The EN-TEx resource of multi-tissue personal epigenomes & variant-impact models
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Authors
Rozowsky, JoelGao, Jiahao
Borsari, Beatrice
Yang, Yucheng T
Galeev, Timur
Gürsoy, Gamze
Epstein, Charles B
Xiong, Kun
Xu, Jinrui
Li, Tianxiao
Liu, Jason
Yu, Keyang
Berthel, Ana
Chen, Zhanlin
Navarro, Fabio
Sun, Maxwell S
Wright, James
Chang, Justin
Cameron, Christopher J F
Shoresh, Noam
Gaskell, Elizabeth
Drenkow, Jorg
Adrian, Jessika
Aganezov, Sergey
Aguet, François
Balderrama-Gutierrez, Gabriela
Banskota, Samridhi
Corona, Guillermo Barreto
Chee, Sora
Chhetri, Surya B
Cortez Martins, Gabriel Conte
Danyko, Cassidy
Davis, Carrie A
Farid, Daniel
Farrell, Nina P
Gabdank, Idan
Gofin, Yoel
Gorkin, David U
Gu, Mengting
Hecht, Vivian
Hitz, Benjamin C
Issner, Robbyn
Jiang, Yunzhe
Kirsche, Melanie
Kong, Xiangmeng
Lam, Bonita R
Li, Shantao
Li, Bian
Li, Xiqi
Lin, Khine Zin
Luo, Ruibang
Mackiewicz, Mark
Meng, Ran
Moore, Jill E
Mudge, Jonathan
Nelson, Nicholas
Nusbaum, Chad
Popov, Ioann
Pratt, Henry E
Qiu, Yunjiang
Ramakrishnan, Srividya
Raymond, Joe
Salichos, Leonidas
Scavelli, Alexandra
Schreiber, Jacob M
Sedlazeck, Fritz J
See, Lei Hoon
Sherman, Rachel M
Shi, Xu
Shi, Minyi
Sloan, Cricket Alicia
Strattan, J Seth
Tan, Zhen
Tanaka, Forrest Y
Vlasova, Anna
Wang, Jun
Werner, Jonathan
Williams, Brian
Xu, Min
Yan, Chengfei
Yu, Lu
Zaleski, Christopher
Zhang, Jing
Ardlie, Kristin
Cherry, J Michael
Mendenhall, Eric M
Noble, William S
Weng, Zhiping
Levine, Morgan E
Dobin, Alexander
Wold, Barbara
Mortazavi, Ali
Ren, Bing
Gillis, Jesse
Myers, Richard M
Snyder, Michael P
Choudhary, Jyoti
Milosavljevic, Aleksandar
Schatz, Michael C
Bernstein, Bradley E
Guigó, Roderic
Gingeras, Thomas R
Gerstein, Mark
Student Authors
Henry PrattUMass Chan Affiliations
Morningside Graduate School of Biomedical SciencesProgram in Bioinformatics and Integrative Biology
Document Type
Journal ArticlePublication Date
2023-03-30Keywords
ENCODEGTEx
allele-specific activity
eQTLs
functional epigenomes
functional genomics
genome annotations
personal genome
predictive models
structural variants
tissue specificity
transformer model
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Show full item recordAbstract
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.Source
Rozowsky J, Gao J, Borsari B, Yang YT, Galeev T, Gürsoy G, Epstein CB, Xiong K, Xu J, Li T, Liu J, Yu K, Berthel A, Chen Z, Navarro F, Sun MS, Wright J, Chang J, Cameron CJF, Shoresh N, Gaskell E, Drenkow J, Adrian J, Aganezov S, Aguet F, Balderrama-Gutierrez G, Banskota S, Corona GB, Chee S, Chhetri SB, Cortez Martins GC, Danyko C, Davis CA, Farid D, Farrell NP, Gabdank I, Gofin Y, Gorkin DU, Gu M, Hecht V, Hitz BC, Issner R, Jiang Y, Kirsche M, Kong X, Lam BR, Li S, Li B, Li X, Lin KZ, Luo R, Mackiewicz M, Meng R, Moore JE, Mudge J, Nelson N, Nusbaum C, Popov I, Pratt HE, Qiu Y, Ramakrishnan S, Raymond J, Salichos L, Scavelli A, Schreiber JM, Sedlazeck FJ, See LH, Sherman RM, Shi X, Shi M, Sloan CA, Strattan JS, Tan Z, Tanaka FY, Vlasova A, Wang J, Werner J, Williams B, Xu M, Yan C, Yu L, Zaleski C, Zhang J, Ardlie K, Cherry JM, Mendenhall EM, Noble WS, Weng Z, Levine ME, Dobin A, Wold B, Mortazavi A, Ren B, Gillis J, Myers RM, Snyder MP, Choudhary J, Milosavljevic A, Schatz MC, Bernstein BE, Guigó R, Gingeras TR, Gerstein M. The EN-TEx resource of multi-tissue personal epigenomes & variant-impact models. Cell. 2023 Mar 30;186(7):1493-1511.e40. doi: 10.1016/j.cell.2023.02.018. PMID: 37001506; PMCID: PMC10074325.DOI
10.1016/j.cell.2023.02.018Permanent Link to this Item
http://hdl.handle.net/20.500.14038/51962PubMed ID
37001506Rights
Copyright 2023 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).; Attribution 4.0 InternationalDistribution License
http://creativecommons.org/licenses/by/4.0/ae974a485f413a2113503eed53cd6c53
10.1016/j.cell.2023.02.018
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Except where otherwise noted, this item's license is described as Copyright 2023 The Authors. Published by Elsevier Inc.
This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).