The EN-TEx resource of multi-tissue personal epigenomes & variant-impact models.
ENCODE
GTEx
allele-specific activity
eQTLs
functional epigenomes
functional genomics
genome annotations
personal genome
predictive models
structural variants
tissue specificity
transformer model
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
30 03 2023
30 03 2023
Historique:
received:
03
04
2022
revised:
16
10
2022
accepted:
10
02
2023
pmc-release:
30
03
2024
medline:
4
4
2023
entrez:
31
3
2023
pubmed:
1
4
2023
Statut:
ppublish
Résumé
Understanding how genetic variants impact molecular phenotypes is a key goal of functional genomics, currently hindered by reliance on a single haploid reference genome. Here, we present the EN-TEx resource of 1,635 open-access datasets from four donors (∼30 tissues × ∼15 assays). The datasets are mapped to matched, diploid genomes with long-read phasing and structural variants, instantiating a catalog of >1 million allele-specific loci. These loci exhibit coordinated activity along haplotypes and are less conserved than corresponding, non-allele-specific ones. Surprisingly, a deep-learning transformer model can predict the allele-specific activity based only on local nucleotide-sequence context, highlighting the importance of transcription-factor-binding motifs particularly sensitive to variants. Furthermore, combining EN-TEx with existing genome annotations reveals strong associations between allele-specific and GWAS loci. It also enables models for transferring known eQTLs to difficult-to-profile tissues (e.g., from skin to heart). Overall, EN-TEx provides rich data and generalizable models for more accurate personal functional genomics.
Identifiants
pubmed: 37001506
pii: S0092-8674(23)00161-7
doi: 10.1016/j.cell.2023.02.018
pmc: PMC10074325
mid: NIHMS1885972
pii:
doi:
Types de publication
Journal Article
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1493-1511.e40Subventions
Organisme : NHGRI NIH HHS
ID : R01 HG009318
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH101814
Pays : United States
Organisme : NHGRI NIH HHS
ID : U54 HG007004
Pays : United States
Organisme : NHGRI NIH HHS
ID : U54 HG006991
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA253481
Pays : United States
Organisme : NHGRI NIH HHS
ID : U24 HG006620
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH113005
Pays : United States
Organisme : NHGRI NIH HHS
ID : U24 HG009397
Pays : United States
Organisme : NHGRI NIH HHS
ID : UM1 HG009442
Pays : United States
Organisme : NLM NIH HHS
ID : R01 LM012736
Pays : United States
Organisme : NHGRI NIH HHS
ID : U24 HG009446
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA045508
Pays : United States
Organisme : NHGRI NIH HHS
ID : U24 HG009649
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests Z.W. co-founded and serves as a scientific advisor for Rgenta Inc. B.E.B. declares outside interests in Fulcrum Therapeutics, HiFiBio, Arsenal Biosciences, Cell Signaling Technologies, Chroma Medicine, and Design Pharmaceuticals. M.G. is on the advisory board for HypaHub, Inc. and Elysium Health.
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