HMMSplicer A Tool for Efficient and Sensitive Discovery of Known and Novel Splice Junctions in RNA-Seq Data 英文参考文献.docVIP

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HMMSplicer A Tool for Efficient and Sensitive Discovery of Known and Novel Splice Junctions in RNA-Seq Data 英文参考文献.doc

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HMMSplicer A Tool for Efficient and Sensitive Discovery of Known and Novel Splice Junctions in RNA-Seq Data 英文参考文献

HMMSplicer:AToolforEfficientandSensitiveDiscovery ofKnownandNovelSpliceJunctionsinRNA-SeqData MichelleT.Dimon1,2,KatherineSorber1,JosephL.DeRisi1,3* 1Department of Biochemistry and Biophysics, University of California San Francisco, San Francisco, California, United States of America, 2Biological and Medical InformaticsProgram,UniversityofCaliforniaSanFrancisco,SanFrancisco,California,UnitedStatesofAmerica,3HowardHughesMedicalInstitute,Bethesda,Maryland, UnitedStatesofAmerica Abstract Background: High-throughput sequencing of an organism’s transcriptome, or RNA-Seq, is a valuable and versatile new strategyforcapturingsnapshotsofgeneexpression.However,transcriptomesequencingcreatesanewclassofalignment problem:mappingshortreadsthatspanexon-exonjunctionsbacktothereferencegenome,especiallyinthecasewherea splicejunctionispreviouslyunknown. Methodology/Principal Findings: Here we introduce HMMSplicer, an accurate and efficient algorithm for discovering canonical and non-canonical splice junctions in short read datasets. HMMSplicer identifies more splice junctions than currentlyavailablealgorithmswhentestedonpubliclyavailableA.thaliana,P.falciparum,andH.sapiensdatasetswithouta reductioninspecificity. Conclusions/Significance:HMMSplicerwasfoundtoperformespeciallywellincompactgenomesandongeneswithlow expressionlevels,alternativespliceisoforms,ornon-canonicalsplicejunctions.BecauseHHMSplicerdoesnotrelyonpre- builtgenemodels,theproductsofinexactsplicingarealsodetected.ForH.sapiens,wefind3.6%of39splicesitesand1.4% of59splicesitesareinexact,typicallydifferingby3basesineitherdirection.Inaddition,HMMSplicerprovidesascorefor everypredictedjunctionallowingtheusertosetathresholdtotunefalsepositiveratesdependingontheneedsofthe experiment. HMMSplicer is implemented in Python. Code and documentation are freely available at http://derisilab.ucsf. edu/software/hmmsplicer. Citation: Dimon MT, Sorber K, DeRisi JL (2010) HMMSplicer: A Tool for Efficient and Sensitive Discovery of Known and