An Integrated Approach to Identifying Cis-Regulatory Modules in the Human Genome 英文参考文献.docVIP

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An Integrated Approach to Identifying Cis-Regulatory Modules in the Human Genome 英文参考文献.doc

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An Integrated Approach to Identifying Cis-Regulatory Modules in the Human Genome 英文参考文献

AnIntegratedApproachtoIdentifyingCis-Regulatory ModulesintheHumanGenome Kyoung-JaeWon1,SaurabhAgarwal2,LiShen1,RobertShoemaker1,BingRen2*,WeiWang1* 1DepartmentofChemistryandBiochemistry,UniversityofCaliforniaSanDiego,LaJolla,California,UnitedStatesofAmerica,2LudwigInstituteforCancerResearchand DepartmentofCellularandMolecularMedicine,UniversityofCaliforniaSanDiego,LaJolla,California,UnitedStatesofAmerica Abstract In eukaryotic genomes, it is challenging to accurately determine target sites of transcription factors (TFs) by only using sequenceinformation.PreviouseffortsweremadetotacklethistaskbyconsideringthefactthatTFbindingsitestendtobe moreconservedthanotherfunctionalsitesandthebindingsitesofseveralTFsareoftenclustered.Recently,ChIP-chipand ChIP-sequencing experiments have been accumulated to identify TF binding sites as well as survey the chromatin modification patterns at the regulatory elements such as promoters and enhancers. We propose here a hidden Markov model(HMM)toincorporatesequencemotifinformation,TF-DNAinteractiondataandchromatinmodificationpatternsto preciselyidentifycis-regulatorymodules(CRMs).WeconductedChIP-chipexperimentsonfourTFs,CREB,E2F1,MAX,and YY1in1%ofthehumangenome.WethentrainedahiddenMarkovmodel(HMM)toidentifythelabelsoftheCRMsby incorporatingthesequencemotifsrecognizedbytheseTFsandtheChIP-chipratio.Chromatinmodificationdatawasused topredictthefunctionalsitesandtofurtherremovefalsepositives.Cross-validationshowedthatourintegratedHMMhada performance superior to other existing methods on predicting CRMs. Incorporating histone signature information successfullypenalizedfalse predictionandimprovedthewholeperformance. Thedatasetweusedandthesoftwareare availableat/CIS/. Citation: Won K-J, Agarwal S, Shen L, Shoemaker R, Ren B, et al. (2008) An Integrated Approach to Identifying Cis-Regulatory Modules in the Human Genome.PLoSONE4(5):e5501.doi:10.1371/journal.pone.0005501 Editor:RayaKhanin,UniversityofGlasgow,UnitedKingdom ReceivedOctober2,20