design: Library construction was performed as described in Fisher et al. (Genome Biology 2011), with the following modifications: initial genomic DNA input into shearing was reduced from 3µg to 10-100ng in 50µL of solution. For adapter ligation, Illumina paired end adapters were replaced with palindromic forked adapters, purchased from Integrated DNA Technologies, with unique 8 base molecular barcode sequences included in the adapter sequence to facilitate downstream pooling. With the exception of the palindromic forked adapters, the reagents used for end repair, A-base addition, adapter ligation, and library enrichment PCR were purchased from KAPA Biosciences in 96-reaction kits. In addition, during the post-enrichment SPRI cleanup, elution volume was reduced to 30µL to maximize library concentration, and a vortexing step was added to maximize the amount of template eluted. After library construction, hybridization and capture were performed using the relevant components of Illumina's Rapid Capture Exome Kit and following the manufacturer's suggested protocol, with the following exceptions: first, all libraries within a library construction plate were pooled prior to hybridization. Second, the Midi plate from Illumina's Rapid Capture Exome Kit was replaced with a skirted PCR plate to facilitate automation. All hybridization and capture steps were automated on the Agilent Bravo liquid handling system. After post-capture enrichment, library pools were quantified using qPCR (automated assay on the Agilent Bravo), using a kit purchased from KAPA Biosystems with probes specific to the ends of the adapters. Based on qPCR quantification, libraries were normalized to 2nM, then denatured using 0.1 N NaOH on the Hamilton Starlet. After denaturation, libraries were diluted to 20pM using hybridization buffer purchased from Illumina. Cluster amplification of denatured templates was performed according to the manufacturer's protocol Illumina sequencers. The flowcells are then analyzed using RTA v.1.18.64 or later. Each pool of whole exome libraries was run on paired 76bp runs, with an 8 base index sequencing read to identify molecular indices, across the number of lanes needed to meet coverage for all libraries in the pool.