The EN-TEx resource of multi-tissue personal epigenomes & variant-impact models
Rozowsky, Joel Gao, Jiahao Borsari, Beatrice Yang, Yucheng T Galeev, Timur Gürsoy, Gamze Epstein, Charles B Xiong, Kun Xu, Jinrui Li, Tianxiao
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Authors
Gao, 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
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UMass Chan Affiliations
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Abstract
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.