Allelic bias when performing in-solution enrichment of ancient human DNA

In-solution enrichment is a widely used technique for targeted capture of ancient DNA (aDNA) from degraded samples. However, the extent to which this method introduces allelic bias has not been systematically evaluated. Here, we investigate allelic bias in in-solution enrichment by comparing whole-genome shotgun sequencing data with enrichment data from the same ancient human samples. We find that in-solution enrichment introduces significant allelic bias, with certain alleles being preferentially captured over others. The magnitude of this bias varies across genomic positions and is influenced by factors including the design of capture probes and the degree of DNA degradation. Our results demonstrate that allelic bias in enrichment data can lead to systematic errors in population genetic analyses and highlight the importance of accounting for this bias when interpreting ancient genomic data.