PT - JOURNAL ARTICLE AU - María C. Ávila-Arcos AU - Marcela Sandoval-Velasco AU - Hannes Schroeder AU - Meredith L. Carpenter AU - Anna-Sapfo Malaspinas AU - Nathan Wales AU - Fernando Peñaloza AU - Carlos D. Bustamante AU - M. Thomas P. Gilbert TI - Comparative Performance of Two Whole Genome Capture Methodologies on Ancient DNA Illumina Libraries AID - 10.1101/007419 DP - 2014 Jan 01 TA - bioRxiv PG - 007419 4099 - http://biorxiv.org/content/early/2014/07/24/007419.short 4100 - http://biorxiv.org/content/early/2014/07/24/007419.full AB - The application of whole genome capture (WGC) methods to ancient DNA (aDNA) promises to increase the efficiency of ancient genome sequencing.We 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.Our 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.Our findings provide insights for researchers planning to perform WGC on aDNA, and suggest future tests and optimization to improve WGC efficiency.