Robust Detection and Genotyping of Single Feature Polymorphisms from Gene Expression Data 英文参考文献.docVIP

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Robust Detection and Genotyping of Single Feature Polymorphisms from Gene Expression Data 英文参考文献.doc

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Robust Detection and Genotyping of Single Feature Polymorphisms from Gene Expression Data 英文参考文献

RobustDetectionandGenotypingofSingleFeature PolymorphismsfromGeneExpressionData MinghuiWang1.,XiaohuaHu1.,GangLi1,LindseyJ.Leach2,ElenaPotokina2,ArnisDruka3 ,Robbie Waugh3,MichaelJ.Kearsey2,ZeweiLuo1,2* 1LaboratoryofPopulationQuantitativeGenetics,TheStateKeyLaboratoryofGeneticEngineering,InstituteofBiostatistics,SchoolofLifeSciences,FudanUniversity, Shanghai, China, 2School of Biosciences, The University of Birmingham, Edgbaston, Birmingham, United Kingdom, 3Scottish Crop Research Institute, Invergowrie, Dundee,UnitedKingdom Abstract ItiswellknownthatAffymetrixmicroarraysarewidelyusedtopredictgenome-widegeneexpressionandgenome-wide geneticpolymorphismsfromRNAandgenomicDNAhybridizationexperiments,respectively.Ithasrecentlybeenproposed to integrate the two predictions by use of RNA microarray data only. Although the ability to detect single feature polymorphisms(SFPs)fromRNAmicroarraydatahasmanypracticalimplicationsforgenomestudyinbothsequencedand unsequenced species, it raises enormous challenges for statistical modelling and analysis of microarray gene expression data for this objective. Several methods are proposed to predict SFPs from the gene expression profile. However, their performanceishighlyvulnerabletodifferentialexpressionofgenes.TheSFPsthuspredictedareeventuallyareflectionof differentially expressed genes rather than genuine sequence polymorphisms. To address the problem, we developed a novelstatisticalmethodtoseparatethebindingaffinitybetweenatranscriptanditstargetingprobeandtheparameter measuring transcript abundance from perfect-match hybridization values of Affymetrix gene expression data. We implementedaBayesianapproachtodetectSFPsandtogenotypeasegregatingpopulationatthedetectedSFPs.Basedon analysisofthreeAffymetrixmicroarraydatasets,wedemonstratedthatthepresentmethodconfersasignificantlyimproved robustnessandaccuracyindetectingtheSFPsthatcarrygenuinesequencepolymorphismswhencomparedtoitsrivalsin theliterature.Themethoddevelopedinthispaperwillprovi