Imputation of ancient human genomes.
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Peer-reviewed
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Abstract
Due to postmortem DNA degradation and microbial colonization, most ancient genomes have low depth of coverage, hindering genotype calling. Genotype imputation can improve genotyping accuracy for low-coverage genomes. However, it is unknown how accurate ancient DNA imputation is and whether imputation introduces bias to downstream analyses. Here we re-sequence an ancient trio (mother, father, son) and downsample and impute a total of 43 ancient genomes, including 42 high-coverage (above 10x) genomes. We assess imputation accuracy across ancestries, time, depth of coverage, and sequencing technology. We find that ancient and modern DNA imputation accuracies are comparable. When downsampled at 1x, 36 of the 42 genomes are imputed with low error rates (below 5%) while African genomes have higher error rates. We validate imputation and phasing results using the ancient trio data and an orthogonal approach based on Mendel's rules of inheritance. We further compare the downstream analysis results between imputed and high-coverage genomes, notably principal component analysis, genetic clustering, and runs of homozygosity, observing similar results starting from 0.5x coverage, except for the African genomes. These results suggest that, for most populations and depths of coverage as low as 0.5x, imputation is a reliable method that can improve ancient DNA studies.
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Acknowledgements: We are thankful to Isabel Alves, Samuel Neuenschwander and J. Víctor Moreno-Mayar for fruitful discussions that contributed to improving this study. B.S.d.M. was supported by a Swiss National Science Foundation (SNSF) project grant (PP00P3_176977) to O.D. and by a European Research Council grant (grant agreement no. 679330) to A.-S.M. S.R. was supported by Swiss National Science Foundation (SNSF) project grant (PP00P3_176977). D.I.C.D. was supported by the European Research Council grant (grant agreement no. 679330) to A.-S.M. C.E.G.A. was supported by the National Institute of General Medical Sciences of the National Institutes of Health under award number R35GM142939. N.N.J. was supported by Aarhus University Research Foundation. H.S. was supported by the European Research Council (grant agreement no. 101045643).
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2041-1723