A General Definition and Nomenclature for Alternative Splicing Events 英文参考文献.docVIP

AGeneralDefinitionandNomenclatureforAlternative SplicingEvents MichaelSammeth.*,SylvainFoissac.,RodericGuigo′ CentredeRegulacio′ Geno`mica,Barcelona,Spain Abstract Understandingthemolecularmechanismsresponsiblefortheregulationofthetranscriptomepresentineukaryoticcellsis one ofthe mostchallengingtasks in thepostgenomic era. Inthis regard, alternative splicing (AS)is a key phenomenon contributing to the production of different mature transcripts from the same primary RNA sequence. As a plethora of different transcript forms is available in databases, a first step to uncover the biology that drives AS is to identify the different types of reflected splicing variation. In this work, we present ageneral definition of theAS eventalong with a notationsystemthatinvolvestherelativepositionsofthesplicesites.Thisnomenclatureunivocallyanddynamicallyassigns aspecific‘‘AScode’’toeverypossiblepatternofsplicingvariation.Onthebasisofthisdefinitionandthecorresponding codes,wehavedevelopedacomputationaltool(AStalavista)thatautomaticallycharacterizesthecompletelandscapeofAS eventsinagiventranscriptannotationofagenome,thusprovidingaplatformtoinvestigatethetranscriptomediversity acrossgenes,chromosomes,andspecies.Ouranalysisrevealsthatasubstantialpart—inhumanmorethanaquarter—of theobservedsplicingvariationsareignoredincommonclassificationpipelines.WehaveusedAStalavistatoinvestigateand tocomparetheASlandscapeofdifferentreferenceannotationsetsinhumanandinothermetazoanspeciesandfoundthat proportions of AS events change substantially depending on the annotation protocol, species-specific attributes, and coding constraints acting on the transcripts. The AStalavista system therefore provides a general framework to conduct specificstudiesinvestigatingtheoccurrence,impact,andregulationofAS. Citation: Sammeth M, Foissac S, Guigo′ R (2008) A General Definition and Nomenclature for Alternative Splicing Events. PLoS Comput Biol 4(8): e1000147. doi:10.1371/journal.pcbi.1000147 Editor:MichaelR.Bre