A Two-Stage Random Forest-Based Pathway Analysis Method 英文参考文献.docVIP

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A Two-Stage Random Forest-Based Pathway Analysis Method 英文参考文献.doc

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A Two-Stage Random Forest-Based Pathway Analysis Method 英文参考文献

ATwo-StageRandomForest-BasedPathwayAnalysis Method Ren-HuaChung1,2*,Ying-ErhChen3 1DivisionofBiostatisticsandBioinformatics,InstituteofPopulationHealthSciences,NationalHealthResearchInstitutes,Zhunan,Miaoli,Taiwan,2CenterforGenetic EpidemiologyandStatisticalGenetics,JohnP.HussmanInstituteforHumanGenomics,UniversityofMiamiMillerSchoolofMedicine,Miami,Florida,UnitedStatesof America,3DepartmentofEconomics,NorthCarolinaStateUniversity,Raleigh,NorthCarolina,UnitedStatesofAmerica Abstract Pathway analysis provides a powerful approach for identifying the joint effect of genes grouped into biologically-based pathwaysondisease.Pathwayanalysisisalsoanattractiveapproachforasecondaryanalysisofgenome-wideassociation study (GWAS) data that may still yield new results from these valuable datasets. Most of the current pathway analysis methodsfocusedontestingthecumulativemaineffectsofgenesinapathway.However,forcomplexdiseases,gene-gene interactionsareexpectedtoplayacriticalroleindiseaseetiology.Weextendedarandomforest-basedmethodforpathway analysisbyincorporatingatwo-stagedesign.WeusedsimulationstoverifythattheproposedmethodhasthecorrecttypeI error rates. We also used simulations to show that the method is more powerful than the original random forest-based pathway approach and the set-based test implemented in PLINK in the presence of gene-gene interactions. Finally, we applied the method to a breast cancer GWAS dataset and a lung cancer GWAS dataset and interesting pathways were identifiedthathaveimplicationsforbreastandlungcancers. Citation:ChungR-H,ChenY-E(2012)ATwo-StageRandomForest-BasedPathwayAnalysisMethod.PLoSONE7(5):e36662.doi:10.1371/journal.pone.0036662 Editor:Xi-NianZuo,InstituteofPsychology,ChineseAcademyofSciences,China ReceivedJuly14,2011;AcceptedApril9,2012;PublishedMay7,2012 Copyright: ? 2012 Chung, Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricteduse,distribution,andreproducti