Allelic bias when performing in-solution enrichment of ancient human DNA

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dc.contributor.authorDavidson, R.
dc.contributor.authorWilliams, M.P.
dc.contributor.authorRoca-Rada, X.
dc.contributor.authorKassadjikova, K.
dc.contributor.authorTobler, R.
dc.contributor.authorFehren-Schmitz, L.
dc.contributor.authorLlamas, B.
dc.date.issued2023
dc.descriptionFirst published: 15 September 2023
dc.description.abstractIn-solution hybridisation enrichment of genetic variation is a valuable methodology in human paleogenomics. It allows enrichment of endogenous DNA by targeting genetic markers that are comparable between sequencing libraries. Many studies have used the 1240k reagent-which enriches 1,237,207 genome-wide SNPs-since 2015, though access was restricted. In 2021, Twist Biosciences and Daicel Arbor Biosciences independently released commercial kits that enabled all researchers to perform enrichments for the same 1240 k SNPs. We used the Daicel Arbor Biosciences Prime Plus kit to enrich 132 ancient samples from three continents. We identified a systematic assay bias that increases genetic similarity between enriched samples and that cannot be explained by batch effects. We present the impact of the bias on population genetics inferences (e.g. Principal Components Analysis, ƒ-statistics) and genetic relatedness (READ). We compare the Prime Plus bias to that previously reported of the legacy 1240k enrichment assay. In ƒ-statistics, we find that all Prime-Plus-generated data exhibit artefactual excess shared drift, such that within-continent relationships cannot be correctly determined. The bias is more subtle in READ, though interpretation of the results can still be misleading in specific contexts. We expect the bias may affect analyses we have not yet tested. Our observations support previously reported concerns for the integration of different data types in paleogenomics. We also caution that technological solutions to generate 1240k data necessitate a thorough validation process before their adoption in the paleogenomic community.
dc.description.statementofresponsibilityRoberta Davidson, Matthew P. Williams, Xavier Roca-Rada, Kalina Kassadjikova, Raymond Tobler, Lars Fehren-Schmitz, Bastien Llamas
dc.identifier.citationMolecular Ecology Resources, 2023; 23(8):1823-1840
dc.identifier.doi10.1111/1755-0998.13869
dc.identifier.issn1471-8278
dc.identifier.issn1755-0998
dc.identifier.orcidDavidson, R. [0000-0002-9909-2018]
dc.identifier.orcidTobler, R. [0000-0002-4603-1473]
dc.identifier.orcidLlamas, B. [0000-0002-5550-9176]
dc.identifier.urihttps://hdl.handle.net/2440/139555
dc.language.isoen
dc.publisherWiley
dc.relation.granthttp://purl.org/au-research/grants/arc/FT170100448
dc.relation.granthttp://purl.org/au-research/grants/arc/DE190101069
dc.rights© 2023 The Authors. Molecular Ecology Resources published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
dc.source.urihttps://doi.org/10.1111/1755-0998.13869
dc.subject1240k
dc.subjectancient DNA
dc.subjectbias
dc.subjectenrichment
dc.titleAllelic bias when performing in-solution enrichment of ancient human DNA
dc.typeJournal article
pubs.publication-statusPublished

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