Show simple item record

dc.contributor.authorGschwind, Andreas R
dc.contributor.authorMualim, Kristy S
dc.contributor.authorKarbalayghareh, Alireza
dc.contributor.authorSheth, Maya U
dc.contributor.authorDey, Kushal K
dc.contributor.authorJagoda, Evelyn
dc.contributor.authorNurtdinov, Ramil N
dc.contributor.authorXi, Wang
dc.contributor.authorTan, Anthony S
dc.contributor.authorJones, Hank
dc.contributor.authorMa, X Rosa
dc.contributor.authorYao, David
dc.contributor.authorNasser, Joseph
dc.contributor.authorAvsec, Žiga
dc.contributor.authorJames, Benjamin T
dc.contributor.authorShamim, Muhammad S
dc.contributor.authorDurand, Neva C
dc.contributor.authorRao, Suhas S P
dc.contributor.authorMahajan, Ragini
dc.contributor.authorDoughty, Benjamin R
dc.contributor.authorAndreeva, Kalina
dc.contributor.authorUlirsch, Jacob C
dc.contributor.authorFan, Kaili
dc.contributor.authorPerez, Elizabeth M
dc.contributor.authorNguyen, Tri C
dc.contributor.authorKelley, David R
dc.contributor.authorFinucane, Hilary K
dc.contributor.authorMoore, Jill E
dc.contributor.authorWeng, Zhiping
dc.contributor.authorKellis, Manolis
dc.contributor.authorBassik, Michael C
dc.contributor.authorPrice, Alkes L
dc.contributor.authorBeer, Michael A
dc.contributor.authorGuigó, Roderic
dc.contributor.authorStamatoyannopoulos, John A
dc.contributor.authorLieberman Aiden, Erez
dc.contributor.authorGreenleaf, William J
dc.contributor.authorLeslie, Christina S
dc.contributor.authorSteinmetz, Lars M
dc.contributor.authorKundaje, Anshul
dc.contributor.authorEngreitz, Jesse M
dc.date.accessioned2023-12-15T16:41:53Z
dc.date.available2023-12-15T16:41:53Z
dc.date.issued2023-11-13
dc.identifier.citationGschwind 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.en_US
dc.identifier.doi10.1101/2023.11.09.563812en_US
dc.identifier.pmid38014075
dc.identifier.urihttp://hdl.handle.net/20.500.14038/52868
dc.descriptionThis article is a preprint. Preprints are preliminary reports of work that have not been certified by peer review.en_US
dc.description.abstractIdentifying 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.en_US
dc.language.isoenen_US
dc.relation.ispartofbioRxiven_US
dc.relation.urlhttps://doi.org/10.1101/2023.11.09.563812en_US
dc.rightsThe 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.en_US
dc.rightsAttribution-NoDerivatives 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nd/4.0/*
dc.subjectGenomicsen_US
dc.subjectgene regulationen_US
dc.titleAn encyclopedia of enhancer-gene regulatory interactions in the human genome [preprint]en_US
dc.typePreprinten_US
dc.source.journaltitlebioRxiv : the preprint server for biology
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.identifier.journalbioRxiv : the preprint server for biology
refterms.dateFOA2023-12-15T16:41:54Z
dc.contributor.departmentProgram in Bioinformatics and Integrative Biologyen_US


Files in this item

Thumbnail
Name:
2023.11.09.563812v1.full.pdf
Size:
2.865Mb
Format:
PDF

This item appears in the following Collection(s)

Show simple item record

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.
Except where otherwise noted, this item's license is described as 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.