The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.
Resolving the complexity of the human genome using single-molecule sequencing
Open accessAbstract
The human genome is arguably the most complete mammalian reference assembly, yet more than 160 euchromatic gaps remain and aspects of its structural variation remain poorly understood ten years after its completion. To identify missing sequence and genetic variation, here we sequence and analyse a haploid human genome (CHM1) using single-molecule, real-time DNA sequencing. We close or extend 55% of the remaining interstitial gaps in the human GRCh37 reference genome—78% of which carried long runs of degenerate short tandem repeats, often several kilobases in length, embedded within (G+C)-rich genomic regions. We resolve the complete sequence of 26,079 euchromatic structural variants at the base-pair level, including inversions, complex insertions and long tracts of tandem repeats. Most have not been previously reported, with the greatest increases in sensitivity occurring for events less than 5 kilobases in size. Compared to the human reference, we find a significant insertional bias (3:1) in regions corresponding to complex insertions and long short tandem repeats. Our results suggest a greater complexity of the human genome in the form of variation of longer and more complex repetitive DNA that can now be largely resolved with the application of this longer-read sequencing technology.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
The sequence of the human genome
Venter, J. C., Adams, M. D., Myers, E. W., Li, P. W., Mural, R. J., Sutton, G. G., Smith, H. O., Yandell, M., Evans, C. A., Holt, R. A., et al. (2001) · Science · doi:10.1126/science.1058040 · Cited by 13,909
Self-citationAn integrated map of genetic variation from 1,092 human genomes
The 1000 Genomes Project Consortium (2012) · Nature · doi:10.1038/nature11632 · Cited by 7,711
The International HapMap Project
†The International HapMap Consortium, Genotyping centres: Baylor College of Medicine and ParAllele BioScience, Gibbs, R. A., Belmont, J. W., Hardenbol, P., Willis, T. D., Yu, F., Chinese HapMap Consortium, Yang, H., Ch'ang, L.-Y., et al. (2003) · Nature · doi:10.1038/nature02168 · Cited by 6,057
Origins and functional impact of copy number variation in the human genome
The Wellcome Trust Case Control Consortium, Conrad, D. F., Pinto, D., Redon, R., Feuk, L., Gokcumen, O., Zhang, Y., Aerts, J., Andrews, T. D., Barnes, C., et al. (2010) · Nature · doi:10.1038/nature08516 · Cited by 1,970
Mapping copy number variation by population-scale genome sequencing
1000 Genomes Project, Mills, R. E., Walter, K., Stewart, C., Handsaker, R. E., Chen, K., Alkan, C., Abyzov, A., Yoon, S. C., Ye, K., et al. (2011) · Nature · doi:10.1038/nature09708 · Cited by 1,140
Self-citationA comprehensive map of mobile element insertion polymorphisms in humans
Stewart, C., Kural, D., Strömberg, M. P., Walker, J. A., Konkel, M. K., Stütz, A. M., Urban, A. E., Grubert, F., Lam, H. Y. K., Lee, W.-P., et al. (2011) · PLoS Genetics · doi:10.1371/journal.pgen.1002236 · Cited by 307
Cited by
A global reference for human genetic variation
The 1000 Genomes Project Consortium, authors, C., Auton, A., Abecasis, G. R., Steering committee, Altshuler, D. M., Durbin, R. M., Abecasis, G. R., Bentley, D. R., Chakravarti, A., et al. (2015) · Nature · doi:10.1038/nature15393 · Cited by 18,247
Self-citationAssembly of long, error-prone reads using repeat graphs
Kolmogorov, M., Yuan, J., Lin, Y., & Pevzner, P. A. (2019) · Nature Biotechnology · doi:10.1038/s41587-019-0072-8 · Cited by 5,986
Coming of age: ten years of next-generation sequencing technologies
Goodwin, S., McPherson, J. D., & McCombie, W. R. (2016) · Nature Reviews Genetics · doi:10.1038/nrg.2016.49 · Cited by 4,352
The complete sequence of a human genome
Nurk, S., Koren, S., Rhie, A., Rautiainen, M., Bzikadze, A. V., Mikheenko, A., Vollger, M. R., Altemose, N., Uralsky, L., Gershman, A., et al. (2022) · Science · doi:10.1126/science.abj6987 · Cited by 3,136
Self-citationTowards complete and error-free genome assemblies of all vertebrate species
Rhie, A., McCarthy, S. A., Fedrigo, O., Damas, J., Formenti, G., Koren, S., Uliano-Silva, M., Chow, W., Fungtammasan, A., Kim, J., et al. (2021) · Nature · doi:10.1038/s41586-021-03451-0 · Cited by 3,097
Self-citationTowards complete and error-free genome assemblies of all vertebrate species
Rhie, A., McCarthy, S. A., Fedrigo, O., Damas, J., Formenti, G., Koren, S., Uliano-Silva, M., Chow, W., Fungtammasan, A., Gedman, G. L., et al. (2020) · doi:10.1101/2020.05.22.110833 · Cited by 3,097
Self-citationOpportunities and challenges in long-read sequencing data analysis
Amarasinghe, S. L., Su, S., Dong, X., Zappia, L., Ritchie, M. E., & Gouil, Q. (2020) · Genome Biology · doi:10.1186/s13059-020-1935-5 · Cited by 2,530
An integrated map of structural variation in 2,504 human genomes
Sudmant, P. H., Rausch, T., Gardner, E. J., Handsaker, R. E., Abyzov, A., Huddleston, J., Zhang, Y., Ye, K., Jun, G., Hsi-Yang Fritz, M., et al. (2015) · Nature · doi:10.1038/nature15394 · Cited by 2,354
Self-citationMcDonald-McGinn, D. M., Sullivan, K. E., Marino, B., Philip, N., Swillen, A., Vorstman, J. A. S., Zackai, E. H., Emanuel, B. S., Vermeesch, J. R., Morrow, B. E., et al. (2015) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2015.71 · Cited by 2,236
PacBio Sequencing and its Applications
Rhoads, A., & Au, K. F. (2015) · Genomics, Proteomics & Bioinformatics · doi:10.1016/j.gpb.2015.08.002 · Cited by 2,135
Wenger, A. M., Peluso, P., Rowell, W. J., Chang, P.-C., Hall, R. J., Concepcion, G. T., Ebler, J., Fungtammasan, A., Kolesnikov, A., Olson, N. D., et al. (2019) · Nature Biotechnology · doi:10.1038/s41587-019-0217-9 · Cited by 1,841
Self-citationSchneider, V. A., Graves-Lindsay, T., Howe, K., Bouk, N., Chen, H.-C., Kitts, P. A., Murphy, T. D., Pruitt, K. D., Thibaud-Nissen, F., Albracht, D., et al. (2017) · Genome Research · doi:10.1101/gr.213611.116 · Cited by 1,193
Self-citationAshley, E. A. (2016) · Nature Reviews Genetics · doi:10.1038/nrg.2016.86 · Cited by 1,116
The Third Revolution in Sequencing Technology
van Dijk, E. L., Jaszczyszyn, Y., Naquin, D., & Thermes, C. (2018) · Trends in Genetics · doi:10.1016/j.tig.2018.05.008 · Cited by 1,057
Multi-platform discovery of haplotype-resolved structural variation in human genomes
Chaisson, M. J. P., Sanders, A. D., Zhao, X., Malhotra, A., Porubsky, D., Rausch, T., Gardner, E. J., Rodriguez, O. L., Guo, L., Collins, R. L., et al. (2019) · Nature Communications · doi:10.1038/s41467-018-08148-z · Cited by 891
Self-citationStructural variant calling: the long and the short of it
Mahmoud, M., Gobet, N., Cruz-Dávalos, D. I., Mounier, N., Dessimoz, C., & Sedlazeck, F. J. (2019) · Genome Biology · doi:10.1186/s13059-019-1828-7 · Cited by 725
Direct determination of diploid genome sequences
Weisenfeld, N. I., Kumar, V., Shah, P., Church, D. M., & Jaffe, D. B. (2017) · Genome Research · doi:10.1101/gr.214874.116 · Cited by 803
Telomere-to-telomere assembly of a complete human X chromosome
Miga, K. H., Koren, S., Rhie, A., Vollger, M. R., Gershman, A., Bzikadze, A., Brooks, S., Howe, E., Porubsky, D., Logsdon, G. A., et al. (2020) · Nature · doi:10.1038/s41586-020-2547-7 · Cited by 765
Self-citationHaplotype-resolved diverse human genomes and integrated analysis of structural variation
Ebert, P., Audano, P. A., Zhu, Q., Rodriguez-Martin, B., Porubsky, D., Bonder, M. J., Sulovari, A., Ebler, J., Zhou, W., Serra Mari, R., et al. (2021) · Science · doi:10.1126/science.abf7117 · Cited by 702
Self-citationPiercing the dark matter: bioinformatics of long-range sequencing and mapping
Sedlazeck, F. J., Lee, H., Darby, C. A., & Schatz, M. C. (2018) · Nature Reviews Genetics · doi:10.1038/s41576-018-0003-4 · Cited by 530
Characterizing the Major Structural Variant Alleles of the Human Genome
Audano, P. A., Sulovari, A., Graves-Lindsay, T. A., Cantsilieris, S., Sorensen, M., Welch, A. E., Dougherty, M. L., Nelson, B. J., Shah, A., Dutcher, S. K., et al. (2019) · Cell · doi:10.1016/j.cell.2018.12.019 · Cited by 492
Self-citationAbundant contribution of short tandem repeats to gene expression variation in humans
Gymrek, M., Willems, T., Guilmatre, A., Zeng, H., Markus, B., Georgiev, S., Daly, M. J., Price, A. L., Pritchard, J. K., Sharp, A. J., et al. (2016) · Nature Genetics · doi:10.1038/ng.3461 · Cited by 410
A complete reference genome improves analysis of human genetic variation
Aganezov, S., Yan, S. M., Soto, D. C., Kirsche, M., Zarate, S., Avdeyev, P., Taylor, D. J., Shafin, K., Shumate, A., Xiao, C., et al. (2022) · Science · doi:10.1126/science.abl3533 · Cited by 441
Self-citationA robust benchmark for detection of germline large deletions and insertions
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., et al. (2020) · Nature Biotechnology · doi:10.1038/s41587-020-0538-8 · Cited by 418
Self-citationFrom telomere to telomere: The transcriptional and epigenetic state of human repeat elements
Hoyt, S. J., Storer, J. M., Hartley, G. A., Grady, P. G. S., Gershman, A., de Lima, L. G., Limouse, C., Halabian, R., Wojenski, L., Rodriguez, M., et al. (2022) · Science · doi:10.1126/science.abk3112 · Cited by 411
Self-citationGenome graphs and the evolution of genome inference
Paten, B., Novak, A. M., Eizenga, J. M., & Garrison, E. (2017) · Genome Research · doi:10.1101/gr.214155.116 · Cited by 351
Redin, C., Brand, H., Collins, R. L., Kammin, T., Mitchell, E., Hodge, J. C., Hanscom, C., Pillalamarri, V., Seabra, C. M., Abbott, M.-A., et al. (2017) · Nature Genetics · doi:10.1038/ng.3720 · Cited by 334
Segmental duplications and their variation in a complete human genome
Vollger, M. R., Guitart, X., Dishuck, P. C., Mercuri, L., Harvey, W. T., Gershman, A., Diekhans, M., Sulovari, A., Munson, K. M., Lewis, A. P., et al. (2022) · Science · doi:10.1126/science.abj6965 · Cited by 350
Self-citationLong-read sequence assembly of the gorilla genome
Gordon, D., Huddleston, J., Chaisson, M. J. P., Hill, C. M., Kronenberg, Z. N., Munson, K. M., Malig, M., Raja, A., Fiddes, I., Hillier, L. W., et al. (2016) · Science · doi:10.1126/science.aae0344 · Cited by 333
Self-citationGenotyping structural variants in pangenome graphs using the vg toolkit
Hickey, G., Heller, D., Monlong, J., Sibbesen, J. A., Sirén, J., Eizenga, J., Dawson, E. T., Garrison, E., Novak, A. M., & Paten, B. (2020) · Genome Biology · doi:10.1186/s13059-020-1941-7 · Cited by 319
Semi-automated assembly of high-quality diploid human reference genomes
Jarvis, E. D., Formenti, G., Rhie, A., Guarracino, A., Yang, C., Wood, J., Tracey, A., Thibaud-Nissen, F., Vollger, M. R., Porubsky, D., et al. (2022) · Nature · doi:10.1038/s41586-022-05325-5 · Cited by 209
Self-citationTrost, B., Walker, S., Wang, Z., Thiruvahindrapuram, B., MacDonald, J. R., Sung, W. W. L., Pereira, S. L., Whitney, J., Chan, A. J. S., Pellecchia, G., et al. (2018) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2017.12.007 · Cited by 191
Human Genome Structural Variation Consortium, Porubsky, D., Ebert, P., Audano, P. A., Vollger, M. R., Harvey, W. T., Marijon, P., Ebler, J., Munson, K. M., Sorensen, M., et al. (2021) · Nature Biotechnology · doi:10.1038/s41587-020-0719-5 · Cited by 203
Self-citationYang, T., Liu, R., Luo, Y., Hu, S., Wang, D., Wang, C., Pandey, M. K., Ge, S., Xu, Q., Li, N., et al. (2022) · Nature Genetics · doi:10.1038/s41588-022-01172-2 · Cited by 191
Lyons, J. J. (2018) · Immunology and Allergy Clinics of North America · doi:10.1016/j.iac.2018.04.003 · Cited by 179
Long-Read DNA Sequencing: Recent Advances and Remaining Challenges
Warburton, P. E., & Sebra, R. P. (2023) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-101722-103045 · Cited by 163
The evolution and population diversity of human-specific segmental duplications
Dennis, M. Y., Harshman, L., Nelson, B. J., Penn, O., Cantsilieris, S., Huddleston, J., Antonacci, F., Penewit, K., Denman, L., Raja, A., et al. (2017) · Nature Ecology & Evolution · doi:10.1038/s41559-016-0069 · Cited by 159
Self-citationTransposable element detection from whole genome sequence data
Ewing, A. D. (2015) · Mobile DNA · doi:10.1186/s13100-015-0055-3 · Cited by 155
A comprehensive evaluation of long read error correction methods
Zhang, H., Jain, C., & Aluru, S. (2020) · BMC Genomics · doi:10.1186/s12864-020-07227-0 · Cited by 150
Recurrent de novo mutations in neurodevelopmental disorders: properties and clinical implications
Wilfert, A. B., Sulovari, A., Turner, T. N., Coe, B. P., & Eichler, E. E. (2017) · Genome Medicine · doi:10.1186/s13073-017-0498-x · Cited by 144
Self-citationChang, C.-H., & Larracuente, A. M. (2019) · Genetics · doi:10.1534/genetics.118.301765 · Cited by 141
Single-cell genomics meets human genetics
Cuomo, A. S. E., Nathan, A., Raychaudhuri, S., MacArthur, D. G., & Powell, J. E. (2023) · Nature Reviews Genetics · doi:10.1038/s41576-023-00599-5 · Cited by 124
Zhao, X., Collins, R. L., Lee, W.-P., Weber, A. M., Jun, Y., Zhu, Q., Weisburd, B., Huang, Y., Audano, P. A., Wang, H., et al. (2021) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2021.03.014 · Cited by 132
Self-citationKim, J.-H., Dilthey, A. T., Nagaraja, R., Lee, H.-S., Koren, S., Dudekula, D., Wood III, W. H., Piao, Y., Ogurtsov, A. Y., Utani, K., et al. (2018) · Nucleic Acids Research · doi:10.1093/nar/gky442 · Cited by 86
The Genetics of Intellectual Disability
Jansen, S., Vissers, L. E. L. M., & de Vries, B. B. A. (2023) · Brain Sciences · doi:10.3390/brainsci13020231 · Cited by 81
Shin, G., Grimes, S. M., Lee, H., Lau, B. T., Xia, L. C., & Ji, H. P. (2017) · Nature Communications · doi:10.1038/ncomms14291 · Cited by 54
Ayalew, W., Xiaoyun, W., Tarekegn, G. M., Tessema, T. S., Chu, M., Liang, C., Naboulsi, R., Van Damme, R., Bongcam-Rudloff, E., & Ping, Y. (2024) · BMC Genomics · doi:10.1186/s12864-024-10936-5 · Cited by 15
Liu, G. E. (2025) · Journal of Animal Science and Biotechnology · doi:10.1186/s40104-025-01294-7 · Cited by 8
Metadata
- Authors
- Chaisson, M. J. P., Huddleston, J., Dennis, M. Y., Sudmant, P. H., Malig, M., Hormozdiari, F., Antonacci, F., Surti, U., Sandstrom, R., Boitano, M., Landolin, J. M., Stamatoyannopoulos, J. A., Hunkapiller, M. W., Korlach, J., & Eichler, E. E.
- Venue
- Nature
- Published
- 2014-11-10
- Volume
- 517
- Issue
- 7536
- Pages
- 608-611
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2002438422
- Cited by
- 783
- References
- 6
- FWCI
- 49.33
- Type
- journal article
- Language
- en
- Open access
- bronze
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
