The EN-TEx resource of multi-tissue personal epigenomes & variant-impact models.
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Embargo End Date
ICR Authors
Authors
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
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
Document Type
Journal Article
Date
2023-03-30
Date Accepted
2023-02-10
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.
Citation
Cell, 2023, 186 (7), pp. 1493 - 1511.e40
Source Title
Cell
Publisher
CELL PRESS
ISSN
0092-8674
eISSN
1097-4172
1097-4172
1097-4172
Collections
Research Team
Functional Proteomics
Prote & Metabolomics Fac
Prote & Metabolomics Fac