Analyzing the Number of Common Integration Sites of Viral Vectors – New Methods and Computer Programs 英文参考文献.docVIP

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Analyzing the Number of Common Integration Sites of Viral Vectors – New Methods and Computer Programs 英文参考文献.doc

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Analyzing the Number of Common Integration Sites of Viral Vectors – New Methods and Computer Programs 英文参考文献

AnalyzingtheNumberofCommonIntegrationSitesof ViralVectors–NewMethodsandComputerPrograms UlrichAbel1,2*.,AnnetteDeichmann2.,AliNowrouzi2,RichardGabriel2,CynthiaC.Bartholomae2, HannoGlimm2,ChristofvonKalle2,ManfredSchmidt2* 1DepartmentofMedicalBiometry,UniversityofHeidelberg,Heidelberg,Germany,2DepartmentofTranslationalOncology,NationalCenterforTumorDiseases(NCT) andGermanCancerResearchCenter(DKFZ),Heidelberg,Germany Abstract Vectorsbasedonc-retrovirusesorlentiviruseshavebeenshowntostablyexpresstherapeuticaltransgenesandeffectively curedifferenthematologicaldiseases.Molecularfollowupoftheinsertionalrepertoireofgenecorrectedcellsinpatients and preclinical animal models revealed different integration preferences in the host genome including clusters of integrationsinsmallgenomicareas(CIS;commonintegrationssites).Inthemajority,theseCISwerefoundinorneargenes, withthepotentialtoinfluencetheclonalfateoftheaffectedcell.Todeterminewhethertheobserveddegreeofclustering isstatisticallycompatiblewithanassumedstandardmodelofspatialdistributionofintegrants,wehavedevelopedvarious methodsandcomputerprogramsforc-retroviralandlentiviralintegrationsitedistribution.Inparticular,wehavedevised andimplementedmathematicalandstatisticalapproachesforcomparingtwoexperimentalsampleswithdifferentnumbers ofintegrationsiteswithrespecttothepropensitytoformCISaswellasfortheanalysisofcoincidencesofintegrationsites obtainedfromdifferentbloodcompartments.Theprogramsandstatisticaltoolsdescribedhereareavailableasworkspaces inRcodeandallowthefastdetectionofexcessiveclusteringofintegrationsitesfromanyretrovirallytransducedsample andthuscontributetotheassessmentofpotentialtreatment-relatedrisksinpreclinicalandclinicalretroviralgenetherapy studies. Citation:AbelU,DeichmannA,NowrouziA,GabrielR,BartholomaeCC,etal.(2011)AnalyzingtheNumberofCommonIntegrationSitesofViralVectors–New MethodsandComputerPrograms.PLoSONE6(10):e24247.doi:10.1371/journal.pone.0024247 Editor:JohnA.Chiorini,NationalInstituteofDentalandCr