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Computational approaches are orders of magnitude cheaper and faster than experimental ones, leading to proliferation of multiple methods aimed to predict which residues belong to the interface of an interaction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We present BIPSPI, a new machine learning-based method for the prediction of partner-specific PPI sites. Contrary to most binding site prediction methods, the proposed approach takes into account a pair of interacting proteins rather than a single one in order to predict partner-specific binding sites. BIPSPI has been trained employing sequence-based and structural features from both protein partners of each complex compiled in the Protein\u2013Protein Docking Benchmark version 5.0 and in an additional set independently compiled. Also, a version trained only on sequences has been developed. The performance of our approach has been assessed by a leave-one-out cross-validation over different benchmarks, outperforming state-of-the-art methods.<\/jats:p><\/jats:sec><jats:sec><jats:title>Availability and implementation<\/jats:title><jats:p>BIPSPI web server is freely available at http:\/\/bipspi.cnb.csic.es. BIPSPI code is available at https:\/\/github.com\/bioinsilico\/BIPSPI. Docker image is available at https:\/\/hub.docker.com\/r\/bioinsilico\/bipspi\/.<\/jats:p><\/jats:sec><jats:sec><jats:title>Supplementary information<\/jats:title><jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p><\/jats:sec>","DOI":"10.1093\/bioinformatics\/bty647","type":"journal-article","created":{"date-parts":[[2018,7,18]],"date-time":"2018-07-18T17:05:03Z","timestamp":1531933503000},"page":"470-477","source":"Crossref","is-referenced-by-count":92,"title":["BIPSPI: a method for the prediction of partner-specific protein\u2013protein interfaces"],"prefix":"10.1093","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6156-3542","authenticated-orcid":false,"given":"Ruben","family":"Sanchez-Garcia","sequence":"first","affiliation":[{"name":"GN7 of the Spanish National Institute for Bioinformatics (INB), Biocomputing Unit, National Center of Biotechnology (CSIC), Instruct Image Processing Center, Madrid, Spain"}]},{"given":"C O S","family":"Sorzano","sequence":"additional","affiliation":[{"name":"GN7 of the Spanish National Institute for Bioinformatics (INB), Biocomputing Unit, National Center of Biotechnology (CSIC), Instruct Image Processing Center, Madrid, Spain"}]},{"given":"J M","family":"Carazo","sequence":"additional","affiliation":[{"name":"GN7 of the Spanish National Institute for Bioinformatics (INB), Biocomputing Unit, National Center of Biotechnology (CSIC), Instruct Image Processing Center, Madrid, Spain"}]},{"given":"Joan","family":"Segura","sequence":"additional","affiliation":[{"name":"GN7 of the Spanish National Institute for Bioinformatics (INB), Biocomputing Unit, National Center of Biotechnology (CSIC), Instruct Image Processing Center, Madrid, Spain"}]}],"member":"286","published-online":{"date-parts":[[2018,7,18]]},"reference":[{"key":"2023013107242574800_bty647-B1","doi-asserted-by":"crossref","first-page":"e29104","DOI":"10.1371\/journal.pone.0029104","article-title":"Partner-aware prediction of interacting residues in protein\u2013protein complexes from sequence data","volume":"6","author":"Ahmad","year":"2011","journal-title":"PLoS One"},{"key":"2023013107242574800_bty647-B2","doi-asserted-by":"crossref","first-page":"3389","DOI":"10.1093\/nar\/25.17.3389","article-title":"Gapped BLAST and PSI-BLAST: a new generation of protein database search programs","volume":"25","author":"Altschul","year":"1997","journal-title":"Nucleic Acids Res"},{"key":"2023013107242574800_bty647-B3","doi-asserted-by":"crossref","first-page":"D419","DOI":"10.1093\/nar\/gkm993","article-title":"Data growth and its impact on the SCOP database: new developments","volume":"36","author":"Andreeva","year":"2008","journal-title":"Nucleic Acids Res"},{"key":"2023013107242574800_bty647-B4","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1023\/A:1010933404324","article-title":"Random forests","volume":"45","author":"Breiman","year":"2001","journal-title":"Mach. 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