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1、GappedBLASTandPSI-BLAST:anewgenerationofproteindatabasesearchprogramsStephenF.Altschul*,ThomasL.Madden,AlejandroA.Schäffer1,JinghuiZhang,ZhengZhang2,WebbMiller2andDavidJ.LipmanNationalCenterforBiotechnologyInformation,NationalLibraryofMedicine,NationalInstitutesofHealth,Bethe
2、sda,MD20894,USA,1LaboratoryofGeneticDiseaseResearch,NationalHumanGenomeResearchInstitute,NationalInstitutesofHealth,Bethesda,MD20892,USAand2DepartmentofComputerScienceandEngineering,PennsylvaniaStateUniversity,UniversityPark,PA16802,USAReceivedJune20,1997;RevisedandAcceptedJu
3、ly16,1997ABSTRACTTheBLASTprogramsarewidelyusedtoolsforsearchingproteinandDNAdatabasesforsequencesimilarities.Forproteincomparisons,avarietyofdefinitional,algorithmicandstatisticalrefinementsdescribedherepermitstheexecutiontimeoftheBLASTprogramstobedecreasedsubstantiallywhilee
4、nhancingtheirsensitivitytoweaksimilarities.Anewcriterionfortriggeringtheextensionofwordhits,combinedwithanewheuristicforgeneratinggappedalignments,yieldsagappedBLASTprogramthatrunsatapproximatelythreetimesthespeedoftheoriginal.Inaddition,amethodisintroducedforautomaticallycom
5、biningstatisticallysignificantalignmentsproducedbyBLASTintoaposition-specificscorematrix,andsearchingthedatabaseusingthismatrix.TheresultingPosition-SpecificIteratedBLAST(PSI-BLAST)programrunsatapproximatelythesamespeedperiterationasgappedBLAST,butinmanycasesismuchmoresensiti
6、vetoweakbutbiologicallyrelevantsequencesimilarities.PSI-BLASTisusedtouncoverseveralnewandinterestingmembersoftheBRCTsuperfamily.INTRODUCTIONVariationsoftheBLASTalgorithm(1)havebeenincorporatedintoseveralpopularprogramsforsearchingproteinandDNAdatabasesforsequencesimilarities.
7、BLASTprogramshavebeenwrittentocompareproteinorDNAquerieswithproteinorDNAdatabasesinanycombination,withDNAsequencesoftenundergoingconceptualtranslationbeforeanycomparisonisperformed.Wewillusetheblastpprogram,whichcomparesproteinqueriestoproteindatabases,asaprototypeforBLAST,al
8、thoughtheideaspresentedextendimmediatelytootherversionsthatinvolveth
