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. Fiddes; Alvaro 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

doi:10.1038/s41587-020-0538-8

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

Bioinformatics & Computational Biology

Research output: Contribution to journal › Article › peer-review

159 Scopus citations

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 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 language	English (US)
Pages (from-to)	1347-1355
Number of pages	9
Journal	Nature biotechnology
Volume	38
Issue number	11
DOIs	https://doi.org/10.1038/s41587-020-0538-8
State	Published - Nov 1 2020

ASJC Scopus subject areas

Biotechnology
Bioengineering
Applied Microbiology and Biotechnology
Molecular Medicine
Biomedical Engineering

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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., ... Salit, M. (2020). A robust benchmark for detection of germline large deletions and insertions. Nature biotechnology, 38(11), 1347-1355. https://doi.org/10.1038/s41587-020-0538-8

Zook, JM, Hansen, NF, Olson, ND, Chapman, L, Mullikin, JC, Xiao, C, Sherry, S, Koren, S, Phillippy, AM, Boutros, PC, Sahraeian, SME, Huang, V, Rouette, A, Alexander, N, Mason, CE, Hajirasouliha, I, Ricketts, C, Lee, J, Tearle, R, Fiddes, IT, Barrio, AM, Wala, J, Carroll, A, Ghaffari, N, Rodriguez, OL, Bashir, A, Jackman, S, Farrell, JJ, Wenger, AM, Alkan, C, Soylev, A, Schatz, MC, Garg, S, Church, G, Marschall, T, Chen, K, Fan, X, English, AC, Rosenfeld, JA, Zhou, W, Mills, RE, Sage, JM, Davis, JR, Kaiser, MD, Oliver, JS, Catalano, AP, Chaisson, MJP, Spies, N, Sedlazeck, FJ & Salit, M 2020, 'A robust benchmark for detection of germline large deletions and insertions', Nature biotechnology, vol. 38, no. 11, pp. 1347-1355. https://doi.org/10.1038/s41587-020-0538-8

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title = "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 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.",

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

note = "Publisher Copyright: {\textcopyright} 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.",

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doi = "10.1038/s41587-020-0538-8",

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T1 - A robust benchmark for detection of germline large deletions and insertions

AU - Zook, Justin M.

AU - Hansen, Nancy F.

AU - Olson, Nathan D.

AU - Chapman, Lesley

AU - Mullikin, James C.

AU - Xiao, Chunlin

AU - Sherry, Stephen

AU - Koren, Sergey

AU - Phillippy, Adam M.

AU - Boutros, Paul C.

AU - Sahraeian, Sayed Mohammad E.

AU - Huang, Vincent

AU - Rouette, Alexandre

AU - Alexander, Noah

AU - Mason, Christopher E.

AU - Hajirasouliha, Iman

AU - Ricketts, Camir

AU - Lee, Joyce

AU - Tearle, Rick

AU - Fiddes, Ian T.

AU - Barrio, Alvaro Martinez

AU - Wala, Jeremiah

AU - Carroll, Andrew

AU - Ghaffari, Noushin

AU - Rodriguez, Oscar L.

AU - Bashir, Ali

AU - Jackman, Shaun

AU - Farrell, John J.

AU - Wenger, Aaron M.

AU - Alkan, Can

AU - Soylev, Arda

AU - Schatz, Michael C.

AU - Garg, Shilpa

AU - Church, George

AU - Marschall, Tobias

AU - Chen, Ken

AU - Fan, Xian

AU - English, Adam C.

AU - Rosenfeld, Jeffrey A.

AU - Zhou, Weichen

AU - Mills, Ryan E.

AU - Sage, Jay M.

AU - Davis, Jennifer R.

AU - Kaiser, Michael D.

AU - Oliver, John S.

AU - Catalano, Anthony P.

AU - Chaisson, Mark J.P.

AU - Spies, Noah

AU - Sedlazeck, Fritz J.

AU - Salit, Marc

PY - 2020/11/1

Y1 - 2020/11/1

N2 - 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.

AB - 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.

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A robust benchmark for detection of germline large deletions and insertions

Abstract

ASJC Scopus subject areas

MD Anderson CCSG core facilities

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