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Evidence-ranked motif identification.doc

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Evidence-ranked motif identification

Georgievetal.GenomeBiology2010,11:R19 /2010/11/2/R19 METHOD OpenAccess Evidence-rankedmotifidentification StoyanGeorgiev1,2,AlanPBoyle1,2,KarthikJayasurya1,2,XuanDing2,SayanMukherjee2,3,4,5,UweOhler2,3,6* Abstract cERMITisacomputationallyefficientmotifdiscoverytoolbasedonanalyzinggenome-widequantitativeregulatory evidence.Insteadofpre-selectingpromisingcandidatesequences,itutilizesinformationacrossallsequence regionstosearchforhigh-scoringmotifs.WeapplycERMITonarangeofdirectbindingandoverexpressiondata- sets;itsubstantiallyoutperformsstate-of-the-artapproachesoncuratedChIP-chipdatasets,andeasilyscalestocur- rentmammalianChIP-seqexperimentswithdataonthousandsofnon-codingregions. Background extensively toaddress this goal bymeans ofiteratively Withthecontinuinggrowthandscale-upofgenomeand optimizingasuitableobjectivefunction[4-7].Theuseof transcriptomesequencingofalargenumberofeukaryotes, additional information, suchassequences fromrelated there has been increasing interest in gaining a better species (for example, [8]), orpriors onthe TFbinding understandingofthefunctionalconnectionsbetweenall domainornucleosomepositions[9,10],hasledtonotice- thegeneswithinacomplexorganism.Regulatoryfactors ableimprovements intheperformance ofthese strate- thatcontroltheactivationorrepressionofageneonthe gies.AsalternativestoPSSMs,motifscanbedescribedas transcriptionalorpost-transcriptionalleveloftenrecognize consensusstringsoveradegeneratealphabet.Thisrepre- specificDNAorRNAsequenceelements.Oneofthefirst sentationhasallowedfortheexhaustiveidentificationof stepstowardsunderstandingthefunctionalcharacteristics motifsthatareover-representedcomparedtoagenomic of regulators such as transcription factors (TFs) is to backgroundmodel[11-14],andfrequentlymakesuseof obtainaccuraterepresentationsoftheirpreferredbinding efficientdatastructuressuchassuffixarraystosearchfor sitesandthelocationoftheiroccurrences,whichcanthen overrepresented oligomers