Imputation of ancient human genomes.
Imputation of ancient human genomes.
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DOI：
10.1038/s41467-023-39202-0
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发表时间：
2023-06-20
影响因子：
16.6
通讯作者：
Delaneau, Olivier
中科院分区：
文献类型：
--
作者：
Sousa da Mota, Barbara;Rubinacci, Simone;Cruz Davalos, Diana Ivette;Amorim, Carlos Eduardo G.;Sikora, Martin;Johannsen, Niels N.;Szmyt, Marzena H.;Wlodarczak, Piotr;Szczepanek, Anita;Przybyla, Marcin M.;Schroeder, Hannes;Allentoft, Morten E.;Willerslev, Eske;Malaspinas, Anna-Sapfo;Delaneau, Olivier
由于死后DNA降解和微生物定殖，大多数古代基因组的覆盖深度较低，阻碍了基因型调用。基因型插补可以提高低覆盖率基因组的基因分型准确性。然而，目前尚不清楚古代DNA估算的准确性如何，以及估算是否会给下游分析带来偏倚。在这里，我们对一个古老的三人组（母亲、父亲、儿子）进行了重新测序，并对总共43个古老的基因组进行了下采样和估算，其中包括42个高覆盖率（超过10倍）的基因组。我们评估了不同血统、时间、覆盖深度和测序技术的插补准确性。我们发现古代和现代的DNA估算准确性是相当的。当以1x下采样时，42个基因组中的36个基因组的错误率较低（低于5%），而非洲基因组的错误率较高。我们验证插补和分阶段的结果，使用古老的三人组数据和孟德尔的遗传规则的基础上的正交方法。我们进一步比较了估算和高覆盖率基因组之间的下游分析结果，特别是主成分分析，遗传聚类和纯合性运行，从0.5x覆盖率开始观察到类似的结果，除了非洲基因组。这些结果表明，对于大多数人口和覆盖深度低至0.5倍，插补是一种可靠的方法，可以改善古代DNA研究。对于大多数古老的基因组，低测序深度限制了基因分型，限制了他们的研究。在这里，作者通过估计错误率和下游分析中引入的潜在偏倚来测试古人类基因组的插补性能。
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. For most ancient genomes, low sequencing depth restricts genotyping, limiting their study. Here, the authors test imputation performance of ancient human genomes by estimating error rates and potential bias introduced in downstream analyses.
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影响因子：
64.8
作者：
Bycroft C;Freeman C;Petkova D;Band G;Elliott LT;Sharp K;Motyer A;Vukcevic D;Delaneau O;O'Connell J;Cortes A;Welsh S;Young A;Effingham M;McVean G;Leslie S;Allen N;Donnelly P;Marchini J
通讯作者：
Marchini J
DOI：
10.1093/g3journal/jkac089
发表时间：
2022-05-30
期刊：
G3 (Bethesda, Md.)
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1073/pnas.1405138111
发表时间：
2014-05-06
影响因子：
11.1
作者：
Castellano, Sergi;Parra, Genis;Paeaebo, Svante
通讯作者：
Paeaebo, Svante
影响因子：
9.8
作者：
Browning, Brian L.;Browning, Sharon R.
通讯作者：
Browning, Sharon R.
影响因子：
3.3
作者：
Biddanda, Arjun;Steinrucken, Matthias;Novembre, John
通讯作者：
Novembre, John