New Results
A Draft Human Pangenome Reference
View ORCID ProfileWen-Wei Liao, Mobin Asri, Jana Ebler, Daniel Doerr, Marina Haukness, View ORCID ProfileGlenn Hickey, View ORCID ProfileShuangjia Lu, Julian K. Lucas, View ORCID ProfileJean Monlong, Haley J. Abel, Silvia Buonaiuto, View ORCID ProfileXian H. Chang, Haoyu Cheng, Justin Chu, Vincenza Colonna, View ORCID ProfileJordan M. Eizenga, Xiaowen Feng, Christian Fischer, Robert S. Fulton, Shilpa Garg, Cristian Groza, Andrea Guarracino, William T Harvey, Simon Heumos, Kerstin Howe, Miten Jain, Tsung-Yu Lu, View ORCID ProfileCharles Markello, View ORCID ProfileFergal J. Martin, Matthew W. Mitchell, View ORCID ProfileKatherine M. Munson, Moses Njagi Mwaniki, View ORCID ProfileAdam M. Novak, View ORCID ProfileHugh E. Olsen, View ORCID ProfileTrevor Pesout, View ORCID ProfileDavid Porubsky, View ORCID ProfilePjotr Prins, View ORCID ProfileJonas A. Sibbesen, Chad Tomlinson, View ORCID ProfileFlavia Villani, View ORCID ProfileMitchell R. Vollger, Human Pangenome Reference Consortium, View ORCID ProfileGuillaume Bourque, View ORCID ProfileMark JP Chaisson, View ORCID ProfilePaul Flicek, Adam M. Phillippy, Justin M. Zook, View ORCID ProfileEvan E. Eichler, View ORCID ProfileDavid Haussler, Erich D. Jarvis, View ORCID ProfileKaren H. Miga, Ting Wang, View ORCID ProfileErik Garrison, Tobias Marschall, View ORCID ProfileIra Hall, View ORCID ProfileHeng Li, View ORCID ProfileBenedict Paten
doi: https://doi.org/10.1101/2022.07.09.499321
Wen-Wei Liao
1McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO 63108, USA
2Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
3Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA
Mobin Asri
4UC Santa Cruz Genomics Institute, University of California, Santa Cruz, 1156 High St, Santa Cruz, CA, USA
Jana Ebler
5Institute for Medical Biometry and Bioinformatics, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
Daniel Doerr
5Institute for Medical Biometry and Bioinformatics, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
Marina Haukness
4UC Santa Cruz Genomics Institute, University of California, Santa Cruz, 1156 High St, Santa Cruz, CA, USA
Glenn Hickey
4UC Santa Cruz Genomics Institute, University of California, Santa Cruz, 1156 High St, Santa Cruz, CA, USA
Shuangjia Lu
3Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA
Julian K. Lucas
4UC Santa Cruz Genomics Institute, University of California, Santa Cruz, 1156 High St, Santa Cruz, CA, USA
Jean Monlong
4UC Santa Cruz Genomics Institute, University of California, Santa Cruz, 1156 High St, Santa Cruz, CA, USA
Haley J. Abel
6Division of Oncology, Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
Silvia Buonaiuto
7Institute of Genetics and Biophysics, National Research Council, Naples 80111, Italy
Xian H. Chang
4UC Santa Cruz Genomics Institute, University of California, Santa Cruz, 1156 High St, Santa Cruz, CA, USA
Haoyu Cheng
8Department of Data Sciences, Dana-Farber Cancer Institute, Boston, MA 02215, USA
9Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02215, USA
Justin Chu
8Department of Data Sciences, Dana-Farber Cancer Institute, Boston, MA 02215, USA
Vincenza Colonna
7Institute of Genetics and Biophysics, National Research Council, Naples 80111, Italy
10Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, TN 38163, USA
Jordan M. Eizenga
4UC Santa Cruz Genomics Institute, University of California, Santa Cruz, 1156 High St, Santa Cruz, CA, USA
Xiaowen Feng
8Department of Data Sciences, Dana-Farber Cancer Institute, Boston, MA 02215, USA
9Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02215, USA
Christian Fischer
10Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, TN 38163, USA
Robert S. Fulton
1McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO 63108, USA
Shilpa Garg
11Department of Biology, University of Copenhagen, Denmark
Cristian Groza
12Quantitative Life Sciences, McGill University, Montreal, Québec H3A 0C7, Canada
Andrea Guarracino
13Genomics Research Centre, Human Technopole, Milan 20157, Italy
William T Harvey
14Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA
Simon Heumos
15Quantitative Biology Center (QBiC), University of Tübingen, Tübingen 72076, Germany
16Biomedical Data Science, Department of Computer Science, University of Tübingen, Tübingen 72076, Germany
Kerstin Howe
17Tree of Life, Wellcome Sanger Institute, Hinxton, Cambridge, CB10 1SA, UK
Miten Jain
18Northeastern University, Boston, MA 02115, USA
Tsung-Yu Lu
19University of Southern California, Quantitative and Computational Biology, Los Angeles, CA, USA
Charles Markello
4UC Santa Cruz Genomics Institute, University of California, Santa Cruz, 1156 High St, Santa Cruz, CA, USA
Fergal J. Martin
20European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Cambridge, CB10 1SD, UK
Matthew W. Mitchell
21Coriell Institute for Medical Research, Camden, NJ 08103, USA
Katherine M. Munson
14Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA
Moses Njagi Mwaniki
22Department of Computer Science, University of Pisa, Pisa 56127, Italy
Adam M. Novak
4UC Santa Cruz Genomics Institute, University of California, Santa Cruz, 1156 High St, Santa Cruz, CA, USA
Hugh E. Olsen
4UC Santa Cruz Genomics Institute, University of California, Santa Cruz, 1156 High St, Santa Cruz, CA, USA
Trevor Pesout
4UC Santa Cruz Genomics Institute, University of California, Santa Cruz, 1156 High St, Santa Cruz, CA, USA
David Porubsky
14Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA
Pjotr Prins
10Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, TN 38163, USA
Jonas A. Sibbesen
23Center for Health Data Science, University of Copenhagen, Denmark
Chad Tomlinson
1McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO 63108, USA
Flavia Villani
10Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, TN 38163, USA
Mitchell R. Vollger
14Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA
24Division of Medical Genetics, University of Washington School of Medicine, Seattle, WA 98195, USA
Guillaume Bourque
25Department of Human Genetics, McGill University, Montreal, Québec H3A 0C7, Canada
26Canadian Center for Computational Genomics, McGill University, Montreal, Québec H3A 0G1, Canada
27Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto University, Kyoto 606-8501, Japan
Mark JP Chaisson
19University of Southern California, Quantitative and Computational Biology, Los Angeles, CA, USA
Paul Flicek
20European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Cambridge, CB10 1SD, UK
Adam M. Phillippy
28Genome Informatics Section, Computational and Statistical Genomics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA
Justin M. Zook
29Material Measurement Laboratory, National Institute of Standards and Technology, Gaithersburg, MD 20877, USA
Evan E. Eichler
14Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA
30Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA
David Haussler
4UC Santa Cruz Genomics Institute, University of California, Santa Cruz, 1156 High St, Santa Cruz, CA, USA
30Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA
Erich D. Jarvis
31The Rockefeller University, New York, NY 10065, USA
30Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA
Karen H. Miga
4UC Santa Cruz Genomics Institute, University of California, Santa Cruz, 1156 High St, Santa Cruz, CA, USA
Ting Wang
32Department of Genetics, Washington University School of Medicine, St. Louis, MO 63110, USA
Erik Garrison
10Department of Genetics, Genomics and Informatics, University of Tennessee Health Science Center, Memphis, TN 38163, USA
Tobias Marschall
5Institute for Medical Biometry and Bioinformatics, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
Ira Hall
3Department of Genetics, Yale University School of Medicine, New Haven, CT 06510, USA
Heng Li
8Department of Data Sciences, Dana-Farber Cancer Institute, Boston, MA 02215, USA
9Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02215, USA
Benedict Paten
4UC Santa Cruz Genomics Institute, University of California, Santa Cruz, 1156 High St, Santa Cruz, CA, USA
Abstract
The Human Pangenome Reference Consortium (HPRC) presents a first draft human pangenome reference. The pangenome contains 47 phased, diploid assemblies from a cohort of genetically diverse individuals. These assemblies cover more than 99% of the expected sequence and are more than 99% accurate at the structural and base-pair levels. Based on alignments of the assemblies, we generated a draft pangenome that captures known variants and haplotypes, reveals novel alleles at structurally complex loci, and adds 119 million base pairs of euchromatic polymorphic sequence and 1,529 gene duplications relative to the existing reference, GRCh38. Roughly 90 million of the additional base pairs derive from structural variation. Using our draft pangenome to analyze short-read data reduces errors when discovering small variants by 34% and boosts the detected structural variants per haplotype by 104% compared to GRCh38-based workflows, and by 34% compared to using previous diversity sets of genome assemblies.
Competing Interest Statement
The authors have declared no competing interest.
Copyright
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
Posted July 09, 2022.
A Draft Human Pangenome Reference
Wen-Wei Liao, Mobin Asri, Jana Ebler, Daniel Doerr, Marina Haukness, Glenn Hickey, Shuangjia Lu, Julian K. Lucas, Jean Monlong, Haley J. Abel, Silvia Buonaiuto, Xian H. Chang, Haoyu Cheng, Justin Chu, Vincenza Colonna, Jordan M. Eizenga, Xiaowen Feng, Christian Fischer, Robert S. Fulton, Shilpa Garg, Cristian Groza, Andrea Guarracino, William T Harvey, Simon Heumos, Kerstin Howe, Miten Jain, Tsung-Yu Lu, Charles Markello, Fergal J. Martin, Matthew W. Mitchell, Katherine M. Munson, Moses Njagi Mwaniki, Adam M. Novak, Hugh E. Olsen, Trevor Pesout, David Porubsky, Pjotr Prins, Jonas A. Sibbesen, Chad Tomlinson, Flavia Villani, Mitchell R. Vollger, Human Pangenome Reference Consortium, Guillaume Bourque, Mark JP Chaisson, Paul Flicek, Adam M. Phillippy, Justin M. Zook, Evan E. Eichler, David Haussler, Erich D. Jarvis, Karen H. Miga, Ting Wang, Erik Garrison, Tobias Marschall, Ira Hall, Heng Li, Benedict Paten
bioRxiv 2022.07.09.499321; doi: https://doi.org/10.1101/2022.07.09.499321
A Draft Human Pangenome Reference
Wen-Wei Liao, Mobin Asri, Jana Ebler, Daniel Doerr, Marina Haukness, Glenn Hickey, Shuangjia Lu, Julian K. Lucas, Jean Monlong, Haley J. Abel, Silvia Buonaiuto, Xian H. Chang, Haoyu Cheng, Justin Chu, Vincenza Colonna, Jordan M. Eizenga, Xiaowen Feng, Christian Fischer, Robert S. Fulton, Shilpa Garg, Cristian Groza, Andrea Guarracino, William T Harvey, Simon Heumos, Kerstin Howe, Miten Jain, Tsung-Yu Lu, Charles Markello, Fergal J. Martin, Matthew W. Mitchell, Katherine M. Munson, Moses Njagi Mwaniki, Adam M. Novak, Hugh E. Olsen, Trevor Pesout, David Porubsky, Pjotr Prins, Jonas A. Sibbesen, Chad Tomlinson, Flavia Villani, Mitchell R. Vollger, Human Pangenome Reference Consortium, Guillaume Bourque, Mark JP Chaisson, Paul Flicek, Adam M. Phillippy, Justin M. Zook, Evan E. Eichler, David Haussler, Erich D. Jarvis, Karen H. Miga, Ting Wang, Erik Garrison, Tobias Marschall, Ira Hall, Heng Li, Benedict Paten
bioRxiv 2022.07.09.499321; doi: https://doi.org/10.1101/2022.07.09.499321
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