Towards complete and error-free genome assemblies of all vertebrate species

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt


  • Arang Rhie
  • Shane A. McCarthy
  • Olivier Fedrigo
  • Joana Damas
  • Giulio Formenti
  • Sergey Koren
  • Marcela Uliano-Silva
  • William Chow
  • Arkarachai Fungtammasan
  • Juwan Kim
  • Chul Lee
  • Byung June Ko
  • Mark Chaisson
  • Gregory L. Gedman
  • Lindsey J. Cantin
  • Francoise Thibaud-Nissen
  • Leanne Haggerty
  • Iliana Bista
  • Michelle Smith
  • Bettina Haase
  • Jacquelyn Mountcastle
  • Sylke Winkler
  • Sadye Paez
  • Jason Howard
  • Sonja C. Vernes
  • Tanya M. Lama
  • Frank Grutzner
  • Wesley C. Warren
  • Christopher N. Balakrishnan
  • Dave Burt
  • Julia M. George
  • Matthew T. Biegler
  • David Iorns
  • Andrew Digby
  • Daryl Eason
  • Bruce Robertson
  • Taylor Edwards
  • Mark Wilkinson
  • George Turner
  • Axel Meyer
  • Andreas F. Kautt
  • Paolo Franchini
  • H. William Detrich
  • Hannes Svardal
  • Maximilian Wagner
  • Gavin J.P. Naylor
  • Martin Pippel
  • Milan Malinsky
  • Mark Mooney
  • Maria Simbirsky
  • Brett T. Hannigan
  • Trevor Pesout
  • Marlys Houck
  • Ann Misuraca
  • Sarah B. Kingan
  • Richard Hall
  • Zev Kronenberg
  • Ivan Sović
  • Christopher Dunn
  • Zemin Ning
  • Alex Hastie
  • Joyce Lee
  • Siddarth Selvaraj
  • Richard E. Green
  • Nicholas H. Putnam
  • Ivo Gut
  • Jay Ghurye
  • Erik Garrison
  • Ying Sims
  • Joanna Collins
  • Sarah Pelan
  • James Torrance
  • Alan Tracey
  • Jonathan Wood
  • Robel E. Dagnew
  • Dengfeng Guan
  • Sarah E. London
  • David F. Clayton
  • Claudio V. Mello
  • Samantha R. Friedrich
  • Peter V. Lovell
  • Ekaterina Osipova
  • Farooq O. Al-Ajli
  • Simona Secomandi
  • Heebal Kim
  • Constantina Theofanopoulou
  • Michael Hiller
  • Yang Zhou
  • Robert S. Harris
  • Kateryna D. Makova
  • Paul Medvedev
  • Jinna Hoffman
  • Patrick Masterson
  • Karen Clark
  • Fergal Martin
  • Kevin Howe
  • Paul Flicek
  • Brian P. Walenz
  • Woori Kwak
  • Hiram Clawson
  • Mark Diekhans
  • Luis Nassar
  • Benedict Paten
  • Robert H. S. Kraus
  • Andrew J. Crawford
  • Byrappa Venkatesh
  • Robert W. Murphy
  • Klaus-Peter Koepfli
  • Beth Shapiro
  • Warren E. Johnson
  • Federica Di Palma
  • Tomas Marques-Bonet
  • Emma C. Teeling
  • Tandy Warnow
  • Jennifer Marshall Graves
  • Oliver A. Ryder
  • David Haussler
  • Stephen J. O’Brien
  • Jonas Korlach
  • Harris A. Lewin
  • Kerstin Howe
  • Eugene W. Myers
  • Richard Durbin
  • Adam M. Phillippy
  • Erich D. Jarvis

High-quality and complete reference genome assemblies are fundamental for the application of genomics to biology, disease, and biodiversity conservation. However, such assemblies are available for only a few non-microbial species1–4. To address this issue, the international Genome 10K (G10K) consortium5,6 has worked over a five-year period to evaluate and develop cost-effective methods for assembling highly accurate and nearly complete reference genomes. Here we present lessons learned from generating assemblies for 16 species that represent six major vertebrate lineages. 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 assembly error when not handled correctly. Our assemblies correct substantial errors, add missing sequence in some of the best historical reference genomes, and reveal biological discoveries. These include the identification of many false gene duplications, increases in gene sizes, chromosome rearrangements that are specific to lineages, a repeated independent chromosome breakpoint in bat genomes, and a canonical GC-rich pattern in protein-coding genes and their regulatory regions. Adopting these lessons, we have embarked on the Vertebrate Genomes Project (VGP), an international effort to generate high-quality, complete reference genomes for all of the roughly 70,000 extant vertebrate species and to help to enable a new era of discovery across the life sciences.

Udgave nummer7856
Sider (fra-til)737-746
Antal sider10
StatusUdgivet - 2021

Bibliografisk note

Funding Information:
Acknowledgements We thank the following persons for feedback and support: R. Johnson, E. Karlsson, K. Lindblad Toh, W. Jun, I. Korf, W. Haerty, G. Etherington, B. Clavijo, and A. Komissarov for discussions in the early stages of the project; R. Fuller for help with the G10K website maintenance, and H. Segal for help with with VGP website development; M. Linh Pham for help with initial grant writing; L. Shalmiyev for administrative help; D. Church, G. Kol, K. Baruch, O. Barad, I. Liachko, E. Muzychenko, S. Garg, and M. Kolmogorov for preliminary analyses performed on one or more genomes; K. Oliver, C. Corton and J. Skelton for data generation; E. Harry for technical support in scaff10x and Pretext; C. Mazzoni for coordinating students and training at Leibniz Institute for Zoo and Wildlife Research and Berlin Center for Genomics in Biodiversity Research; and M. Driller, C. Caswara, M. Vafadar, N. Hill, D. De Panis, A. Whibley, B. Maloney, C. Mitchell, G. Gallo, J. Gaige, K. Amoako-Boadu, M. Jose Gomez, M. Montero, D. Ratnikov, S. Brown, S. Zylka, S. Marcus, and T. Carrasco for completing training and testing the VGP pipeline by producing ordinal representative genome assemblies not described in this manuscript. We thank our company partners (listed below), NCBI, EBI, and Amazon AWS, including AWS for sponsoring sequence storage. J. Fekecs and D. Leja created the animal images, and J. Kim modified them to silhouettes. We thank them for their permission to publish. A.R., S.K., B.P.W. and A.M.P. were supported by the Intramural Research Program of the NHGRI, NIH (1ZIAHG200398). A.R. was also supported by the Korea Health Technology R&D Project through KHIDI, funded by the Ministry of Health & Welfare, Republic of Korea (HI17C2098). S.A.M., I.B. and R.D. were supported by Wellcome Trust grant WT207492; W.C., M. Smith, Z.N., Y.S., J.C., S. Pelan, J.T., A.T., J.W. and Kerstin Howe by WT206194; L.H., F.M., Kevin Howe and P. Flicek by WT108749/Z/15/Z, WT218328/B/19/Z and the European Molecular Biology Laboratory. O.F. and E.D.J. were supported by Howard Hughes Medical Institute and Rockefeller University start-up funds for this project. J.D. and H.A.L. were supported by the Robert and Rosabel Osborne Endowment. M.U.-S. received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement (750747). F.T.-N., J. Hoffman, P. Masterson and K.C. were supported by the Intramural Research Program of the NLM, NIH. C.L., B.J.K., J. Kim and H.K. were supported by the Marine Biotechnology Program of KIMST, funded by the Ministry of Ocean and Fisheries, Republic of Korea (20180430). M.C. was supported by Sloan Research Fellowship (FG-2020-12932). S.C.V. was funded by a Max Planck Research Group award from the Max Planck Society, and a Human Frontiers Science Program (HFSP) Research grant (RGP0058/2016). T.M.L., W.E.J. and the Canada lynx genome were funded by the Maine Department of Inland Fisheries & Wildlife (F11AF01099), including when W.E.J. held a National Research Council Research Associateship Award at the Walter Reed Army Institute of Research (WRAIR). C.B. was supported by the NSF (1457541 and 1456612). D.B. was funded by The University of Queensland (HFSP - RGP0030/2015). D.I. was supported by Science Exchange Inc. (Palo Alto, CA). H.W.D. was supported by NSF grants (OPP-0132032 ICEFISH 2004 Cruise, PLR-1444167 and OPP-1955368) and the Marine Science Center at Northeastern University (416). G.J.P.N. and the thorny skate genome were funded by Lenfest Ocean Program (30884). M.P. was funded by the German Federal Ministry of Education and Research (01IS18026C). M. Malinsky was supported by an EMBO fellowship (ALTF 456-2016). The following authors’ contributions were supported by the NIH: S. Selvaraj (R44HG008118); C.V.M., S.R.F., P.V.L. (R21 DC014432/DC/NIDCD); K.D.M.

Funding Information:
(R01GM130691); H.C. (5U41HG002371-19); M.D. (U41HG007234); and B.P. (R01HG010485). D.G. was supported by the National Key Research and Development Program of China (2017YFC1201201, 2018YFC0910504 and 2017YFC0907503). F.O.A. was supported by Al-Gannas Qatari Society and The Cultural Village Foundation-Katara, Doha, State of Qatar and Monash University Malaysia. C.T. was supported by The Rockefeller University. M. Hiller was supported by the LOEWE-Centre for Translational Biodiversity Genomics (TBG) funded by the Hessen State Ministry of Higher Education, Research and the Arts (HMWK). H.C. was supported by the NHGRI (5U41HG002371-19). R.H.S.K. was funded by the Max Planck Society with computational resources at the bwUniCluster and BinAC funded by the Ministry of Science, Research and the Arts Baden-Württemberg and the Universities of the State of Baden-Württemberg, Germany (bwHPC-C5). B.V. was supported by the Biomedical Research Council of A*STAR, Singapore. T.M.-B. was funded by the European Research Council under the European Union’s Horizon 2020 research and innovation programme (864203), MINECO/ FEDER, UE (BFU2017-86471-P), Unidad de Excelencia María de Maeztu, AEI (CEX2018-000792-M), a Howard Hughes International Early Career award, Obra Social “La Caixa” and Secretaria d’Universitats i Recerca and CERCA Programme del Departament d’Economia i Coneixement de la Generalitat de Catalunya (GRC 2017 SGR 880). E.C.T. was supported by the European Research Council (ERC-2012-StG311000) and an Irish Research Council Laureate Award. M.T.P.G. was supported by an ERC Consolidator Award 681396-Extinction Genomics, and a Danish National Research Foundation Center Grant (DNRF143). T.W. was supported by the NSF (1458652). J. M. Graves was supported by the Australian Research Council (CEO561477). E.W.M. was partially supported by the German Federal Ministry of Education and Research (01IS18026C). Complementary sequencing support for the Anna’s hummingbird and several genomes was provided by Pacific Biosciences, Bionano Genomics, Dovetail Genomics, Arima Genomics, Phase Genomics, 10X Genomics, NRGene, Oxford Nanopore Technologies, Illumina, and DNAnexus. All other sequencing and assembly were conducted at the Rockefeller University, Sanger Institute, and Max Planck Institute Dresden genome labs. Part of this work used the computational resources of the NIH HPC Biowulf cluster (https://hpc.nih. gov). We acknowledge funding from the Wellcome Trust (108749/Z/15/Z) and the European Molecular Biology Laboratory. We thank Le Comité Scientifique Régional du Patrimoine Naturel and Direction de l’Environnement, de l’Aménagement et du Logement, Guyanne for research approvals and export permits.

Publisher Copyright:
© 2021, The Author(s).

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