Imputation of ancient human genomes

Bárbara Sousa da Mota; Simone Rubinacci; Diana Ivette Cruz Dávalos; Carlos Eduardo G. Amorim; Martin Sikora; Niels Nørkjær Johannsen; Marzena Szmyt; Piotr Włodarczak; Anita Szczepanek; Marcin M. Przybyła; Hannes Schroeder; Morten E. Allentoft; Eske Willerslev; Anna Sapfo Malaspinas; Olivier Delaneau

doi:10.1038/s41467-023-39202-0

Imputation of ancient human genomes

Bárbara Sousa da Mota, Simone Rubinacci, Diana Ivette Cruz Dávalos, Carlos Eduardo G. Amorim, Martin Sikora, Niels Nørkjær Johannsen, Marzena Szmyt, Piotr Włodarczak, Anita Szczepanek, Marcin M. Przybyła, Hannes Schroeder, Morten E. Allentoft, Eske Willerslev, Anna Sapfo Malaspinas^*, Olivier Delaneau^*

^*Corresponding author af dette arbejde

Institut for Kultur og Samfund - Afdeling for Arkæologi og Kulturarvsstudier

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avis › Tidsskriftartikel › Forskning › peer review

22 Citationer (Scopus)

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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.

Originalsprog	Engelsk
Artikelnummer	3660
Tidsskrift	Nature Communications
Vol/bind	14
Nummer	1
Sider (fra-til)	1-17
ISSN	2041-1723
DOI	https://doi.org/10.1038/s41467-023-39202-0
Status	Udgivet - dec. 2023

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10.1038/s41467-023-39202-0Licens: CC BY

Imputation of ancient human genomes_VoRForlagets udgivne version, 21 MBLicens: CC BY

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Sousa da Mota, B., Rubinacci, S., Cruz Dávalos, D. I., G. Amorim, C. E., Sikora, M., Johannsen, N. N., Szmyt, M., Włodarczak, P., Szczepanek, A., Przybyła, M. M., Schroeder, H., Allentoft, M. E., Willerslev, E., Malaspinas, A. S., & Delaneau, O. (2023). Imputation of ancient human genomes. Nature Communications, 14(1), 1-17. Artikel 3660. https://doi.org/10.1038/s41467-023-39202-0

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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{\textquoteright}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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AU - Rubinacci, Simone

AU - Cruz Dávalos, Diana Ivette

AU - G. Amorim, Carlos Eduardo

AU - Sikora, Martin

AU - Johannsen, Niels Nørkjær

AU - Szmyt, Marzena

AU - Włodarczak, Piotr

AU - Szczepanek, Anita

AU - Przybyła, Marcin M.

AU - Schroeder, Hannes

AU - Allentoft, Morten E.

AU - Willerslev, Eske

AU - Malaspinas, Anna Sapfo

AU - Delaneau, Olivier

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N2 - 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.

AB - 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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KW - Genotype

KW - Genotyping Techniques/methods

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JF - Nature Communications

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ER -

Imputation of ancient human genomes

Abstract

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