An Evaluation of Different Target Enrichment Methods in Pooled Sequencing Designs for Complex Disease Association Studies 英文参考文献.docVIP
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An Evaluation of Different Target Enrichment Methods in Pooled Sequencing Designs for Complex Disease Association Studies 英文参考文献
AnEvaluationofDifferentTargetEnrichmentMethodsin
PooledSequencingDesignsforComplexDisease
AssociationStudies
AaronG.Day-Williams1,KirstenMcLay1,2,EleanorDrury1,SarahEdkins1,AlisonJ.Coffey1 ,Aarno
Palotie1,3,4,5,EleftheriaZeggini1*
1Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, United Kingdom, 2The Genome Analysis Centre, Norwich, United
Kingdom,3InstituteforMolecularMedicineFinland(FIMM),UniversityofHelsinki,Helsinki,Finland,4PrograminMedicalandPopulationGeneticsandGeneticAnalysis
Platform, The Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America, 5Department of Medical Genetics, University of Helsinki and
UniversityCentralHospital,Helsinki,Finland
Abstract
Pooledsequencingcanbeacost-effectiveapproachtodiseasevariantdiscovery,butitsapplicabilityinassociationstudies
remainsunclear.Wecomparesequenceenrichmentmethodscoupledtonext-generationsequencinginnon-indexedpools
of1,2,10,20and50individualsandassesstheirabilitytodiscovervariantsandtoestimatetheirallelefrequencies.Wefind
that pooled resequencing is most usefully applied as a variant discovery tool due to limitations in estimating allele
frequencywithhighenoughaccuracyforassociationstudies,andthatin-solutionhybrid-captureperformsbestamongthe
enrichmentmethodsexaminedregardlessofpoolsize.
Citation: Day-Williams AG, McLay K, Drury E, Edkins S, Coffey AJ, et al. (2011) An Evaluation of Different Target Enrichment Methods in Pooled Sequencing
DesignsforComplexDiseaseAssociationStudies.PLoSONE6(11):e26279.doi:10.1371/journal.pone.0026279
Editor:You-QiangSong,TheUniversityofHongKong,HongKong
ReceivedJuly5,2011;AcceptedSeptember23,2011;PublishedNovember1,2011
Copyright:?2011Day-Williamsetal.Thisisanopen-accessarticledistributedunderthetermsoftheCreativeCommonsAttributionLicense,whichpermits
unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited.
Funding:ThisworkissupportedbytheWellcomeTrust(WT088885/
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