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ChIP-X Enrichment Analysis 3 (ChEA3) is a transcription factor enrichment analysis tool that ranks TFs associated with user-submitted gene sets. The ChEA3 background database contains a collection of gene set libraries generated from multiple sources including TF\u2013gene co-expression from RNA-seq studies, TF\u2013target associations from ChIP-seq experiments, and TF\u2013gene co-occurrence computed from crowd-submitted gene lists. Enrichment results from these distinct sources are integrated to generate a composite rank that improves the prediction of the correct upstream TF compared to ranks produced by individual libraries. We compare ChEA3 with existing TF prediction tools and show that ChEA3 performs better. By integrating the ChEA3 libraries, we illuminate general transcription factor properties such as whether the TF behaves as an activator or a repressor. The ChEA3 web-server is available from https:\/\/amp.pharm.mssm.edu\/ChEA3.<\/jats:p>","DOI":"10.1093\/nar\/gkz446","type":"journal-article","created":{"date-parts":[[2019,5,9]],"date-time":"2019-05-09T19:21:10Z","timestamp":1557429670000},"page":"W212-W224","source":"Crossref","is-referenced-by-count":996,"title":["ChEA3: transcription factor enrichment analysis by orthogonal omics integration"],"prefix":"10.1093","volume":"47","author":[{"given":"Alexandra B","family":"Keenan","sequence":"first","affiliation":[{"name":"Department of Pharmacological Sciences, Mount Sinai Center for Bioinformatics, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1603, New York, NY 10029, USA"}]},{"given":"Denis","family":"Torre","sequence":"additional","affiliation":[{"name":"Department of Pharmacological Sciences, Mount Sinai Center for Bioinformatics, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1603, New York, NY 10029, USA"}]},{"given":"Alexander","family":"Lachmann","sequence":"additional","affiliation":[{"name":"Department of Pharmacological Sciences, Mount Sinai Center for Bioinformatics, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1603, New York, NY 10029, USA"}]},{"given":"Ariel K","family":"Leong","sequence":"additional","affiliation":[{"name":"Department of Pharmacological Sciences, Mount Sinai Center for Bioinformatics, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1603, New York, NY 10029, USA"}]},{"given":"Megan L","family":"Wojciechowicz","sequence":"additional","affiliation":[{"name":"Department of Pharmacological Sciences, Mount Sinai Center for Bioinformatics, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1603, New York, NY 10029, USA"}]},{"given":"Vivian","family":"Utti","sequence":"additional","affiliation":[{"name":"Department of Pharmacological Sciences, Mount Sinai Center for Bioinformatics, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1603, New York, NY 10029, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2755-2097","authenticated-orcid":false,"given":"Kathleen M","family":"Jagodnik","sequence":"additional","affiliation":[{"name":"Department of Pharmacological Sciences, Mount Sinai Center for Bioinformatics, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1603, New York, NY 10029, USA"}]},{"given":"Eryk","family":"Kropiwnicki","sequence":"additional","affiliation":[{"name":"Department of Pharmacological Sciences, Mount Sinai Center for Bioinformatics, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1603, New York, NY 10029, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1415-1286","authenticated-orcid":false,"given":"Zichen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacological Sciences, Mount Sinai Center for Bioinformatics, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, Box 1603, New York, NY 10029, USA"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6904-1017","authenticated-orcid":false,"given":"Avi","family":"Ma\u2019ayan","sequence":"additional","affiliation":[{"name":"Department of Pharmacological Sciences, Mount Sinai Center for Bioinformatics, Icahn School of Medicine at Mount Sinai, One Gustave L. 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