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An encyclopedia of enhancer-gene regulatory interactions in the human genome [preprint]

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العنوان: An encyclopedia of enhancer-gene regulatory interactions in the human genome [preprint]
المؤلفون: Gschwind, Andreas R, Mualim, Kristy S, Karbalayghareh, Alireza, Sheth, Maya U, Dey, Kushal K, Jagoda, Evelyn, Nurtdinov, Ramil N, Xi, Wang, Tan, Anthony S, Jones, Hank, Ma, X Rosa, Yao, David, Nasser, Joseph, Avsec, Žiga, James, Benjamin T, Shamim, Muhammad S, Durand, Neva C, Rao, Suhas S P, Mahajan, Ragini, Doughty, Benjamin R, Andreeva, Kalina, Ulirsch, Jacob C, Fan, Kaili, Perez, Elizabeth M, Nguyen, Tri C, Kelley, David R, Finucane, Hilary K, Moore, Jill E, Weng, Zhiping, Kellis, Manolis, Bassik, Michael C, Price, Alkes L, Beer, Michael A, Guigó, Roderic, Stamatoyannopoulos, John A, Lieberman Aiden, Erez, Greenleaf, William J, Leslie, Christina S, Steinmetz, Lars M, Kundaje, Anshul, Engreitz, Jesse M
المساهمون: Program in Bioinformatics and Integrative Biology
المصدر: bioRxiv : the preprint server for biology ; United States
سنة النشر: 2023
المجموعة: University of Massachusetts, Medical School: eScholarship@UMMS
مصطلحات موضوعية: Genomics, gene regulation
الوصف: This article is a preprint. Preprints are preliminary reports of work that have not been certified by peer review. ; Identifying transcriptional enhancers and their target genes is essential for understanding gene regulation and the impact of human genetic variation on disease1-6. Here we create and evaluate a resource of >13 million enhancer-gene regulatory interactions across 352 cell types and tissues, by integrating predictive models, measurements of chromatin state and 3D contacts, and largescale genetic perturbations generated by the ENCODE Consortium7. We first create a systematic benchmarking pipeline to compare predictive models, assembling a dataset of 10,411 elementgene pairs measured in CRISPR perturbation experiments, >30,000 fine-mapped eQTLs, and 569 fine-mapped GWAS variants linked to a likely causal gene. Using this framework, we develop a new predictive model, ENCODE-rE2G, that achieves state-of-the-art performance across multiple prediction tasks, demonstrating a strategy involving iterative perturbations and supervised machine learning to build increasingly accurate predictive models of enhancer regulation. Using the ENCODE-rE2G model, we build an encyclopedia of enhancer-gene regulatory interactions in the human genome, which reveals global properties of enhancer networks, identifies differences in the functions of genes that have more or less complex regulatory landscapes, and improves analyses to link noncoding variants to target genes and cell types for common, complex diseases. By interpreting the model, we find evidence that, beyond enhancer activity and 3D enhancer-promoter contacts, additional features guide enhancerpromoter communication including promoter class and enhancer-enhancer synergy. Altogether, these genome-wide maps of enhancer-gene regulatory interactions, benchmarking software, predictive models, and insights about enhancer function provide a valuable resource for future studies of gene regulation and human genetics.
نوع الوثيقة: report
اللغة: English
Relation: bioRxiv; https://doi.org/10.1101/2023.11.09.563812; Gschwind AR, Mualim KS, Karbalayghareh A, Sheth MU, Dey KK, Jagoda E, Nurtdinov RN, Xi W, Tan AS, Jones H, Ma XR, Yao D, Nasser J, Avsec Ž, James BT, Shamim MS, Durand NC, Rao SSP, Mahajan R, Doughty BR, Andreeva K, Ulirsch JC, Fan K, Perez EM, Nguyen TC, Kelley DR, Finucane HK, Moore JE, Weng Z, Kellis M, Bassik MC, Price AL, Beer MA, Guigó R, Stamatoyannopoulos JA, Lieberman Aiden E, Greenleaf WJ, Leslie CS, Steinmetz LM, Kundaje A, Engreitz JM. An encyclopedia of enhancer-gene regulatory interactions in the human genome. bioRxiv [Preprint]. 2023 Nov 13:2023.11.09.563812. doi:10.1101/2023.11.09.563812. PMID: 38014075; PMCID: PMC10680627.; http://hdl.handle.net/20.500.14038/52868; bioRxiv : the preprint server for biology
DOI: 10.1101/2023.11.09.563812
الاتاحة: https://doi.org/10.1101/2023.11.09.563812
https://hdl.handle.net/20.500.14038/52868
Rights: The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license. ; Attribution-NoDerivatives 4.0 International ; http://creativecommons.org/licenses/by-nd/4.0/
رقم الانضمام: edsbas.A2BEFF88
قاعدة البيانات: BASE
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