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; Jouni Sirén; Chad Tomlinson; Flavia Villani; Mitchell R. Vollger; Lucinda L. Antonacci-Fulton; Gunjan Baid; Carl A. Baker; Anastasiya Belyaeva; Konstantinos Billis; Andrew Carroll; Pi Chuan Chang; Sarah Cody; Daniel E. Cook; Robert M. Cook-Deegan; Omar E. Cornejo; Mark Diekhans; Peter Ebert; Susan Fairley; Olivier Fedrigo; Adam L. Felsenfeld; Giulio Formenti; Adam Frankish; Yan Gao; Nanibaa’ A. Garrison; Carlos Garcia Giron; Richard E. Green; Leanne Haggerty; Kendra Hoekzema; Thibaut Hourlier; Hanlee P. Ji; Eimear E. Kenny; Barbara A. Koenig; Alexey Kolesnikov; Jan O. Korbel; Jennifer Kordosky; Sergey Koren; Ho Joon Lee; Alexandra P. Lewis; Hugo Magalhães; Santiago Marco-Sola; Pierre Marijon; Ann McCartney; Jennifer McDaniel; Jacquelyn Mountcastle; Maria Nattestad; Sergey Nurk; Nathan D. Olson; Alice B. Popejoy; Daniela Puiu; Mikko Rautiainen; Allison A. Regier; Arang Rhie; Samuel Sacco; Ashley D. Sanders; Valerie A. Schneider; Baergen I. Schultz; Kishwar Shafin; Michael W. Smith; Heidi J. Sofia; Ahmad N. Abou Tayoun; Françoise Thibaud-Nissen; Francesca Floriana Tricomi; Justin Wagner; Brian Walenz; Jonathan M.D. Wood; Aleksey V. Zimin; Guillaume Bourque; Mark J.P. Chaisson; Paul Flicek; Adam M. Phillippy; Justin M. Zook; Evan E. Eichler; David Haussler; Ting Wang; Erich D. Jarvis; Karen H. Miga; Erik Garrison; Tobias Marschall; Ira M. Hall; Heng Li; Benedict Paten

doi:10.1038/s41586-023-05896-x

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 GargCristian 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, Jouni Sirén, Chad Tomlinson, Flavia Villani, Mitchell R. Vollger, Lucinda L. Antonacci-Fulton, Gunjan Baid, Carl A. Baker, Anastasiya Belyaeva, Konstantinos Billis, Andrew Carroll, Pi Chuan Chang, Sarah Cody, Daniel E. Cook, Robert M. Cook-Deegan, Omar E. Cornejo, Mark Diekhans, Peter Ebert, Susan Fairley, Olivier Fedrigo, Adam L. Felsenfeld, Giulio Formenti, Adam Frankish, Yan Gao, Nanibaa’ A. Garrison, Carlos Garcia Giron, Richard E. Green, Leanne Haggerty, Kendra Hoekzema, Thibaut Hourlier, Hanlee P. Ji, Eimear E. Kenny, Barbara A. Koenig, Alexey Kolesnikov, Jan O. Korbel, Jennifer Kordosky, Sergey Koren, Ho Joon Lee, Alexandra P. Lewis, Hugo Magalhães, Santiago Marco-Sola, Pierre Marijon, Ann McCartney, Jennifer McDaniel, Jacquelyn Mountcastle, Maria Nattestad, Sergey Nurk, Nathan D. Olson, Alice B. Popejoy, Daniela Puiu, Mikko Rautiainen, Allison A. Regier, Arang Rhie, Samuel Sacco, Ashley D. Sanders, Valerie A. Schneider, Baergen I. Schultz, Kishwar Shafin, Michael W. Smith, Heidi J. Sofia, Ahmad N. Abou Tayoun, Françoise Thibaud-Nissen, Francesca Floriana Tricomi, Justin Wagner, Brian Walenz, Jonathan M.D. Wood, Aleksey V. Zimin, Guillaume Bourque, Mark J.P. Chaisson, Paul Flicek, Adam M. Phillippy, Justin M. Zook, Evan E. Eichler, David Haussler, Ting Wang, Erich D. Jarvis, Karen H. Miga, Erik Garrison, Tobias Marschall, Ira M. Hall, Heng Li, Benedict Paten

Research output: Contribution to journal › Article › peer-review

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Abstract

Here the Human Pangenome Reference Consortium presents a first draft of the human pangenome reference. The pangenome contains 47 phased, diploid assemblies from a cohort of genetically diverse individuals¹. These assemblies cover more than 99% of the expected sequence in each genome and are more than 99% accurate at the structural and base pair levels. Based on alignments of the assemblies, we generate a draft pangenome that captures known variants and haplotypes and reveals new alleles at structurally complex loci. We also add 119 million base pairs of euchromatic polymorphic sequences and 1,115 gene duplications relative to the existing reference GRCh38. Roughly 90 million of the additional base pairs are derived from structural variation. Using our draft pangenome to analyse short-read data reduced small variant discovery errors by 34% and increased the number of structural variants detected per haplotype by 104% compared with GRCh38-based workflows, which enabled the typing of the vast majority of structural variant alleles per sample.

Original language	English
Pages (from-to)	312-324
Number of pages	13
Journal	Nature
Volume	617
Issue number	7960
DOIs	https://doi.org/10.1038/s41586-023-05896-x
State	Published - May 11 2023

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10.1038/s41586-023-05896-x

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@article{7ccf16a5d66d424687825de40ad8f6f6,

title = "A draft human pangenome reference",

abstract = "Here the Human Pangenome Reference Consortium presents a first draft of the human pangenome reference. The pangenome contains 47 phased, diploid assemblies from a cohort of genetically diverse individuals 1. These assemblies cover more than 99% of the expected sequence in each genome and are more than 99% accurate at the structural and base pair levels. Based on alignments of the assemblies, we generate a draft pangenome that captures known variants and haplotypes and reveals new alleles at structurally complex loci. We also add 119 million base pairs of euchromatic polymorphic sequences and 1,115 gene duplications relative to the existing reference GRCh38. Roughly 90 million of the additional base pairs are derived from structural variation. Using our draft pangenome to analyse short-read data reduced small variant discovery errors by 34% and increased the number of structural variants detected per haplotype by 104% compared with GRCh38-based workflows, which enabled the typing of the vast majority of structural variant alleles per sample.",

author = "Liao, {Wen Wei} and Mobin Asri and Jana Ebler and Daniel Doerr and Marina Haukness and Glenn Hickey and Shuangjia Lu and Lucas, {Julian K.} and Jean Monlong and Abel, {Haley J.} and Silvia Buonaiuto and Chang, {Xian H.} and Haoyu Cheng and Justin Chu and Vincenza Colonna and Eizenga, {Jordan M.} and Xiaowen Feng and Christian Fischer and Fulton, {Robert S.} and Shilpa Garg and Cristian Groza and Andrea Guarracino and Harvey, {William T.} and Simon Heumos and Kerstin Howe and Miten Jain and Lu, {Tsung Yu} and Charles Markello and Martin, {Fergal J.} and Mitchell, {Matthew W.} and Munson, {Katherine M.} and Mwaniki, {Moses Njagi} and Novak, {Adam M.} and Olsen, {Hugh E.} and Trevor Pesout and David Porubsky and Pjotr Prins and Sibbesen, {Jonas A.} and Jouni Sir{\'e}n and Chad Tomlinson and Flavia Villani and Vollger, {Mitchell R.} and Antonacci-Fulton, {Lucinda L.} and Gunjan Baid and Baker, {Carl A.} and Anastasiya Belyaeva and Konstantinos Billis and Andrew Carroll and Chang, {Pi Chuan} and Sarah Cody and Cook, {Daniel E.} and Cook-Deegan, {Robert M.} and Cornejo, {Omar E.} and Mark Diekhans and Peter Ebert and Susan Fairley and Olivier Fedrigo and Felsenfeld, {Adam L.} and Giulio Formenti and Adam Frankish and Yan Gao and Garrison, {Nanibaa{\textquoteright} A.} and Giron, {Carlos Garcia} and Green, {Richard E.} and Leanne Haggerty and Kendra Hoekzema and Thibaut Hourlier and Ji, {Hanlee P.} and Kenny, {Eimear E.} and Koenig, {Barbara A.} and Alexey Kolesnikov and Korbel, {Jan O.} and Jennifer Kordosky and Sergey Koren and Lee, {Ho Joon} and Lewis, {Alexandra P.} and Hugo Magalh{\~a}es and Santiago Marco-Sola and Pierre Marijon and Ann McCartney and Jennifer McDaniel and Jacquelyn Mountcastle and Maria Nattestad and Sergey Nurk and Olson, {Nathan D.} and Popejoy, {Alice B.} and Daniela Puiu and Mikko Rautiainen and Regier, {Allison A.} and Arang Rhie and Samuel Sacco and Sanders, {Ashley D.} and Schneider, {Valerie A.} and Schultz, {Baergen I.} and Kishwar Shafin and Smith, {Michael W.} and Sofia, {Heidi J.} and {Abou Tayoun}, {Ahmad N.} and Fran{\c c}oise Thibaud-Nissen and Tricomi, {Francesca Floriana} and Justin Wagner and Brian Walenz and Wood, {Jonathan M.D.} and Zimin, {Aleksey V.} and Guillaume Bourque and Chaisson, {Mark J.P.} and Paul Flicek and Phillippy, {Adam M.} and Zook, {Justin M.} and Eichler, {Evan E.} and David Haussler and Ting Wang and Jarvis, {Erich D.} and Miga, {Karen H.} and Erik Garrison and Tobias Marschall and Hall, {Ira M.} and Heng Li and Benedict Paten",

note = "Funding Information: We would like to acknowledge S. Bidwell and other members of the GenBank staff at the National Center for Biotechnology Information (NCBI; NLM/NIH) for their work to release the assemblies into GenBank. Certain commercial equipment, instruments or materials are identified to adequately specify experimental conditions or reported results. Such identification does not imply recommendation or endorsement by the National Institute of Standards and Technology nor does it imply that the equipment, instruments or materials identified are necessarily the best available for the purpose. Computational infrastructure and support were provided by the Centre for Information and Media Technology at Heinrich Heine University D{\"u}sseldorf. This work was funded in part by the National Human Genome Research Institute of the National Institutes of Health under award numbers U41HG010972, 1U01HG010973, U41HG007234, 1R01HG011274, R01HG010485, U24HG010262 U01HG010963, U24HG007497 and R01HG011649. This work was funded in part by the National Institutes of Health under award numbers U01HG010961, OT2OD033761, U24HG011853, R01-HG006677, R35-GM130151, R01HG002385, R01HG010169, U01HG01973, 5U01HG010971, R01GM123489, U24HG009081 and 1ZIAHG200398. This work was funded in part by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health. The work of F.T.-N. and V.A.S. was supported by the National Center for Biotechnology Information of the National Library of Medicine (NLM), National Institutes of Health. This work was funded in part by the USDA National Institute of Food and Agriculture, grant number 2018-67015-28199, and the National Science Foundation (NSF), grant IOS-1744309, and NSF PPoSS award number 2118709 (E.G. and P.P.). This work was funded in part by the Natural Sciences and Engineering Research Council of Canada (NSERC). G.Bourque is supported by a Canada Research Chair Tier 1 award, a FRQ-S, Distinguished Research Scholar award and by the World Premier International Research Center Initiative (WPI), MEXT, Japan. J.S. was supported by the Carlsberg Foundation. This work was funded in part by intramural funding at the National Institute of Standards and Technology. E.E.E., D.H. and E.D.J. are investigators of the Howard Hughes Medical Institute. This work was funded in part by an Oxford Nanopore Research grant (SC20130149) awarded to M. Akeson, University of California Santa Cruz. This work was funded in part by Wellcome Trust award numbers WT104947/Z/14/Z, WT222155/Z/20/Z and WT108749/Z/15/Z. This work was funded in part by a Juan de la Cierva fellowship grant (IJC2020-045916-I) funded by MCIN/AEI/ 10.13039/501100011033 and by the European Union NextGenerationEU/PRTR. This work was funded in part by the Novo Nordisk Foundation (NNF21OC0069089). S.H. acknowledges funding from the Central Innovation Programme (ZIM) for SMEs of the Federal Ministry for Economic Affairs and Energy of Germany. This work was supported by the BMBF-funded de.NBI Cloud within the German Network for Bioinformatics Infrastructure (de.NBI) (031A532B, 031A533A, 031A533B, 031A534A, 031A535A, 031A537A, 031A537B, 031A537C, 031A537D and 031A538A). This work was funded in part by the German Federal Ministry of Education and Research (BMBF) (031L0184A) and the European Commission, Innovative training network (ITN) (956229). W.-W.L. was supported in part by the Government Scholarship to Study Abroad (GSSA) from the Ministry of Education of Taiwan. Funding Information: We would like to acknowledge S. Bidwell and other members of the GenBank staff at the National Center for Biotechnology Information (NCBI; NLM/NIH) for their work to release the assemblies into GenBank. Certain commercial equipment, instruments or materials are identified to adequately specify experimental conditions or reported results. Such identification does not imply recommendation or endorsement by the National Institute of Standards and Technology nor does it imply that the equipment, instruments or materials identified are necessarily the best available for the purpose. Computational infrastructure and support were provided by the Centre for Information and Media Technology at Heinrich Heine University D{\"u}sseldorf. This work was funded in part by the National Human Genome Research Institute of the National Institutes of Health under award numbers U41HG010972, 1U01HG010973, U41HG007234, 1R01HG011274, R01HG010485, U24HG010262 U01HG010963, U24HG007497 and R01HG011649. Publisher Copyright: {\textcopyright} 2023, The Author(s).",

year = "2023",

month = may,

day = "11",

doi = "10.1038/s41586-023-05896-x",

language = "English",

volume = "617",

pages = "312--324",

journal = "Nature",

issn = "0028-0836",

number = "7960",

}

Liao, WW, Asri, M, Ebler, J, Doerr, D, Haukness, M, Hickey, G, Lu, S, Lucas, JK, Monlong, J, Abel, HJ, Buonaiuto, S, Chang, XH, Cheng, H, Chu, J, Colonna, V, Eizenga, JM, Feng, X, Fischer, C, Fulton, RS, Garg, S, Groza, C, Guarracino, A, Harvey, WT, Heumos, S, Howe, K, Jain, M, Lu, TY, Markello, C, Martin, FJ, Mitchell, MW, Munson, KM, Mwaniki, MN, Novak, AM, Olsen, HE, Pesout, T, Porubsky, D, Prins, P, Sibbesen, JA, Sirén, J, Tomlinson, C, Villani, F, Vollger, MR, Antonacci-Fulton, LL, Baid, G, Baker, CA, Belyaeva, A, Billis, K, Carroll, A, Chang, PC, Cody, S, Cook, DE, Cook-Deegan, RM, Cornejo, OE, Diekhans, M, Ebert, P, Fairley, S, Fedrigo, O, Felsenfeld, AL, Formenti, G, Frankish, A, Gao, Y, Garrison, NA, Giron, CG, Green, RE, Haggerty, L, Hoekzema, K, Hourlier, T, Ji, HP, Kenny, EE, Koenig, BA, Kolesnikov, A, Korbel, JO, Kordosky, J, Koren, S, Lee, HJ, Lewis, AP, Magalhães, H, Marco-Sola, S, Marijon, P, McCartney, A, McDaniel, J, Mountcastle, J, Nattestad, M, Nurk, S, Olson, ND, Popejoy, AB, Puiu, D, Rautiainen, M, Regier, AA, Rhie, A, Sacco, S, Sanders, AD, Schneider, VA, Schultz, BI, Shafin, K, Smith, MW, Sofia, HJ, Abou Tayoun, AN, Thibaud-Nissen, F, Tricomi, FF, Wagner, J, Walenz, B, Wood, JMD, Zimin, AV, Bourque, G, Chaisson, MJP, Flicek, P, Phillippy, AM, Zook, JM, Eichler, EE, Haussler, D, Wang, T, Jarvis, ED, Miga, KH, Garrison, E, Marschall, T, Hall, IM, Li, H & Paten, B 2023, 'A draft human pangenome reference', Nature, vol. 617, no. 7960, pp. 312-324. https://doi.org/10.1038/s41586-023-05896-x

TY - JOUR

T1 - A draft human pangenome reference

AU - Liao, Wen Wei

AU - Asri, Mobin

AU - Ebler, Jana

AU - Doerr, Daniel

AU - Haukness, Marina

AU - Hickey, Glenn

AU - Lu, Shuangjia

AU - Lucas, Julian K.

AU - Monlong, Jean

AU - Abel, Haley J.

AU - Buonaiuto, Silvia

AU - Chang, Xian H.

AU - Cheng, Haoyu

AU - Chu, Justin

AU - Colonna, Vincenza

AU - Eizenga, Jordan M.

AU - Feng, Xiaowen

AU - Fischer, Christian

AU - Fulton, Robert S.

AU - Garg, Shilpa

AU - Groza, Cristian

AU - Guarracino, Andrea

AU - Harvey, William T.

AU - Heumos, Simon

AU - Howe, Kerstin

AU - Jain, Miten

AU - Lu, Tsung Yu

AU - Markello, Charles

AU - Martin, Fergal J.

AU - Mitchell, Matthew W.

AU - Munson, Katherine M.

AU - Mwaniki, Moses Njagi

AU - Novak, Adam M.

AU - Olsen, Hugh E.

AU - Pesout, Trevor

AU - Porubsky, David

AU - Prins, Pjotr

AU - Sibbesen, Jonas A.

AU - Sirén, Jouni

AU - Tomlinson, Chad

AU - Villani, Flavia

AU - Vollger, Mitchell R.

AU - Antonacci-Fulton, Lucinda L.

AU - Baid, Gunjan

AU - Baker, Carl A.

AU - Belyaeva, Anastasiya

AU - Billis, Konstantinos

AU - Carroll, Andrew

AU - Chang, Pi Chuan

AU - Cody, Sarah

AU - Cook, Daniel E.

AU - Cook-Deegan, Robert M.

AU - Cornejo, Omar E.

AU - Diekhans, Mark

AU - Ebert, Peter

AU - Fairley, Susan

AU - Fedrigo, Olivier

AU - Felsenfeld, Adam L.

AU - Formenti, Giulio

AU - Frankish, Adam

AU - Gao, Yan

AU - Garrison, Nanibaa’ A.

AU - Giron, Carlos Garcia

AU - Green, Richard E.

AU - Haggerty, Leanne

AU - Hoekzema, Kendra

AU - Hourlier, Thibaut

AU - Ji, Hanlee P.

AU - Kenny, Eimear E.

AU - Koenig, Barbara A.

AU - Kolesnikov, Alexey

AU - Korbel, Jan O.

AU - Kordosky, Jennifer

AU - Koren, Sergey

AU - Lee, Ho Joon

AU - Lewis, Alexandra P.

AU - Magalhães, Hugo

AU - Marco-Sola, Santiago

AU - Marijon, Pierre

AU - McCartney, Ann

AU - McDaniel, Jennifer

AU - Mountcastle, Jacquelyn

AU - Nattestad, Maria

AU - Nurk, Sergey

AU - Olson, Nathan D.

AU - Popejoy, Alice B.

AU - Puiu, Daniela

AU - Rautiainen, Mikko

AU - Regier, Allison A.

AU - Rhie, Arang

AU - Sacco, Samuel

AU - Sanders, Ashley D.

AU - Schneider, Valerie A.

AU - Schultz, Baergen I.

AU - Shafin, Kishwar

AU - Smith, Michael W.

AU - Sofia, Heidi J.

AU - Abou Tayoun, Ahmad N.

AU - Thibaud-Nissen, Françoise

AU - Tricomi, Francesca Floriana

AU - Wagner, Justin

AU - Walenz, Brian

AU - Wood, Jonathan M.D.

AU - Zimin, Aleksey V.

AU - Bourque, Guillaume

AU - Chaisson, Mark J.P.

AU - Flicek, Paul

AU - Phillippy, Adam M.

AU - Zook, Justin M.

AU - Eichler, Evan E.

AU - Haussler, David

AU - Wang, Ting

AU - Jarvis, Erich D.

AU - Miga, Karen H.

AU - Garrison, Erik

AU - Marschall, Tobias

AU - Hall, Ira M.

AU - Li, Heng

AU - Paten, Benedict

N1 - Funding Information: We would like to acknowledge S. Bidwell and other members of the GenBank staff at the National Center for Biotechnology Information (NCBI; NLM/NIH) for their work to release the assemblies into GenBank. Certain commercial equipment, instruments or materials are identified to adequately specify experimental conditions or reported results. Such identification does not imply recommendation or endorsement by the National Institute of Standards and Technology nor does it imply that the equipment, instruments or materials identified are necessarily the best available for the purpose. Computational infrastructure and support were provided by the Centre for Information and Media Technology at Heinrich Heine University Düsseldorf. This work was funded in part by the National Human Genome Research Institute of the National Institutes of Health under award numbers U41HG010972, 1U01HG010973, U41HG007234, 1R01HG011274, R01HG010485, U24HG010262 U01HG010963, U24HG007497 and R01HG011649. This work was funded in part by the National Institutes of Health under award numbers U01HG010961, OT2OD033761, U24HG011853, R01-HG006677, R35-GM130151, R01HG002385, R01HG010169, U01HG01973, 5U01HG010971, R01GM123489, U24HG009081 and 1ZIAHG200398. This work was funded in part by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health. The work of F.T.-N. and V.A.S. was supported by the National Center for Biotechnology Information of the National Library of Medicine (NLM), National Institutes of Health. This work was funded in part by the USDA National Institute of Food and Agriculture, grant number 2018-67015-28199, and the National Science Foundation (NSF), grant IOS-1744309, and NSF PPoSS award number 2118709 (E.G. and P.P.). This work was funded in part by the Natural Sciences and Engineering Research Council of Canada (NSERC). G.Bourque is supported by a Canada Research Chair Tier 1 award, a FRQ-S, Distinguished Research Scholar award and by the World Premier International Research Center Initiative (WPI), MEXT, Japan. J.S. was supported by the Carlsberg Foundation. This work was funded in part by intramural funding at the National Institute of Standards and Technology. E.E.E., D.H. and E.D.J. are investigators of the Howard Hughes Medical Institute. This work was funded in part by an Oxford Nanopore Research grant (SC20130149) awarded to M. Akeson, University of California Santa Cruz. This work was funded in part by Wellcome Trust award numbers WT104947/Z/14/Z, WT222155/Z/20/Z and WT108749/Z/15/Z. This work was funded in part by a Juan de la Cierva fellowship grant (IJC2020-045916-I) funded by MCIN/AEI/ 10.13039/501100011033 and by the European Union NextGenerationEU/PRTR. This work was funded in part by the Novo Nordisk Foundation (NNF21OC0069089). S.H. acknowledges funding from the Central Innovation Programme (ZIM) for SMEs of the Federal Ministry for Economic Affairs and Energy of Germany. This work was supported by the BMBF-funded de.NBI Cloud within the German Network for Bioinformatics Infrastructure (de.NBI) (031A532B, 031A533A, 031A533B, 031A534A, 031A535A, 031A537A, 031A537B, 031A537C, 031A537D and 031A538A). This work was funded in part by the German Federal Ministry of Education and Research (BMBF) (031L0184A) and the European Commission, Innovative training network (ITN) (956229). W.-W.L. was supported in part by the Government Scholarship to Study Abroad (GSSA) from the Ministry of Education of Taiwan. Funding Information: We would like to acknowledge S. Bidwell and other members of the GenBank staff at the National Center for Biotechnology Information (NCBI; NLM/NIH) for their work to release the assemblies into GenBank. Certain commercial equipment, instruments or materials are identified to adequately specify experimental conditions or reported results. Such identification does not imply recommendation or endorsement by the National Institute of Standards and Technology nor does it imply that the equipment, instruments or materials identified are necessarily the best available for the purpose. Computational infrastructure and support were provided by the Centre for Information and Media Technology at Heinrich Heine University Düsseldorf. This work was funded in part by the National Human Genome Research Institute of the National Institutes of Health under award numbers U41HG010972, 1U01HG010973, U41HG007234, 1R01HG011274, R01HG010485, U24HG010262 U01HG010963, U24HG007497 and R01HG011649. Publisher Copyright: © 2023, The Author(s).

PY - 2023/5/11

Y1 - 2023/5/11

N2 - Here the Human Pangenome Reference Consortium presents a first draft of the human pangenome reference. The pangenome contains 47 phased, diploid assemblies from a cohort of genetically diverse individuals 1. These assemblies cover more than 99% of the expected sequence in each genome and are more than 99% accurate at the structural and base pair levels. Based on alignments of the assemblies, we generate a draft pangenome that captures known variants and haplotypes and reveals new alleles at structurally complex loci. We also add 119 million base pairs of euchromatic polymorphic sequences and 1,115 gene duplications relative to the existing reference GRCh38. Roughly 90 million of the additional base pairs are derived from structural variation. Using our draft pangenome to analyse short-read data reduced small variant discovery errors by 34% and increased the number of structural variants detected per haplotype by 104% compared with GRCh38-based workflows, which enabled the typing of the vast majority of structural variant alleles per sample.

AB - Here the Human Pangenome Reference Consortium presents a first draft of the human pangenome reference. The pangenome contains 47 phased, diploid assemblies from a cohort of genetically diverse individuals 1. These assemblies cover more than 99% of the expected sequence in each genome and are more than 99% accurate at the structural and base pair levels. Based on alignments of the assemblies, we generate a draft pangenome that captures known variants and haplotypes and reveals new alleles at structurally complex loci. We also add 119 million base pairs of euchromatic polymorphic sequences and 1,115 gene duplications relative to the existing reference GRCh38. Roughly 90 million of the additional base pairs are derived from structural variation. Using our draft pangenome to analyse short-read data reduced small variant discovery errors by 34% and increased the number of structural variants detected per haplotype by 104% compared with GRCh38-based workflows, which enabled the typing of the vast majority of structural variant alleles per sample.

UR - http://www.scopus.com/inward/record.url?scp=85158007304&partnerID=8YFLogxK

U2 - 10.1038/s41586-023-05896-x

DO - 10.1038/s41586-023-05896-x

M3 - Article

C2 - 37165242

AN - SCOPUS:85158007304

SN - 0028-0836

VL - 617

SP - 312

EP - 324

JO - Nature

JF - Nature

IS - 7960

ER -

A draft human pangenome reference

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