A robust benchmark for detection of germline large deletions and insertions

Justin M. Zook, Nancy F. Hansen, Nathan D. Olson, Lesley Chapman, James C. Mullikin, Chunlin Xiao, Stephen Sherry, Sergey Koren, Adam M. Phillippy, Paul C. Boutros, Sayed Mohammad E. Sahraeian, Vincent Huang, Alexandre Rouette, Noah Alexander, Christopher E. Mason, Iman Hajirasouliha, Camir Ricketts, Joyce Lee, Rick Tearle, Ian T. FiddesAlvaro Martinez Barrio, Jeremiah Wala, Andrew Carroll, Noushin Ghaffari, Oscar L. Rodriguez, Ali Bashir, Shaun Jackman, John J. Farrell, Aaron M. Wenger, Can Alkan, Arda Soylev, Michael C. Schatz, Shilpa Garg, George Church, Tobias Marschall, Ken Chen, Xian Fan, Adam C. English, Jeffrey A. Rosenfeld, Weichen Zhou, Ryan E. Mills, Jay M. Sage, Jennifer R. Davis, Michael D. Kaiser, John S. Oliver, Anthony P. Catalano, Mark J.P. Chaisson, Noah Spies, Fritz J. Sedlazeck, Marc Salit

Research output: Contribution to journalArticlepeer-review

163 Scopus citations


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 a 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 Consortium integrated 19 sequence-resolved variant calling methods from diverse technologies. The final benchmark set contains 12,745 isolated, sequence-resolved insertion (7,281) and deletion (5,464) calls ≥50 base pairs (bp). The Tier 1 benchmark regions, for which any extra calls are putative false positives, cover 2.51 Gbp and 5,262 insertions and 4,095 deletions supported by ≥1 diploid assembly. We demonstrate that 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.

Original languageEnglish
Pages (from-to)1347-1355
Number of pages9
JournalNature Biotechnology
Issue number11
StatePublished - 1 Nov 2020


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