Only Slight Impact of Predicted Replicative Capacity for Therapy Response Prediction 英文参考文献.docVIP

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Only Slight Impact of Predicted Replicative Capacity for Therapy Response Prediction 英文参考文献.doc

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Only Slight Impact of Predicted Replicative Capacity for Therapy Response Prediction 英文参考文献

OnlySlightImpactofPredictedReplicativeCapacityfor TherapyResponsePrediction HendrikWeisser1,Andre′ Altmann1*,SaletaSierra2,FrancescaIncardona3,DanielStruck4 ,Anders So¨nnerborg5,RolfKaiser2,MaurizioZazzi6,MonikaTschochner7,HaukeWalter7,ThomasLengauer1 1ComputationalBiologyandAppliedAlgorithmics,MaxPlanckInstituteforInformatics,Saarbru¨cken,Germany,2InstituteofVirology,UniversityofCologne,Cologne, Germany,3Informas.r.l.,Rome,Italy,4RetrovirologyLaboratory,CRP-Sante′, Strassen,Luxembourg,5DepartmentofMedicine,DivisionofInfectiousDiseases,Karolinska Institute,Stockholm,Sweden,6DepartmentofMolecularBiology,UniversityofSiena,Siena,Italy,7InstituteofClinicalandMolecularVirology,UniversityofErlangen, Erlangen,Germany Abstract Background:Replicationcapacity(RC)ofspecificHIVisolatesisoccasionallyblamedforunexpectedtreatmentresponses. However,theroleofviralRCinresponsetoantiretroviraltherapyisnotyetfullyunderstood. MaterialsandMethods:WedevelopedamethodforpredictingRCfromgenotypeusingsupportvectormachines(SVMs) trainedonabout300genotype-RCpairs.Next,westudiedtheimpactofpredictedviralRC(pRC)onthechangeofviralload (VL)andCD4 T-cellcount(CD4)duringthecourseoftherapyonabout3,000treatmentchangeepisodes(TCEs)extracted + fromtheEuResistintegrateddatabase.Specifically,linearregressionmodelsusingeithertreatmentactivityscores(TAS),the drug combination, or pRC or any combination of these covariates were trained to predict change in VL and CD4, respectively. Results:TheSVMmodelsachievedaSpearmancorrelation(r)of0.54betweenmeasuredRCandpRC.Thepredictionof changeinVL(CD4)wasbestat180(360)days,reachingacorrelationofr=0.45(r=0.27).Ingeneral,pRCwasinversely correlated to drug resistance at treatment start (on average r=20.38). Inclusion of pRC in the linear regression models significantlyimprovedpredictionofvirologicalresponsetotreatmentbasedeitheronthedrugcombinationorontheTAS (t-test;p-valuesrangefrom0.0247to41026)butnotforthemodelusingbothTASanddrugcombination.Forpredicting thechange