Pan-conserved segment tags identify ultra-conserved sequences across assemblies in the human pangenome

• DOI: 10.1016/j.crmeth.2023.100543
• Publication Date: 2023-08-02T14:34:53Z
• Authors: HoJoon Lee; Stephanie U. Greer; Dmitri S. Pavlichin; Bo Zhou; Alexander E. Urban; Tsachy Weissman; Hanlee P. Ji; 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; Lucinda L. Antona...; Gunjan Baid; Carl A. Baker; Anastasiya Belyaeva; Konstantinos Billis; Andrew Carroll; Pi-Chuan Chang; Sarah Cody; Daniel E. Cook; Omar E. Cornejo; Mark Diekhans; Peter Ebert; Susan Fairley; Olivier Fedrigo; Adam L. Felsenfeld; Giulio Formenti; Adam Frankish; Yan Gao; Carlos Garcia Giron; Richard E. Green; Leanne Haggerty; Kendra Hoekzema; Thibaut Hourlier; Hanlee P. Ji; Alexey Kolesnikov; Jan O. Korbel; Jennifer Kordosky; HoJoon Lee; Alexandra P. Lewis; Hugo Magalhães; Santiago Marco-Sola; Pierre Marijon; Jennifer McDaniel; Jacquelyn Mountca...; Maria Nattestad; Nathan D. Olson; Daniela Puiu; Allison A. Regier; Arang Rhie; Samuel Sacco; Ashley D. Sanders; Valerie A. Schneider; Baergen I. Schultz; Kishwar Shafin; Jouni Sirén; Michael W. Smith; Heidi J. Sofia; Ahmad N. Abou Tayoun; Françoise Thibaud...; Francesca Florian...; Justin Wagner; Jonathan M.D. Wood; Aleksey V. Zimin; Alice B. Popejoy; Guillaume Bourque; Mark J.P. 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
• Keywords: Cancer Research; pangenome; Polymorphism, Genetic; Skin Neoplasms; k-mer; Haploidy; structural variations; Article; structural polymorphism; Squamous Cell; Genetic; Neoplasms; Humans; Neoplasms, Squamous Cell; Polymorphism; Genes, Cells and Cell-Based Medicine [Topic 1]; reference genome; Conserved Sequence; pan-conserved segment

The human pangenome, a new reference sequence, addresses many limitations of the current GRCh38 reference. The first release is based on 94 high-quality haploid assemblies from individuals with diverse backgrounds. We employed a k-mer indexing strategy for comparative analysis across multiple assemblies, including the pangenome reference, GRCh38, and CHM13, a telomere-to-telomere reference assembly. Our k-mer indexing approach enabled us to identify a valuable collection of universally conserved sequences across all assemblies, referred to as "pan-conserved segment tags" (PSTs). By examining intervals between these segments, we discerned highly conserved genomic segments and those with structurally related polymorphisms. We found 60,764 polymorphic intervals with unique geo-ethnic features in the pangenome reference. In this study, we utilized ultra-conserved sequences (PSTs) to forge a link between human pangenome assemblies and reference genomes. This methodology enables the examination of any sequence of interest within the pangenome, using the reference genome as a comparative framework.