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

Human Pangenome Reference Consortium

doi:10.1016/j.crmeth.2023.100543

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

Human Pangenome Reference Consortium

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

2 Scopus citations

Abstract

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.

Original language	English
Article number	100543
Journal	Cell Reports Methods
Volume	3
Issue number	8
DOIs	https://doi.org/10.1016/j.crmeth.2023.100543
State	Published - Aug 28 2023

Keywords

CP: Genetics
k-mer
pan-conserved segment
pangenome
reference genome
structural polymorphism
structural variations

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10.1016/j.crmeth.2023.100543

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@article{d66053583e9b4ed9877511036845c76b,

title = "Pan-conserved segment tags identify ultra-conserved sequences across assemblies in the human pangenome",

abstract = "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.",

keywords = "CP: Genetics, k-mer, pan-conserved segment, pangenome, reference genome, structural polymorphism, structural variations",

author = "{Human Pangenome Reference Consortium} and Lee, {Ho Joon} and Greer, {Stephanie U.} and Pavlichin, {Dmitri S.} and Bo Zhou and Urban, {Alexander E.} and Tsachy Weissman and 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 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 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 Giron, {Carlos Garcia} and Green, {Richard E.} and Leanne Haggerty and Kendra Hoekzema and Thibaut Hourlier and Ji, {Hanlee P.} and Alexey Kolesnikov and Korbel, {Jan O.} and Jennifer Kordosky and Lewis, {Alexandra P.} and Hugo Magalh{\~a}es and Santiago Marco-Sola and Pierre Marijon and Jennifer McDaniel and Jacquelyn Mountcastle and Maria Nattestad and Olson, {Nathan D.} and Daniela Puiu 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 Jouni Sir{\'e}n 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 Wood, {Jonathan M.D.} and Zimin, {Aleksey V.} and Popejoy, {Alice B.} 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 Jarvis, {Erich D.} and Miga, {Karen H.} and Ting Wang and Erik Garrison and Tobias Marschall and Ira Hall and Heng Li and Benedict Paten",

note = "Publisher Copyright: {\textcopyright} 2023 The Authors",

year = "2023",

month = aug,

day = "28",

doi = "10.1016/j.crmeth.2023.100543",

language = "English",

volume = "3",

journal = "Cell Reports Methods",

issn = "2667-2375",

number = "8",

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TY - JOUR

T1 - Pan-conserved segment tags identify ultra-conserved sequences across assemblies in the human pangenome

AU - Human Pangenome Reference Consortium

AU - Lee, Ho Joon

AU - Greer, Stephanie U.

AU - Pavlichin, Dmitri S.

AU - Zhou, Bo

AU - Urban, Alexander E.

AU - Weissman, Tsachy

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 - 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 - 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 - Giron, Carlos Garcia

AU - Green, Richard E.

AU - Haggerty, Leanne

AU - Hoekzema, Kendra

AU - Hourlier, Thibaut

AU - Ji, Hanlee P.

AU - Kolesnikov, Alexey

AU - Korbel, Jan O.

AU - Kordosky, Jennifer

AU - Lewis, Alexandra P.

AU - Magalhães, Hugo

AU - Marco-Sola, Santiago

AU - Marijon, Pierre

AU - McDaniel, Jennifer

AU - Mountcastle, Jacquelyn

AU - Nattestad, Maria

AU - Olson, Nathan D.

AU - Puiu, Daniela

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 - Sirén, Jouni

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 - Wood, Jonathan M.D.

AU - Zimin, Aleksey V.

AU - Popejoy, Alice B.

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 - Jarvis, Erich D.

AU - Miga, Karen H.

AU - Wang, Ting

AU - Garrison, Erik

AU - Marschall, Tobias

AU - Hall, Ira

AU - Li, Heng

AU - Paten, Benedict

PY - 2023/8/28

Y1 - 2023/8/28

N2 - 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.

AB - 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.

KW - CP: Genetics

KW - k-mer

KW - pan-conserved segment

KW - pangenome

KW - reference genome

KW - structural polymorphism

KW - structural variations

UR - http://www.scopus.com/inward/record.url?scp=85169761251&partnerID=8YFLogxK

U2 - 10.1016/j.crmeth.2023.100543

DO - 10.1016/j.crmeth.2023.100543

M3 - Article

C2 - 37671027

AN - SCOPUS:85169761251

SN - 2667-2375

VL - 3

JO - Cell Reports Methods

JF - Cell Reports Methods

IS - 8

M1 - 100543

ER -

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

Abstract

Keywords

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