Ancient human trio (Koszyce)

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 downsample and impute 43 ancient genomes, 42 of which are high-coverage (above 10x) and three constitute a trio (mother, father and son). We assess imputation accuracy across ancestry, time, depth of coverage, and sequencing technology. We find that ancient and modern DNA imputation accuracies are comparable. We impute 36 of the 42 1x genomes with low error rates (below 5%) and estimate higher error rates for African genomes. 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 African genomes. These results suggest that, for most populations and depths of coverage as low as 0.5x, imputation is a reliable method with potential improve ancient DNA studies.