{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T20:34:31Z","timestamp":1772138071149,"version":"3.50.1"},"reference-count":15,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T00:00:00Z","timestamp":1732060800000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100013060","name":"European Molecular Biology Laboratory","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013060","id-type":"DOI","asserted-by":"publisher"}]},{"name":"German Federal Ministry of Education and Research"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,11,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Summary<\/jats:title>\n                    <jats:p>The inference of kinase activity from phosphoproteomics data can point to causal mechanisms driving signalling processes and potential drug targets. Identifying the kinases whose change in activity explains the observed phosphorylation profiles, however, remains challenging, and constrained by the manually curated knowledge of kinase\u2013substrate associations. Recently, experimentally determined substrate sequence specificities of human kinases have become available, but robust methods to exploit this new data for kinase activity inference are still missing. We present PhosX, a method to estimate differential kinase activity from phosphoproteomics data that combines state-of-the-art statistics in enrichment analysis with kinases\u2019 substrate sequence specificity information. Using a large phosphoproteomics dataset with known differentially regulated kinases we show that our method identifies upregulated and downregulated kinases by only relying on the input phosphopeptides\u2019 sequences and intensity changes. We find that PhosX outperforms the currently available approach for the same task, and performs better or similarly to state-of-the-art methods that rely on previously known kinase\u2013substrate associations. We therefore recommend its use for data-driven kinase activity inference.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and implementation<\/jats:title>\n                    <jats:p>PhosX is implemented in Python, open-source under the Apache-2.0 licence, and distributed on the Python Package Index. The code is available on GitHub (https:\/\/github.com\/alussana\/phosx).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btae697","type":"journal-article","created":{"date-parts":[[2024,11,15]],"date-time":"2024-11-15T07:24:50Z","timestamp":1731655490000},"source":"Crossref","is-referenced-by-count":3,"title":["PhosX: data-driven kinase activity inference from phosphoproteomics experiments"],"prefix":"10.1093","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4733-0934","authenticated-orcid":false,"given":"Alessandro","family":"Lussana","sequence":"first","affiliation":[{"name":"European Bioinformatics Institute, European Molecular Biology Laboratory, Wellcome Genome Campus , Hinxton CB10 1SD,","place":["United Kingdom"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9710-1865","authenticated-orcid":false,"given":"Sophia","family":"M\u00fcller-Dott","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Heidelberg University Hospital, Institute for Computational Biomedicine, Heidelberg University , Heidelberg 69120,","place":["Germany"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8552-8976","authenticated-orcid":false,"given":"Julio","family":"Saez-Rodriguez","sequence":"additional","affiliation":[{"name":"European Bioinformatics Institute, European Molecular Biology Laboratory, Wellcome Genome Campus , Hinxton CB10 1SD,","place":["United Kingdom"]},{"name":"Faculty of Medicine and Heidelberg University Hospital, Institute for Computational Biomedicine, Heidelberg University , Heidelberg 69120,","place":["Germany"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8294-2995","authenticated-orcid":false,"given":"Evangelia","family":"Petsalaki","sequence":"additional","affiliation":[{"name":"European Bioinformatics Institute, European Molecular Biology Laboratory, Wellcome Genome Campus , Hinxton CB10 1SD,","place":["United 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