Zook, J. M.Hansen, N. F.Olson, N. D.Chapman, L.Mullikin, J. C.Xiao, C.Sherry, S.Koren, S.Phillippy, A. M.Boutros, P. C.Sahraeian, S. M. E.Huang, V.Rouette, A.Alexander, N.Mason, C. E.Hajirasouliha, I.Ricketts, C.Lee, J.Tearle, R.Fiddes, I. T.Barrio, A. M.Wala, J.Carroll, A.Ghaffari, N.Rodriguez, O. L.Bashir, A.Jackman, S.Farrell, J. J.Wenger, A. M.Alkan, CanSöylev, A.Schatz, M. C.Garg, S.Church, G.Marschall, T.Chen, K.Fan, X.English, A. C.Rosenfeld, J. A.Zhou, W.Mills, R. E.Sage, J. M.Davis, J. R.Kaiser, M. D.Oliver, J. S.Catalano, A. P.Chaisson, M. J. P.Spies, N.Sedlazeck, F. J.Salit, M.2022-04-272021-03-032022-04-2720201087-0156http://hdl.handle.net/11693/75718.2New 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.EnglishArticle10.1038/s41587-020-0640-y