A draft human pangenome reference
Wen‐Wei Liao, Mobin Asri, Jana Ebler, Daniel Doerr, Marina Haukness, Glenn Hickey, Shuangjia Lu, Julian Lucas, Jean Monlong, Haley Abel, Silvia Buonaiuto, Xian 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 Porubskỳ, Pjotr Prins, Jonas A. Sibbesen, Jouni Sirén, Chad Tomlinson, Flavia Villani, Mitchell R. Vollger, Lucinda Antonacci-Fulton, Gunjan Baid, Carl Baker, Anastasiya Belyaeva, Konstantinos Billis, Andrew Carroll, Pi-Chuan Chang, Sarah Cody, Daniel E. Cook, Robert Cook‐Deegan, Omar E. Cornejo, Mark Diekhans, Peter Ebert, Susan Fairley, Olivier Fédrigo, Adam L. Felsenfeld, Giulio Formenti, Adam Frankish, Yan Gao, Nanibaa’ A. Garrison, Carlos García Girón, 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, HoJoon Lee, Alexandra P. Lewis, Hugo Magalhães, Santiago Marco‐Sola, Pierre Marijon, Ann M. Mc Cartney, Jennifer McDaniel, Jacquelyn Mountcastle, Maria Nattestad, Sergey Nurk, Nathan D. Olson, Alice B. Popejoy, Daniela Puiu, Mikko Rautiainen, Allison Regier, Arang Rhie, Samuel Sacco, Ashley D. Sanders, Valérie Schneider, Baergen I. Schultz, Kishwar Shafin, Michael W. Smith, Heidi J. Sofia, Ahmad Abou Tayoun, Françoise Thibaud‐Nissen, Francesca Floriana Tricomi
Abstract
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.