Comparative Performance of Two Whole Genome Capture Methodologies on Ancient DNA Illumina Libraries

O_LIThe application of whole genome capture (WGC) methods to ancient DNA (aDNA) promises to increase the efficiency of ancient genome sequencing.\nC_LIO_LIWe compared the performance of two recently developed WGC methods in enriching human aDNA within Illumina libraries built using both double-stranded (DSL) and single-stranded (SSL) build protocols. Although both methods effectively enriched aDNA, one consistently produced marginally better results, giving us the opportunity to further explore the parameters influencing WGC experiments.\nC_LIO_LIOur results suggest that bait length has an important influence on library enrichment. Moreover, we show that WGC biases against the shorter molecules that are enriched in SSL preparation protocols. Therefore application of WGC to such samples is not recommended without future optimization. Lastly, we document the effect of WGC on other features including clonality, GC composition and repetitive DNA content of captured libraries.\nC_LIO_LIOur findings provide insights for researchers planning to perform WGC on aDNA, and suggest future tests and optimization to improve WGC efficiency.\nC_LI