{"doi":"10.1101/635516","title":"Conserved epigenetic regulatory logic infers genes governing cell identity","abstract":"<h4>SUMMARY</h4> Determining genes orchestrating cell differentiation in development and disease remains a fundamental goal of cell biology. This study establishes a genome-wide metric based on the gene-repressive tri-methylation of histone 3 lysine 27 (H3K27me3) across hundreds of diverse cell types to identify genetic regulators of cell differentiation. We introduce a computational method, TRIAGE, that uses discordance between gene-repressive tendency and expression to identify genetic drivers of cell identity. We apply TRIAGE to millions of genome-wide single-cell transcriptomes, diverse omics platforms, and eukaryotic cells and tissue types. Using a wide range of data, we validate TRIAGE’s performance for identifying cell-type specific regulatory factors across diverse species including human, mouse, boar, bird, fish, and tunicate. Using CRISPR gene editing, we use TRIAGE to experimentally validate RNF220 as a regulator of Ciona cardiopharyngeal development and SIX3 as required for differentiation of endoderm in human pluripotent stem cells. A record of this paper’s Transparent Peer Review process is included in the Supplemental Information.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2019,"id":5943,"datarank":0.4571140533222475,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"self_citation_contribution":0.32958368660043297,"citation_network_contribution":0.12753036672181453,"self_endowment_contribution":0.32958368660043297,"citer_contribution":0.12753036672181453,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":5,"citers_with_citation_signal":5,"citers_with_endowment":5,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.0531,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2019-05-12","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":56511,"name":"Enakshi Sinniah","orcid":"0000-0002-3403-3658","position":1,"is_corresponding":false},{"id":35938,"name":"Jun Xu","orcid":"0000-0002-7140-7823","position":2,"is_corresponding":false},{"id":56512,"name":"Burcu Vitrinel","orcid":"0000-0002-5049-6572","position":3,"is_corresponding":false},{"id":56513,"name":"Michael Alexanian","orcid":"0000-0001-6224-6354","position":4,"is_corresponding":false},{"id":56514,"name":"Gaia Andreoletti","orcid":"0000-0002-0452-0009","position":5,"is_corresponding":false},{"id":56515,"name":"Sophie Shen","orcid":"0000-0002-1867-050X","position":6,"is_corresponding":false},{"id":56516,"name":"Yuliangzi Sun","orcid":"0000-0001-9785-4261","position":7,"is_corresponding":false},{"id":56517,"name":"Brad Balderson","orcid":"0000-0002-5153-6601","position":8,"is_corresponding":false},{"id":56518,"name":"Guangdun Peng","orcid":"0000-0002-8586-0637","position":10,"is_corresponding":false},{"id":56519,"name":"Naihe Jing","orcid":"0000-0003-1509-6378","position":11,"is_corresponding":false},{"id":56520,"name":"Yuliang Wang","orcid":null,"position":12,"is_corresponding":false},{"id":14693,"name":"Sharon L. 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