A robust benchmark for detection of germline large deletions and insertions.
Journal
Nature biotechnology
ISSN: 1546-1696
Titre abrégé: Nat Biotechnol
Pays: United States
ID NLM: 9604648
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
16
07
2019
accepted:
28
04
2020
pubmed:
17
6
2020
medline:
16
12
2020
entrez:
17
6
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32541955
doi: 10.1038/s41587-020-0538-8
pii: 10.1038/s41587-020-0538-8
pmc: PMC8454654
mid: NIHMS1589143
doi:
Types de publication
Journal Article
Research Support, N.I.H., Intramural
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
1347-1355Subventions
Organisme : Intramural NIST DOC
ID : 9999-NIST
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI151059
Pays : United States
Commentaires et corrections
Type : ErratumIn
Références
Sebat, J. et al. Strong association of de novo copy number mutations with autism. Science 316, 445–449 (2007).
doi: 10.1126/science.1138659
pubmed: 17363630
pmcid: 2993504
Merker, J. D. et al. Long-read genome sequencing identifies causal structural variation in a Mendelian disease. Genet. Med. 20, 159–163 (2018).
doi: 10.1038/gim.2017.86
pubmed: 28640241
Mantere, T., Kersten, S. & Hoischen, A. Long-read sequencing emerging in medical genetics. Front. Genet. 10, 426 (2019).
doi: 10.3389/fgene.2019.00426
pubmed: 31134132
pmcid: 6514244
Roses, A. D. et al. Structural variants can be more informative for disease diagnostics, prognostics and translation than current SNP mapping and exon sequencing. Expert Opin. Drug Metab. Toxicol. 12, 135–147 (2016).
doi: 10.1517/17425255.2016.1133586
pubmed: 26727306
Chiang, C. et al. The impact of structural variation on human gene expression. Nat. Genet. 49, 692–699 (2017).
doi: 10.1038/ng.3834
pubmed: 28369037
pmcid: 5406250
Chaisson, M. J. P. et al. Multi-platform discovery of haplotype-resolved structural variation in human genomes. Nat. Commun. 10, 1784 (2019).
doi: 10.1038/s41467-018-08148-z
pubmed: 30992455
pmcid: 30992455
Ball, M. P. et al. A public resource facilitating clinical use of genomes. Proc. Natl Acad. Sci. USA 109, 11920–11927 (2012).
doi: 10.1073/pnas.1201904109
pubmed: 22797899
Zook, J. M. et al. Extensive sequencing of seven human genomes to characterize benchmark reference materials. Sci. Data 3, 160025 (2016).
doi: 10.1038/sdata.2016.25
pubmed: 27271295
pmcid: 4896128
Zook, J. M. et al. An open resource for accurately benchmarking small variant and reference calls. Nat. Biotechnol. 37, 561–566 (2019).
doi: 10.1038/s41587-019-0074-6
pubmed: 30936564
pmcid: 6500473
Sebat, J. et al. Large-scale copy number polymorphism in the human genome. Science 305, 525–528 (2004).
doi: 10.1126/science.1098918
pubmed: 15273396
Spies, N. et al. Genome-wide reconstruction of complex structural variants using read clouds. Nat. Methods 14, 915–920 (2017).
doi: 10.1038/nmeth.4366
pubmed: 28714986
pmcid: 5578891
Marks, P. et al. Resolving the full spectrum of human genome variation using Linked-Reads. Genome Res. 29, 635–645 (2019).
doi: 10.1101/gr.234443.118
pubmed: 30894395
pmcid: 6442396
Karaoglanoglu, F. et al. VALOR2: characterization of large-scale structural variants using linked-reads. Genome Biol. 21, 72 (2020).
doi: 10.1186/s13059-020-01975-8
pubmed: 32192518
pmcid: 7083023
Weisenfeld, N. I., Kumar, V., Shah, P., Church, D. M. & Jaffe, D. B. Direct determination of diploid genome sequences. Genome Res. 27, 757–767 (2017).
doi: 10.1101/gr.214874.116
pubmed: 5411770
pmcid: 5411770
Sedlazeck, F. J. et al. Accurate detection of complex structural variations using single-molecule sequencing. Nat. Methods 15, 461–468 (2018).
doi: 10.1038/s41592-018-0001-7
pubmed: 5990442
pmcid: 5990442
Cretu Stancu, M. et al. Mapping and phasing of structural variation in patient genomes using nanopore sequencing. Nat. Commun. 8, 1326 (2017).
doi: 10.1038/s41467-017-01343-4
pubmed: 29109544
pmcid: 29109544
Chaisson, M. J. P. et al. Resolving the complexity of the human genome using single-molecule sequencing. Nature 517, 608–611 (2014).
doi: 10.1038/nature13907
pubmed: 25383537
pmcid: 25383537
Chin, C.-S. et al. Phased diploid genome assembly with single-molecule real-time sequencing. Nat. Methods 13, 1050–1054 (2016).
doi: 10.1038/nmeth.4035
pubmed: 27749838
pmcid: 27749838
Koren, S. et al. De novo assembly of haplotype-resolved genomes with trio binning. Nat. Biotechnol. https://doi.org/10.1038/nbt.4277 (2018).
Kaiser, M. D. et al. Automated structural variant verification in human genomes using single-molecule electronic DNA mapping. Preprint at https://www.biorxiv.org/content/10.1101/140699v1.full (2017).
Lam, E. T. et al. Genome mapping on nanochannel arrays for structural variation analysis and sequence assembly. Nat. Biotechnol. 30, 771–776 (2012).
doi: 10.1038/nbt.2303
pubmed: 22797562
Barseghyan, H. et al. Next-generation mapping: a novel approach for detection of pathogenic structural variants with a potential utility in clinical diagnosis. Genome Med. 9, 90 (2017).
doi: 10.1186/s13073-017-0479-0
pubmed: 29070057
pmcid: 5655859
Zook, J. M. et al. Integrating human sequence data sets provides a resource of benchmark SNP and indel genotype calls. Nat. Biotechnol. 32, 246–251 (2014).
doi: 10.1038/nbt.2835
pubmed: 24531798
Krusche, P. et al. Best practices for benchmarking germline small-variant calls in human genomes. Nat. Biotechnol. 37, 555–560 (2019).
doi: 10.1038/s41587-019-0054-x
pubmed: 30858580
pmcid: 6699627
Cleveland, M. H., Zook, J. M., Salit, M. & Vallone, P. M. Determining performance metrics for targeted next-generation sequencing panels using reference materials. J. Mol. Diagn. 20, 583–590 (2018).
Wenger, A. M. et al. Highly-accurate long-read sequencing improves variant detection and assembly of a human genome. Nat. Biotechnol. 37, 1155-1162 (2019).
Sudmant, P. H. et al. An integrated map of structural variation in 2,504 human genomes. Nature 526, 75–81 (2015).
doi: 10.1038/nature15394
pubmed: 26432246
pmcid: 4617611
Conrad, D. F. et al. Origins and functional impact of copy number variation in the human genome. Nature 464, 704–712 (2010).
doi: 10.1038/nature08516
pubmed: 19812545
Parikh, H. et al. svclassify: a method to establish benchmark structural variant calls. BMC Genomics 17, 64 (2016).
doi: 10.1186/s12864-016-2366-2
pubmed: 26772178
pmcid: 4715349
Pang, A. W. et al. Towards a comprehensive structural variation map of an individual human genome. Genome Biol. 11, R52 (2010).
doi: 10.1186/gb-2010-11-5-r52
pubmed: 20482838
pmcid: 2898065
Mu, J. C. et al. Leveraging long read sequencing from a single individual to provide a comprehensive resource for benchmarking variant calling methods. Sci. Rep. 5, 14493 (2015).
doi: 10.1038/srep14493
pubmed: 26412485
pmcid: 4585973
Huddleston, J. et al. Discovery and genotyping of structural variation from long-read haploid genome sequence data. Genome Res. 27, 677–685 (2017).
doi: 10.1101/gr.214007.116
pubmed: 27895111
pmcid: 27895111
English, A. C. et al. Assessing structural variation in a personal genome-towards a human reference diploid genome. BMC Genomics 16, 286 (2015).
doi: 10.1186/s12864-015-1479-3
pubmed: 25886820
pmcid: 4490614
Audano, P. A. et al. Characterizing the major structural variant alleles of the human genome. Cell 176, 663–675 (2019).
doi: 10.1016/j.cell.2018.12.019
pubmed: 30661756
pmcid: 30661756
Wala, J. A. et al. SvABA: genome-wide detection of structural variants and indels by local assembly. Genome Res. 28, 581–591 (2018).
doi: 10.1101/gr.221028.117
pubmed: 29535149
pmcid: 5880247
Cameron, D. L. et al. GRIDSS: sensitive and specific genomic rearrangement detection using positional de Bruijn graph assembly. Genome Res. 27, 2050–2060 (2017).
doi: 10.1101/gr.222109.117
pubmed: 29097403
pmcid: 5741059
Nattestad, M. et al. Complex rearrangements and oncogene amplifications revealed by long-read DNA and RNA sequencing of a breast cancer cell line. Genome Res. 28, 1126–1135 (2018).
doi: 10.1101/gr.231100.117
pubmed: 6071638
pmcid: 6071638
Lee, A. Y. et al. Combining accurate tumor genome simulation with crowdsourcing to benchmark somatic structural variant detection. Genome Biol. 19, 188 (2018).
doi: 10.1186/s13059-018-1539-5
pubmed: 30400818
pmcid: 30400818
Xia, L. C. et al. SVEngine: an efficient and versatile simulator of genome structural variations with features of cancer clonal evolution. Gigascience 7, https://doi.org/10.1093/gigascience/giy081 (2018).
Jeffares, D. C. et al. Transient structural variations have strong effects on quantitative traits and reproductive isolation in fission yeast. Nat. Commun. 8, 14061 (2017).
doi: 10.1038/ncomms14061
pubmed: 28117401
pmcid: 5286201
Spies, N., Zook, J. M., Salit, M. & Sidow, A. svviz: a read viewer for validating structural variants. Bioinformatics 31, 3994–3996 (2015).
Song, J. H. T., Lowe, C. B. & Kingsley, D. M. Characterization of a human-specific tandem repeat associated with bipolar disorder and Schizophrenia. Am. J. Hum. Genet. 103, 421–430 (2018).
doi: 10.1016/j.ajhg.2018.07.011
pubmed: 30100087
pmcid: 30100087
Chapman, L. M. et al. SVCurator: a crowdsourcing app to visualize evidence of structural variants for the human genome. Preprint at https://www.biorxiv.org/content/10.1101/581264v1 (2019).
Collins, R. L. et al. An open resource of structural variation for medical and population genetics. Preprint at https://www.biorxiv.org/content/10.1101/578674v1 (2019).
Hickey, G. et al. Genotyping structural variants in pangenome graphs using the vg toolkit. Genome Biol. 21, 35 (2020).
doi: 10.1186/s13059-020-1941-7
pubmed: 32051000
pmcid: 7017486
Chen, S. et al. Paragraph: a graph-based structural variant genotyper for short-read sequence data. Genome Biol. 20, 291 (2019).
doi: 10.1186/s13059-019-1909-7
pubmed: 31856913
pmcid: 6921448
Falconer, E. et al. DNA template strand sequencing of single-cells maps genomic rearrangements at high resolution. Nat. Methods 9, 1107–1112 (2012).
doi: 10.1038/nmeth.2206
pubmed: 23042453
pmcid: 3580294
Miga, K. H. et al. Telomere-to-telomere assembly of a complete human X chromosome. Preprint at https://www.biorxiv.org/content/10.1101/735928v3 (2019).
Jain, M. et al. Nanopore sequencing and assembly of a human genome with ultra-long reads. Nat. Biotechnol. 36, 338–345 (2018).
doi: 10.1038/nbt.4060
pubmed: 29431738
pmcid: 5889714