{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T15:15:38Z","timestamp":1777043738800,"version":"3.51.4"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T00:00:00Z","timestamp":1774656000000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["62572142"],"award-info":[{"award-number":["62572142"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["62172121"],"award-info":[{"award-number":["62172121"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"2023 Shanghai Municipal Science and Technology Innovation Action Plan Special Project on Cell and Gene Therapy","award":["23J21901200"],"award-info":[{"award-number":["23J21901200"]}]},{"name":"Fundamental Research Funds for the Central Universities at Harbin Engineering University","award":["GK762026011560"],"award-info":[{"award-number":["GK762026011560"]}]},{"name":"Fundamental Research Funds for the Central Universities at Harbin Engineering University","award":["GK762026011562"],"award-info":[{"award-number":["GK762026011562"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Motivation<\/jats:title>\n                    <jats:p>Protein\u2013protein interactions (PPIs) are central to cellular functions, and predicting mutation-induced changes in binding affinity (\u0394\u0394G) remains challenging. Although existing computational methods integrate sequence- and structure-derived features and thus implicitly capture certain sequence\u2013structure relationships, they typically fuse these modalities through simple concatenation, without explicitly modeling their multidimensional and multiscale interdependencies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Here, we introduce IGMI, an interpretable graph-based model that explicitly encodes multi-level feature interactions across 1D sequences, 2D contact maps, 3D structures, and residue- and atom-level representations. By recalibrating cross-dimensional and cross-scale dependencies, IGMI enables more accurate estimation of both local and long-range mutation effects. Across multiple benchmark datasets, IGMI consistently outperforms state-of-the-art methods in accuracy, robustness, and interpretability. Macro- and micro-level analyses further reveal biologically plausible patterns, distinguishing direct interface perturbations from indirect structural reorganizations. Complementary analyses under different data splitting strategies indicate that the model learns generalizable affinity-related interaction patterns, rather than relying on split-specific information. IGMI provides a reliable and interpretable framework for modeling mutation-induced affinity changes, supporting applications in protein engineering and therapeutic design.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Availability and implementation<\/jats:title>\n                    <jats:p>IGMI is implemented in PyTorch and released under an open-source license. The full codebase, training scripts, and evaluation utilities are available at https:\/\/github.com\/ShiweiWu-545\/IGMI.git. An archival snapshot containing all source code, pre-trained weights, processed datasets, and reproducibility scripts is available on Zenodo (https:\/\/doi.org\/10.5281\/zenodo.17563574).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Contact<\/jats:title>\n                    <jats:p>fengweixing@hrbeu.edu.cn; yulei@nbic.ecnu.edu.cn; zhaochengkui@hrbeu.edu.cn<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Supplementary information<\/jats:title>\n                    <jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btag150","type":"journal-article","created":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T12:48:44Z","timestamp":1774529324000},"source":"Crossref","is-referenced-by-count":0,"title":["Enhancing mutation impact prediction in protein-protein interactions through interpretable graph-based multi-level feature interactions"],"prefix":"10.1093","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-3392-521X","authenticated-orcid":false,"given":"Shiwei","family":"Wu","sequence":"first","affiliation":[{"name":"College of Intelligent Systems Science and Engineering, Harbin Engineering University , Harbin,","place":["China"]}]},{"given":"Nan","family":"Xu","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Engineering and Technology, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University , Shanghai,","place":["China"]},{"name":"Shanghai Unicar-Therapy Bio-medicine Technology Co., Ltd , Shanghai,","place":["China"]}]},{"given":"Xiaohui","family":"Xin","sequence":"additional","affiliation":[{"name":"College of Intelligent Systems Science and Engineering, Harbin Engineering University , Harbin,","place":["China"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9928-5189","authenticated-orcid":false,"given":"Min","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Intelligent Systems Science and Engineering, Harbin Engineering University , Harbin,","place":["China"]}]},{"given":"Haoliang","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Intelligent Systems Science and Engineering, Harbin Engineering University , Harbin,","place":["China"]}]},{"given":"Hongjia","family":"Zhu","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Engineering and Technology, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University , Shanghai,","place":["China"]},{"name":"Shanghai Unicar-Therapy Bio-medicine Technology Co., Ltd , Shanghai,","place":["China"]}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2950-2560","authenticated-orcid":false,"given":"Zhenyu","family":"Wei","sequence":"additional","affiliation":[{"name":"College of Intelligent Systems Science and Engineering, Harbin Engineering University , Harbin,","place":["China"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4328-466X","authenticated-orcid":false,"given":"Chengkui","family":"Zhao","sequence":"additional","affiliation":[{"name":"College of Intelligent Systems Science and Engineering, Harbin Engineering University , Harbin,","place":["China"]},{"name":"Shanghai Unicar-Therapy Bio-medicine Technology Co., Ltd , Shanghai,","place":["China"]}]},{"given":"Lei","family":"Yu","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Engineering and Technology, Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University , Shanghai,","place":["China"]},{"name":"Shanghai Unicar-Therapy Bio-medicine Technology Co., Ltd , Shanghai,","place":["China"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6466-7918","authenticated-orcid":false,"given":"Weixing","family":"Feng","sequence":"additional","affiliation":[{"name":"College of Intelligent Systems Science and Engineering, Harbin Engineering University , Harbin,","place":["China"]}]}],"member":"286","published-online":{"date-parts":[[2026,3,27]]},"reference":[{"key":"2026042409465584400_btag150-B1","article-title":"BeAtMuSiC: prediction of changes in protein\u2013protein binding affinity on mutations","year":"2013","journal-title":"Nucleic Acids Res"},{"key":"2026042409465584400_btag150-B2","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/s41586-024-07487-w","article-title":"Accurate structure prediction of biomolecular interactions with AlphaFold 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