{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T07:32:00Z","timestamp":1772955120672,"version":"3.50.1"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:00:00Z","timestamp":1771459200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Progetti Ateneo \u2018Sapienza University of Rome\u2019","award":["RM1221815D52AB32"],"award-info":[{"award-number":["RM1221815D52AB32"]}]},{"name":"Italy Ministry of University and Research PRIN","award":["2022N3JXLA"],"award-info":[{"award-number":["2022N3JXLA"]}]},{"name":"CNR International Joint Laboratories-Thematic: Biomedical Sciences"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,2,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Motivation<\/jats:title>\n                    <jats:p>G-quadruplex-binding proteins (G4BPs) play key roles in RNA metabolism and stress response, yet their identification remains experimentally challenging. Here, we present a deep learning (DL) framework for the prediction of RNA G4BPs (RG4BPs), integrating diverse encoding strategies and neural architectures. Our best-performing model, which includes ESM-2 protein language model embeddings and consists of an LSTM architecture, achieved 86% accuracy in distinguishing RG4BPs from non-binder proteins. The application of this model to the human proteome uncovered 2160 high-confidence RG4BP candidates, many of which display intrinsically disordered regions (IDRs) and enrichment in stress granule organelles. These findings reveal a potential link between G-quadruplex recognition and cellular stress responses. To enable easy and broad access to the framework, we developed G4REP, a web server for RG4BP prediction and analysis. Overall, an effective approach to explore the RG4BPs landscape and uncover novel players in RNA regulation is provided.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability<\/jats:title>\n                    <jats:p>Source code for the G4REP Model training and evaluation is available at: https:\/\/github.com\/G4REP\/G4REPmodel and at https:\/\/doi.org\/10.5281\/zenodo.17963046. G4REP Server is hosted at: https:\/\/schubert.bio.uniroma1.it\/g4\/<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btag088","type":"journal-article","created":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T12:54:29Z","timestamp":1771505669000},"source":"Crossref","is-referenced-by-count":0,"title":["A deep learning framework for comprehensive prediction of human RNA G-quadruplex-binding proteins"],"prefix":"10.1093","volume":"42","author":[{"given":"Serena","family":"Rosignoli","sequence":"first","affiliation":[{"name":"Centre for Regenerative Medicine \u201cStefano Ferrari\u201d, Department of Life Sciences, University of Modena and Reggio Emilia , Modena 41125,","place":["Italy"]}]},{"given":"Sophie","family":"Taraglio","sequence":"additional","affiliation":[{"name":"Department of Biochemical Sciences \u201cA. Rossi Fanelli\u201d, Sapienza University of Rome , Rome 00185,","place":["Italy"]}]},{"given":"Francesco","family":"Di Luzio","sequence":"additional","affiliation":[{"name":"Department of Information Engineering, Electronics and Telecommunications, Sapienza University of Rome , Rome 00184,","place":["Italy"]}]},{"given":"Elisa","family":"Lustrino","sequence":"additional","affiliation":[{"name":"Department of Biochemical Sciences \u201cA. Rossi Fanelli\u201d, Sapienza University of Rome , Rome 00185,","place":["Italy"]}]},{"given":"Dario","family":"Marzella","sequence":"additional","affiliation":[{"name":"Medical BioSciences Department, Radboud University Medical Center , Nijmegen 6500,","place":["The Netherlands"]}]},{"given":"Arne","family":"Elofsson","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Biophysics and Science for Life Laboratory, Stockholm University , Solna 171 21,","place":["Sweden"]}]},{"given":"Massimo","family":"Panella","sequence":"additional","affiliation":[{"name":"Department of Information Engineering, Electronics and Telecommunications, Sapienza University of Rome , Rome 00184,","place":["Italy"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9078-7545","authenticated-orcid":false,"given":"Alessandro","family":"Paiardini","sequence":"additional","affiliation":[{"name":"Department of Biochemical Sciences \u201cA. 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