A robust benchmark for detection of germline large deletions and insertions.

Abstract

New technologies and analysis methods are enabling genomic structural variants (SVs) to be detected with ever-increasing accuracy, resolution, and comprehensiveness. To help translate these methods to routine research and clinical practice, we developed the first sequence-resolved benchmark set for identification of both false negative and false positive germline large insertions and deletions. To create this benchmark for a broadly consented son in a Personal Genome Project trio with broadly available cells and DNA, the Genome in a Bottle (GIAB) Consortium integrated 19 sequence-resolved variant calling methods from diverse technologies. The final benchmark set contains 12745 isolated, sequence-resolved insertion (7281) and deletion (5464) calls ≥50 base pairs (bp). The Tier 1 benchmark regions, for which any extra calls are putative false positives, cover 2.51 Gbp and 5262 insertions and 4095 deletions supported by ≥1 diploid assembly. We demonstrate the benchmark set reliably identifies false negatives and false positives in high-quality SV callsets from short-, linked-, and long-read sequencing and optical mapping.