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, Liu, Jason, Yu, Keyang, Berthel, Ana, Chen, Zhanlin, Navarro, Fabio, Sun, Maxwell S, Wright, James, Chang, Justin, Cameron, Christopher JF, 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 (March 2023) The EN-TEx resource of multi-tissue personal epigenomes & variant-impact models. Cell, 186 (7). 1493-1511.e40. ISSN 0092-8674

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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.

Item Type:	Paper
Subjects:	bioinformatics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics Investigative techniques and equipment Investigative techniques and equipment > assays bioinformatics > genomics and proteomics > genetics & nucleic acid processing > epigenetics bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > epigenetics Investigative techniques and equipment > assays > genome wide association studies bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > transcription factor
CSHL Authors:	Drenkow, Jorg Danyko, Cassidy Davis, Carrie A. Scavelli, Alexandra Sedlazeck, Fritz See, Lei Hoon Werner, Jonathan Zaleski, Christopher Dobin, Alexander Gillis, Jesse Schatz, Michael C. Gingeras, Thomas R.
Communities:	CSHL labs > Gillis Lab CSHL labs > Gingeras lab CSHL labs > Schatz lab CSHL labs > Wigler lab CSHL labs > Dobin Lab CSHL Cancer Center Program CSHL Cancer Center Program > Cancer Genetics and Genomics Program CSHL Cancer Center Program > Gene Regulation and Inheritance Program
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	30 March 2023
Date Deposited:	19 Sep 2023 13:54
Last Modified:	09 Feb 2024 15:48
PMCID:	PMC10074325
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/40903

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