Estimating the Numbers of Malaria Infections in Blood Samples Using High-Resolution Genotyping Data 英文参考文献.docVIP

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Estimating the Numbers of Malaria Infections in Blood Samples Using High-Resolution Genotyping Data 英文参考文献.doc

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Estimating the Numbers of Malaria Infections in Blood Samples Using High-Resolution Genotyping Data 英文参考文献

EstimatingtheNumbersofMalariaInfectionsinBlood SamplesUsingHigh-ResolutionGenotypingData AmandaRoss1,2*,CristianKoepfli1,2,3,XiaohongLi4,SonjaSchoepflin1,2¤,PeterSiba5,IvoMueller3,5,6, IngridFelger1,2,ThomasSmith1,2 1SwissTropicalandPublicHealthInstitute,Basel,Switzerland,2UniversityofBasel,Basel,Switzerland,3InfectionandImmunityDivision,WalterandElizaHallInstitute, Parkville,Australia,4BGMedicineInc.,Waltham,Massachusetts,UnitedStatesofAmerica,5PapuaNewGuineaInstituteofMedicalResearch,Goroka,EasternHighlands Province,PapuaNewGuinea,6BarcelonaCentreforInternationalHealthResearch,Barcelona,Spain Abstract Peoplelivinginendemicareasoftenhabourseveralmalariainfectionsatonce.High-resolutiongenotypingcandistinguish betweeninfectionsbydetectingthepresenceofdifferentallelesatapolymorphiclocus.Howeverthenumberofinfections may not be accurately counted sinceparasites frommultiple infections may carry the sameallele. We usesimulation to determinethecircumstancesunderwhichthenumberofobservedgenotypesarelikelytobesubstantiallylessthanthe numberofinfectionspresentandinvestigatetheperformanceoftwomethodsforestimatingthenumbersofinfections fromhigh-resolutiongenotypingdata.Thesimulations suggestthattheproblemisnotsubstantialinmostdatasets: the disparitybetweenthemeannumbersofinfectionsandofobservedgenotypeswassmallwhentherewas20ormorealleles, 20ormorebloodsamples,ameannumberofinfectionsof6orlessandwherethefrequencyofthemostcommonallele wasnogreaterthan20%.Theissueofmultipleinfectionscarryingthesamealleleisunlikelytobeamajorcomponentofthe errors in PCR-based genotyping.Simulations also showed that, with heterogeneity in allele frequencies, the observed frequenciesarenotagoodapproximationofthetrueallelefrequencies.Thefirstmethodthatweproposedtoestimatethe numbersofinfectionsassumesthattheyareagoodapproximationandhencedidpoorlyinthepresenceofheterogeneity. In contrast, the second method by Li et al estimates both the numbers of infections and the true allele frequencies simul