艾伦赫恩登-达德利综合征 HGNCdatabase: eachknown human gene approve genename symbol(short-form abbreviation) Ensembl Project: annotation billionbase pairs sequence(genebuild) EnsemblProject Ensemblproject 1999,some years before drafthuman genome completed.Even earlystage manualannotation billionbase pairs sequencewould offerresearchers timely access latestdata. automaticallyannotate genome,integrate otheravailable biological data makeall publiclyavailable via web.Since website´slaunch July2000, many more genomes have been added availabledata has also expanded includecomparative genomics, variation regulatorydata. Ensembl jointproject between European Bioinformatics Institute (EBI), EuropeanMolecular Biology Laboratory (EMBL), WellcomeTrust Sanger Institute (WTSI). Both institutes WellcomeTrust Genome Campus Hinxton,south Cambridge,United Kingdom. EnsemblAnnotation Process Ensembl Gene Set Maingenebuild (主要基因来源) Genes annotatedusing automatedpipeline genebuildprocedure. publicscientific databases. Transcripts from reviewed,manually curated set from Vegaproject, along reviewedprotein coding transcripts from CCDSproject. Moregenes (其它基因) Ensembl also includes automatically-annotated Ig segments non-codingRNAs. http://www.ensembl.org/info/docs/genebuild/index.html EnsemblAnnotation Process Ensembl Gene Set Annotationmethods 注释方法 pairwisesequence comparison, used Ensemblgenebuild alignmRNA generictool allows many alignment models used,either using exhaustive dynamic programming Wise2,also used genebuild,focuses biopolymers,commonly DNA proteinsequence. Algorithms packageinclude genewise Low-coveragegenomes annotatedusing modifiedpipeline which attempts locategenes across multiple scaffolds. IntroductionGene annotation provided Ensemblincludes both automatic annotation, i.e. genome-wide determination manualcuration, i.e. reviewed determination case-by-casebasis caselimited somespecies mouse).Furthermore, Ensembl imports annotation from FlyBase, WormBase SGD.Ensembl transcripts displayed ourwebsite Ensemblautomatic pipeline, termed Ensemblgenebuild. All Ensembl transcripts experimentalevidence automatedpipeline relies proteinsequences deposited publicdatabases from scientificcommunity. Manually-curated transcripts produced HAVANAgroup WelcomeTrust Sanger Institute separatetrack ourwebsite. EnsemblAnnotation Process Ensembl Gene Set Introduction(continnue) Ensemblgene uniqueENSG... ID) includes any spliced transcripts (ENST...) overlappingcoding sequence. Transcripts from Ensemblgenebuild (see below), Havana/Vegaset ConsensusCoding Sequence (CCDS) set may all samegene. Transcripts samegene ID may differ spliceevents, exons, cangive rise verydifferent proteins. isoforms,arising from alternative splicing. Transcript clusters overlappingcoding sequence separategenes. Two transcripts may overlap non-codingsequence (ie. intronic sequence UnTranslatedRegion (UTR), classifiedunder two separate genes. After Ensemblgene transcriptsequences transcriptnames (see below) EnsemblAnnotation Process Ensembl Gene Set GenebuildStandard Ensembl genebuilds high-coveragegenomes usuallytake leastfour months complete.While genebuildprocess eachspecies according mainsteps followed standardgenebuild everyspecies. EnsemblAnnotation Process Ensembl Gene Set Genebuild(continue) initialset-up genebuildinvolves loading Ensemblschema datababase runningseveral analyses across genomeincluding masking abinitio gene predictions. abinitio gene predictions websitedisplay purposes only supportingevidence genestructures displayed ourwebsite. EnsemblAnnotation Process Ensembl Gene Set Genebuild(continue) firststage Targettedstage. Here, species-specific proteins transcriptstructure EnsemblAnnotation Process Ensembl Gene Set Genebuild(continue) Targettedstage Similaritystage whichproteins from closely related species