Predictive Power Estimation Algorithm (PPEA) - A New Algorithm to Reduce Overfitting for Genomic Biomarker Discovery 英文参考文献.docVIP

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Predictive Power Estimation Algorithm (PPEA) - A New Algorithm to Reduce Overfitting for Genomic Biomarker Discovery 英文参考文献.doc

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Predictive Power Estimation Algorithm (PPEA) - A New Algorithm to Reduce Overfitting for Genomic Biomarker Discovery 英文参考文献

PredictivePowerEstimationAlgorithm(PPEA)-ANew AlgorithmtoReduceOverfittingforGenomicBiomarker Discovery JiangangLiu1,3,4,RobertA.Jolly2,AaronT.Smith2,GeorgeH.Searfoss2,KeithM.Goldstein2,VladimirN. Uversky4,5,6,KeithDunker3,4,ShuyuLi1,CraigE.Thomas2*,TaoWei1* 1TranslationalScience,LillyResearchLaboratories,aDivisionofEliLillyCo.,Indianapolis,Indiana,UnitedStatesofAmerica,2Toxicology,LillyResearchLaboratories,a DivisionofEliLillyCo.,Indianapolis,Indiana,UnitedStatesofAmerica,3SchoolofInformatics,IndianaUniversity-PurdueUniversityIndianapolis,Indianapolis,Indiana, UnitedStatesofAmerica,4CenterforComputationalBiologyandBioinformatics,SchoolofMedicine,IndianaUniversity,Indianapolis,Indiana,UnitedStatesofAmerica, 5DepartmentofMolecularMedicine,UniversityofSouthFlorida,Tampa,Florida,UnitedStatesofAmerica,6InstituteforBiologicalInstrumentation,RussianAcademyof Sciences,Pushchino,MoscowRegion,Russia Abstract Toxicogenomicspromisestoaidinpredictingadverseeffects,understandingthemechanismsofdrugactionortoxicity,and uncoveringunexpectedorsecondarypharmacology.However,modelingadverseeffectsusinghighdimensionalandhigh noise genomic data is prone to over-fitting. Models constructed from such data sets often consist of alarge number of genes with no obvious functional relevance to the biological effect the model intends to predict that can make it challengingtointerpretthemodelingresults.Toaddresstheseissues,wedevelopedanovelalgorithm,PredictivePower EstimationAlgorithm(PPEA),whichestimatesthepredictivepowerofeachindividualtranscriptthroughaniterativetwo- waybootstrappingprocedure.Byrepeatedlyenforcingthatthesamplenumberislargerthanthetranscriptnumber,ineach iterationofmodelingandtesting,PPEAreducesthepotentialriskofoverfitting.Weshowwiththreedifferentcasesstudies that: (1) PPEA can quickly derive a reliable rank order of predictive power of individual transcripts in a relatively small numberofiterations,(2)thetoprankedtranscriptstendtobefunctionallyrelatedtothephenotypetheyarein