Performance comparison of exome DNA sequencing technologies

Whole exome sequencing (exome-seq) by high-throughput sequencing of target-enriched genomic DNA has become increasingly common in basic and translational research as a means of interrogating the interpretable part of the human genome at relatively low cost. Using the same human sample, we performed an unbiased comparison of three major commercial exome-seq platforms from Agilent, Illumina and Nimblegen. These platforms differ significantly in their probe design, targeted genomic regions, on-target bait density and biochemical approach. Platforms with high-density overlapping baits have increased enrichment efficiency and variant detection sensitivity, but cover fewer genomic regions than those with lower density probes. Moreover, the different platforms target distinct exomic features. Comparison to whole genome sequencing demonstrates particular advantages of exome-seq and recommends sequencing levels for each platform. Overall, this study has significant general implications for targeted genomic sequencing and especially for the analysis of human disease and variation.