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Kinase Enrichment Analysis 3 (KEA3) is a webserver application that infers overrepresentation of upstream kinases whose putative substrates are in a user-inputted list of proteins. KEA3 can be applied to analyze data from phosphoproteomics and proteomics studies to predict the upstream kinases responsible for observed differential phosphorylations. The KEA3 background database contains measured and predicted kinase-substrate interactions (KSI),\u00a0kinase-protein interactions (KPI), and interactions supported by co-expression and co-occurrence data. To benchmark the performance of KEA3, we examined whether KEA3 can predict the perturbed kinase from single-kinase perturbation followed by gene expression experiments, and phosphoproteomics data collected from kinase-targeting small molecules. We show that integrating KSIs and KPIs across data sources to produce a composite ranking improves the recovery of the expected kinase. The KEA3 webserver is available at https:\/\/maayanlab.cloud\/kea3.<\/jats:p>","DOI":"10.1093\/nar\/gkab359","type":"journal-article","created":{"date-parts":[[2021,4,23]],"date-time":"2021-04-23T00:47:22Z","timestamp":1619138842000},"page":"W304-W316","source":"Crossref","is-referenced-by-count":143,"title":["KEA3: improved kinase enrichment analysis via data integration"],"prefix":"10.1093","volume":"49","author":[{"given":"Maxim V","family":"Kuleshov","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":"Zhuorui","family":"Xie","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":"Alexandra B K","family":"London","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":"Janice","family":"Yang","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\/0000-0003-4836-0518","authenticated-orcid":false,"given":"John\u00a0Erol","family":"Evangelista","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\/0000-0002-1982-7652","authenticated-orcid":false,"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":"Ingrid","family":"Shu","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":"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"}]},{"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. Levy Place, Box 1603, New York, NY 10029, USA"}]}],"member":"286","published-online":{"date-parts":[[2021,5,21]]},"reference":[{"key":"2021070812084589700_B1","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1016\/S0021-9258(18)71184-8","article-title":"The enzymatic phosphorylation of proteins","volume":"211","author":"Burnett","year":"1954","journal-title":"J. Biol. 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