Department of Computational Biology, University of Lausanne, Lausanne, Switzerland.
Swiss Institute of Bioinformatics, University of Lausanne, Lausanne, Switzerland.
Nat Commun. 2023 Jun 20;14(1):3660. doi: 10.1038/s41467-023-39202-0.
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.
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，阻碍了基因型的检测。基因型推断可以提高低覆盖度基因组的基因分型准确性。然而，目前还不清楚古代 DNA 推断的准确性如何，以及推断是否会给下游分析带来偏差。在这里，我们重新测序了一个古代一家三口（母亲、父亲、儿子），并对总共 43 个古代基因组进行了下采样和推断，其中包括 42 个高覆盖度（高于 10x）的基因组。我们评估了推断在不同血统、时间、覆盖深度和测序技术中的准确性。我们发现，古代和现代 DNA 推断的准确性相当。当在 1x 下进行下采样时，42 个基因组中有 36 个的推断错误率较低（低于 5%），而非洲基因组的错误率较高。我们使用古代一家三口的数据和基于孟德尔遗传规律的正交方法来验证推断和相位结果。我们进一步比较了推断和高覆盖度基因组的下游分析结果，特别是主成分分析、遗传聚类和纯合性运行，从 0.5x 覆盖度开始就观察到了相似的结果，除了非洲基因组。这些结果表明，对于大多数人群和低至 0.5x 的覆盖深度，推断是一种可靠的方法，可以提高古代 DNA 研究的准确性。
Zotero 插件
