Can Survival Prediction Be Improved By Merging Gene Expression Data Sets 英文参考文献.docVIP

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Can Survival Prediction Be Improved By Merging Gene Expression Data Sets 英文参考文献.doc

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Can Survival Prediction Be Improved By Merging Gene Expression Data Sets 英文参考文献

CanSurvivalPredictionBeImprovedByMergingGene ExpressionDataSets? HalehYasrebi1,2*,PeterSperisen2,VivianePraz2,PhilippBucher1,2 1SwissInstituteforExperimentalCancerResearch(ISREC),SwissFederalInstituteofTechnology(EPFL),SchoolofLifeSciences,EPFLSVISREC,Lausanne,Switzerland, 2SwissInstituteofBioinformatics,EPFLSVISREC,Lausanne,Switzerland Abstract Background:High-throughputgeneexpressionprofilingtechnologiesgeneratingawealthofdata,areincreasinglyusedfor characterizationoftumorbiopsiesforclinicaltrials.Byapplyingmachinelearningalgorithmstosuchclinicallydocumented data sets, one hopes to improve tumor diagnosis, prognosis, as well as prediction of treatment response. However, the limitednumberofpatientsenrolledinasingletrialstudylimitsthepowerofmachinelearningapproachesduetoover- fitting.Onecouldpartially overcomethislimitation bymergingdatafrom differentstudies.Nevertheless,suchdatasets differfromeachotherwithregardtotechnicalbiases,patientselectioncriteriaandfollow-uptreatment.Itisthereforenot clearatallwhethertheadvantageofincreasedsamplesizeoutweighsthedisadvantageofhigherheterogeneityofmerged data sets. Here, we present a systematic study to answer this question specifically for breast cancer data sets. We use survivalpredictionbasedonCoxregressionasanassaytomeasuretheaddedvalueofmergeddatasets. Results: Using time-dependent Receiver Operating Characteristic-Area Under the Curve (ROC-AUC) and hazard ratio as performancemeasures,weseeinoverallnosignificantimprovementordeteriorationofsurvivalpredictionwithmerged datasetsascomparedtoindividualdatasets.Thisapparentlywasduetothefactthatafewgeneswithstrongprognostic powerwerenotavailableonallmicroarrayplatformsandthuswerenotretainedinthemergeddatasets.Surprisingly,we foundthattheoverallbestperformancewasachievedwithasingle-genepredictorconsistingofCYB5D1. Conclusions:Mergingdidnotdeteriorateperformanceonaveragedespite(a)Thediversityofmicroarrayplatformsused. (b)Theheterogeneityofpatientscohorts.(c)Theheterogeneityof