Bayesian Mixture Models for Assessment of Gene Differential Behaviour and Prediction of pCR through the Integration of Copy Number and Gene Expression Data.docVIP

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Bayesian Mixture Models for Assessment of Gene Differential Behaviour and Prediction of pCR through the Integration of Copy Number and Gene Expression Data.doc

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Bayesian Mixture Models for Assessment of Gene Differential Behaviour and Prediction of pCR through the Integration of Copy Number and Gene Expression Data

BayesianMixtureModelsforAssessmentofGene DifferentialBehaviourandPredictionofpCRthroughthe IntegrationofCopyNumberandGeneExpressionData FilippoTrentini1,YuanJi2*,TakayukiIwamoto3,YuanQi4,LajosPusztai5,PeterMu¨ller6 1University Centre of Statistics in the Biomedical Sciences, Vita-Salute San Raffaele University, Milan, Italy, 2Center for Clinical and Research Informatics, NorthShore University HealthSystem, Evanston, Illinois, United States of America, 3Department of Breast and Endocrine Surgery, Okayama University Hospital, Okayama, Japan, 4DivisionofQuantitativeSciences,MDAndersonCancerCenter,Houston,Texas,UnitedStatesofAmerica,5ChiefofBreastMedicalOncology,YaleSchoolofMedicine, NewHaven,Connecticut,UnitedStatesofAmerica,6DepartmentofMathematics,UniversityofTexas,Austin,Texas,UnitedStatesofAmerica Abstract WeconsidermodelingjointlymicroarrayRNAexpressionandDNAcopynumberdata.WeproposeBayesianmixturemodels thatdefinelatentGaussianprobitscoresfortheDNAandRNA,andintegratebetweenthetwoplatformsviaaregressionof the RNA probit scores on the DNA probit scores. Such a regression conveniently allows us to include additional sample specificcovariatessuchasbiologicalconditionsandclinicaloutcomes.Thetwodevelopedmethodsareaimedrespectively tomakeinferenceondifferentialbehaviourofgenesinpatientsshowingdifferentsubtypesofbreastcancerandtopredict thepathologicalcompleteresponse(pCR)ofpatientsborrowingstrengthacrossthegenomicplatforms.Posteriorinference iscarriedoutviaMCMCsimulations.Wedemonstratetheproposedmethodologyusingapublisheddatasetconsistingof 121breastcancerpatients. Citation:TrentiniF,JiY,IwamotoT,QiY,PusztaiL,etal.(2013)BayesianMixtureModelsforAssessmentofGeneDifferentialBehaviourandPredictionofpCR throughtheIntegrationofCopyNumberandGeneExpressionData.PLoSONE8(7):e68071.doi:10.1371/journal.pone.0068071 Editor:XiaofengWang,ClevelandClinicLernerResearchInstitute,UnitedStatesofAmerica ReceivedNovember15,2012;AcceptedMay23,2013;PublishedJuly12,2013 Copyright: ? 2013 Trentin