Needles in the Haystack Identifying Individuals Present in Pooled Genomic Data 英文参考文献.docVIP

NeedlesintheHaystack:IdentifyingIndividualsPresent inPooledGenomicData RosemaryBraun1*,WilliamRowe1,CarlSchaefer2,JinghuiZhang1,KennethBuetow1,2 1Laboratory of Population Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America, 2Center for Biomedical InformaticsandInformationTechnology,NationalCancerInstitute,NationalInstitutesofHealth,Bethesda,Maryland,UnitedStatesofAmerica Abstract Recentpublicationshavedescribedandappliedanovelmetricthatquantifiesthegeneticdistanceofanindividualwith respect to two population samples, and have suggested that the metric makes it possible to infer the presence of an individual of known genotype in a sample for which only the marginal allele frequencies are known. However, the assumptions,limitations,andutilityofthismetricremainedincompletelycharacterized.Herewepresentempiricaltestsof the method using publicly accessible genotypes, as well as analytical investigations of the method’s strengths and limitations. The results reveal that the null distribution is sensitive to the underlying assumptions, making it difficult to accuratelycalibratethresholdsforclassifyinganindividualasamemberofthepopulationsamples.Asaresult,thefalse- positive rates obtained in practice are considerably higher than previously believed. However, despite the metric’s inadequacies for identifying the presence of an individual in a sample, our results suggest potential avenues for future researchontuningthismethodtoproblemsofancestryinferenceordiseaseprediction.Byrevealingboththestrengthsand limitations of the proposed method, we hope to elucidate situations in which this distance metric may be used in an appropriatemanner.WealsodiscusstheimplicationsofourfindingsinforensicsapplicationsandintheprotectionofGWAS participantprivacy. Citation: Braun R, Rowe W, Schaefer C, Zhang J, Buetow K (2009) Needles in the Haystack: Identifying Individuals Present in Pooled Genomic Data. PLoS Genet5(10):e1000668.doi:10.1