Towards complete and error-free genome assemblies of all vertebrate species
Open accessPreprint — published as 10.1038/s41586-021-03451-0 · Paper page
Abstract
High-quality and complete reference genome assemblies are fundamental for the application of genomics to biology, disease, and biodiversity conservation. However, such assemblies are only available for a few non-microbial species 1–4 . To address this issue, the international Genome 10K (G10K) consortium 5,6 has worked over a five-year period to evaluate and develop cost-effective methods for assembling the most accurate and complete reference genomes to date. Here we summarize these developments, introduce a set of quality standards, and present lessons learned from sequencing and assembling 16 species representing major vertebrate lineages (mammals, birds, reptiles, amphibians, teleost fishes and cartilaginous fishes). We confirm that long-read sequencing technologies are essential for maximizing genome quality and that unresolved complex repeats and haplotype heterozygosity are major sources of error in assemblies. Our new assemblies identify and correct substantial errors in some of the best historical reference genomes. Adopting these lessons, we have embarked on the Vertebrate Genomes Project (VGP), an effort to generate high-quality, complete reference genomes for all ~70,000 extant vertebrate species and help enable a new era of discovery across the life sciences.
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The Vertebrate Genomes Project, Genome 10K, and Earth BioGenome Project aim to release thousands of new, high-quality genome assemblies over the next decade.
“The Vertebrate Genomes Project38 led by the Genome 10K39 and the Earth BioGenome Project40, among others, aim to release thousands of new, high-quality genome assemblies over the next decade.”
From Progressive Cactus is a multiple-genome aligner for the thousand-genome era (2020) · cites this paper as [38]
As the average assembly becomes ever more complete and accurate, the value of such a reference-free approach grows.
“As the average assembly becomes ever more complete and accurate38, the value of such a reference-free approach grows.”
From Progressive Cactus is a multiple-genome aligner for the thousand-genome era (2020) · cites this paper as [38]
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- Authors
- Rhie, A., McCarthy, S. A., Fedrigo, O., Damas, J., Formenti, G., Koren, S., Uliano-Silva, M., Chow, W., Fungtammasan, A., Gedman, G. L., Cantin, L. J., Thibaud-Nissen, F., Haggerty, L., Lee, C., Ko, B. J., Kim, J., Bista, I., Smith, M., Haase, B., Mountcastle, J., Winkler, S., Paez, S., Howard, J., Vernes, S. C., Lama, T. M., Grutzner, F., Warren, W. C., Balakrishnan, C., Burt, D., George, J. M., Biegler, M., Iorns, D., Digby, A., Eason, D., Edwards, T., Wilkinson, M., Turner, G., Meyer, A., Kautt, A. F., Franchini, P., Detrich, H. W., Svardal, H., Wagner, M., Naylor, G. J. P., Pippel, M., Malinsky, M., Mooney, M., Simbirsky, M., Hannigan, B. T., Pesout, T., Houck, M., Misuraca, A., Kingan, S. B., Hall, R., Kronenberg, Z., Korlach, J., Sović, I., Dunn, C., Ning, Z., Hastie, A., Lee, J., Selvaraj, S., Green, R. E., Putnam, N. H., Ghurye, J., Garrison, E., Sims, Y., Collins, J., Pelan, S., Torrance, J., Tracey, A., Wood, J., Guan, D., London, S. E., Clayton, D. F., Mello, C. V., Friedrich, S. R., Lovell, P. V., Osipova, E., Al-Ajli, F. O., Secomandi, S., Kim, H., Theofanopoulou, C., Zhou, Y., Harris, R. S., Makova, K. D., Medvedev, P., Hoffman, J., Masterson, P., Clark, K., Martin, F., Howe, K., Flicek, P., Walenz, B. P., Kwak, W., Clawson, H., Diekhans, M., Nassar, L., Paten, B., Kraus, R. H. S., Lewin, H., Crawford, A. J., Gilbert, M. T. P., Zhang, G., Venkatesh, B., Murphy, R. W., Koepfli, K.-P., Shapiro, B., Johnson, W. E., Di Palma, F., Margues-Bonet, T., Teeling, E. C., Warnow, T., Graves, J. M., Ryder, O. A., Hausler, D., O’Brien, S. J., Howe, K., Myers, E. W., Durbin, R., Phillippy, A. M., & Jarvis, E. D.
- Affiliations
- National Institutes of Health (US)
- University of Cambridge (GB)
- Rockefeller University (US)
- University of California, Davis (US)
- Wellcome Sanger Institute (GB)
- DNAnexus (United States) (US)
- European Bioinformatics Institute (GB)
- Seoul National University (KR)
- Max Planck Institute of Molecular Cell Biology and Genetics (DE)
- University of St Andrews (GB)
- University of Massachusetts Amherst (US)
- University of Missouri (US)
- East Carolina University (US)
- Clemson University (US)
- Department of Conservation (NZ)
- University of Arizona (US)
- Natural History Museum (GB)
- Bangor University (GB)
- University of Konstanz (DE)
- Harvard University (US)
- Northeastern University (US)
- Naturalis Biodiversity Center (NL)
- University of Graz (AT)
- Florida Museum of Natural History (US)
- Center for Systems Biology Dresden (DE)
- University of Basel (CH)
- University of California, Santa Cruz (US)
- Zoological Society of San Diego (US)
- Pacific Biosciences (United States) (US)
- BioNano Genomics (United States) (US)
- Arima Genomics (United States) (US)
- Dovetail Genomics (United States) (US)
- Harbin Institute of Technology (CN)
- University of Chicago (US)
- Oregon Health & Science University (US)
- Max Planck Institute for the Physics of Complex Systems (DE)
- Monash University Malaysia (MY)
- University of Milan (IT)
- BGI Group (China) (CN)
- Pennsylvania State University (US)
- Institute of the Environment (US)
- Universidad de Los Andes (CO)
- University of Copenhagen (DK)
- Agency for Science, Technology and Research (SG)
- Royal Ontario Museum (CA)
- Smithsonian Conservation Biology Institute (US)
- Howard Hughes Medical Institute (US)
- Smithsonian Institution (US)
- University College Dublin (IE)
- University of Illinois Urbana-Champaign (US)
- La Trobe University (AU)
- ITMO University (RU)
- Corresponding author
- Howe, Kevin
- Howe, Kerstin
- Myers, Eugene W.
- Durbin, Richard
- Phillippy, Adam M.
- Jarvis, Erich D.
- ORCID
- Rhie, Arang
- McCarthy, Shane A.
- Fedrigo, Olivier
- Damas, Joana
- Formenti, Giulio
- Koren, Sergey
- Uliano-Silva, Marcela
- Chow, William
- Fungtammasan, Arkarachai
- Gedman, Gregory L.
- Cantin, Lindsey J.
- Thibaud-Nissen, Francoise
- Haggerty, Leanne
- Lee, Chul
- Ko, Byung June
- Kim, Juwan
- Bista, Iliana
- Smith, Michelle
- Haase, Bettina
- Mountcastle, Jacquelyn
- Winkler, Sylke
- Paez, Sadye
- Howard, Jason
- Vernes, Sonja C.
- Lama, Tanya M.
- Grutzner, Frank
- Warren, Wesley C.
- Balakrishnan, Christopher
- Burt, Dave
- George, Julia M.
- Digby, Andrew
- Edwards, Taylor
- Wilkinson, Mark
- Turner, George
- Meyer, Axel
- Kautt, Andreas F.
- Franchini, Paolo
- Detrich, H William
- Svardal, Hannes
- Wagner, Maximilian
- Naylor, Gavin J.P.
- Pippel, Martin
- Malinsky, Milan
- Hannigan, Brett T.
- Pesout, Trevor
- Houck, Marlys
- Misuraca, Ann
- Kingan, Sarah B.
- Hall, Richard
- Kronenberg, Zev
- Korlach, Jonas
- Sović, Ivan
- Dunn, Christopher
- Ning, Zemin
- Hastie, Alex
- Lee, Joyce
- Green, Richard E.
- Putnam, Nicholas H.
- Ghurye, Jay
- Garrison, Erik
- Sims, Ying
- Collins, Joanna
- Pelan, Sarah
- Torrance, James
- Tracey, Alan
- Wood, Jonathan
- Guan, Dengfeng
- London, Sarah E.
- Clayton, David F.
- Mello, Claudio V.
- Friedrich, Samantha R.
- Lovell, Peter V.
- Osipova, Ekaterina
- Al-Ajli, Farooq O.
- Secomandi, Simona
- Kim, Heebal
- Theofanopoulou, Constantina
- Zhou, Yang
- Makova, Kateryna D.
- Medvedev, Paul
- Masterson, Patrick
- Clark, Karen
- Martin, Fergal
- Howe, Kevin
- Flicek, Paul
- Walenz, Brian P.
- Kwak, Woori
- Clawson, Hiram
- Diekhans, Mark
- Nassar, Luis
- Paten, Benedict
- Kraus, Robert H.S.
- Lewin, Harris
- Crawford, Andrew J.
- Gilbert, M. Thomas P.
- Zhang, Guojie
- Venkatesh, Byrappa
- Murphy, Robert W.
- Koepfli, Klaus-Peter
- Shapiro, Beth
- Johnson, Warren E.
- Teeling, Emma C.
- Warnow, Tandy
- Graves, Jennifer Marshall
- Ryder, Oliver A.
- Hausler, David
- O’Brien, Stephen J.
- Howe, Kerstin
- Myers, Eugene W.
- Durbin, Richard
- Phillippy, Adam M.
- Jarvis, Erich D.
- Venue
- Nature
- Publisher
- openRxiv
- Published
- 2020-05-23
- Volume
- 592
- Issue
- 7856
- Pages
- 737-746
- ISSN
- 0028-0836 (ISSN-L)
- PMC
- PMC8081667
- OpenAlex
- W3159728495
- Cited by
- 3,097
- References
- 5
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- 134.98
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- journal article
- Language
- en
- Open access
- hybrid
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- cc-by
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- Funders
- National Science Foundation (1457541, 0132032, 1458652, 1444167, 1456612)
- Villum Fonden (00025900)
- Wellcome Trust (R01HG010485, 108749/Z/15/Z, WT207492, 207492/Z/17/Z, 207492/A/17/Z, WT206194, WT108749, WT218328/B/19/Z, /Z/15/Z, WT108749/Z/15/Z, 108749)
- Oxford Nanopore Technologies
- European Molecular Biology Laboratory
- UK Research and Innovation (MR/T021985/1)
- Centres de Recerca de Catalunya (GRC 2017 SGR 880)
- European Commission (864203, 750747, HORIZON2020, 681396)
- National Research Foundation (DNRF143)
- Deutsche Forschungsgemeinschaft (418083601)
- Danmarks Grundforskningsfond (DNRF143)
- Monash University
- University of Queensland
- Irish Research Council
- Bundesministerium für Bildung und Forschung (01IS18026C)
- Generalitat de Catalunya (2017-SGR, BFU2017-86471-P, CEX2018-000792-M, GRC 2017 SGR 880, 864203, 681396)
- Hessisches Ministerium für Wissenschaft und Kunst
- Korea Health Industry Development Institute (HI17C2098)
- Max-Planck-Gesellschaft (BFU2017-86471-P)
- Monash University Malaysia
- Korea Institute of Marine Science and Technology promotion (20180430)
- Leibniz-Institut für Zoo- und Wildtierforschung
- National Institutes of Health (WT108749/Z/15/Z)
- Directorate for Biological Sciences (1458652, 1456612, 1457541)
- Directorate for Geosciences (2324998, 1955368, 1444167, 0132032)
- Biotechnology and Biological Sciences Research Council (BBS/E/T/000PR9817, BBS/E/T/000PR9818, BBS/E/T/000PR9819)
- Australian Research Council (BFU2017-86471-P, 681396, CEX2018-000792-M, GRC 2017 SGR 880, 864203)
- Leibniz-Gemeinschaft
- Agencia Estatal de Investigación (864203, 681396, #CEX2018-000792-M, GRC 2017 SGR 880, BFU2017-86471-P)
- National Key Research and Development Program of China (2017YFC0907503, 2017YFC1201201, 2018YFC0910504)
- Biomedical Research Council
- National Human Genome Research Institute (R44HG008118, U41HG002371, R01HG010485, U41HG007234, U24HG007234, ZIAHG200398)
- National Institute on Deafness and Other Communication Disorders (R21DC014432, DC014432)
- National Institute of General Medical Sciences (R01GM130691)
- U.S. National Library of Medicine (ZIHLM200888)
- Walter Reed Army Institute of Research
- FP7 Ideas: European Research Council (311000)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Phylogenetic Studies
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Keywords
- long-read sequencing, gene duplication, chromosomal rearrangements, bat genome, reference genome
- MeSH terms
- Animals, Birds, Haplotypes, Sex Chromosomes, Vertebrates, Gene Library, Sequence Alignment, Genome, Sequence Analysis, DNA, Genomics, Genome, Mitochondrial, Molecular Sequence Annotation, High-Throughput Nucleotide Sequencing, Genome Size
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