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As a challenging question, less attention has been given to PTM dynamics underlying cross-talk residue pairs and structural information underlying protein\u2013protein interaction (PPI) graph, limiting the progress in this PTM functional research. Here we propose a novel integrated deep neural network PPICT (Predictor for PTM Inter-protein Cross-Talk), which predicts PTM cross-talk by combining protein sequence-structure-dynamics information and structural information for PPI graph. We find that cross-talk events preferentially occur among residues with high co-evolution and high potential in allosteric regulation. To make full use of the complex associations between protein evolutionary and biophysical features, and protein pair features, a heterogeneous feature combination net is introduced in the final prediction of PPICT. The comprehensive test results show that the proposed PPICT method significantly improves the prediction performance with an AUC value of 0.869, outperforming the existing state-of-the-art methods. Additionally, the PPICT method can capture the potential PTM cross-talks involved in the functional regulatory PTMs on modifying enzymes and their catalyzed PTM substrates. Therefore, PPICT represents an effective tool for identifying PTM cross-talk between proteins at the proteome level and highlights the hints for cross-talk between different signal pathways introduced by PTMs.<\/jats:p>","DOI":"10.1093\/bib\/bbad052","type":"journal-article","created":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T01:42:00Z","timestamp":1676338920000},"source":"Crossref","is-referenced-by-count":12,"title":["PPICT: an integrated deep neural network for predicting inter-protein PTM cross-talk"],"prefix":"10.1093","volume":"24","author":[{"given":"Fei","family":"Zhu","sequence":"first","affiliation":[{"name":"School of Computer Science and Technology, Soochow University , 215006, Suzhou , China"},{"name":"Center for Systems Biology , Department of Bioinformatics, School of Biology and Basic Medical Sciences, , 215123, Suzhou , China"},{"name":"Soochow University , Department of Bioinformatics, School of Biology and Basic Medical Sciences, , 215123, Suzhou , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Deng","sequence":"additional","affiliation":[{"name":"School of Computer Science and Technology, Soochow University , 215006, Suzhou , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuhao","family":"Dai","sequence":"additional","affiliation":[{"name":"School of Computer Science and Technology, Soochow University , 215006, Suzhou , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guangyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Computer Science and Technology, Soochow University , 215006, Suzhou , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fanwang","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Chemical Biology, McMaster University , L8S 4L8, Ontario , 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