{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T11:44:15Z","timestamp":1753875855442,"version":"3.41.2"},"reference-count":56,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T00:00:00Z","timestamp":1745366400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001665","name":"French National Research Agency","doi-asserted-by":"publisher","award":["ANR-19-CHIA-0020"],"award-info":[{"award-number":["ANR-19-CHIA-0020"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,6,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>Accurately predicting complex protein\u2013protein interactions (PPIs) is crucial for decoding biological processes, from cellular functioning to disease mechanisms. However, experimental methods for determining PPIs are computationally expensive. Thus, attention has been recently drawn to machine learning approaches. Furthermore, insufficient effort has been made toward analyzing signed PPI networks, which capture both activating (positive) and inhibitory (negative) interactions. To accurately represent biological relationships, we present the Signed Two-Space Proximity Model (S2-SPM) for signed PPI networks, which explicitly incorporates both types of interactions, reflecting the complex regulatory mechanisms within biological systems. This is achieved by leveraging two independent latent spaces to differentiate between positive and negative interactions while representing protein similarity through proximity in these spaces. Our approach also enables the identification of archetypes representing extreme protein profiles.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>S2-SPM\u2019s superior performance in predicting the presence and sign of interactions in SPPI networks is demonstrated in link prediction tasks against relevant baseline methods. Additionally, the biological prevalence of the identified archetypes is confirmed by an enrichment analysis of Gene Ontology (GO) terms, which reveals that distinct biological tasks are associated with archetypal groups formed by both interactions. This study is also validated regarding statistical significance and sensitivity analysis, providing insights into the functional roles of different interaction types. Finally, the robustness and consistency of the extracted archetype structures are confirmed using the Bayesian Normalized Mutual Information (BNMI) metric, proving the model\u2019s reliability in capturing meaningful SPPI patterns.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability<\/jats:title>\n                  <jats:p>S2-SPM is implemented and freely available under the MIT license at https:\/\/github.com\/Nicknakis\/S2SPM.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btaf204","type":"journal-article","created":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T16:38:17Z","timestamp":1745426297000},"source":"Crossref","is-referenced-by-count":0,"title":["The signed two-space proximity model for learning representations in protein\u2013protein interaction 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91120,","place":["France"]}]},{"given":"Iakovos","family":"Evdaimon","sequence":"additional","affiliation":[{"name":"\u00c9cole Polytechnique, LIX, Institute Polytechnique de Paris , Palaiseau, 91120,","place":["France"]}]},{"given":"Michalis","family":"Vazirgiannis","sequence":"additional","affiliation":[{"name":"\u00c9cole Polytechnique, LIX, Institute Polytechnique de Paris , Palaiseau, 91120,","place":["France"]},{"name":"MBZUAI, Mohamed bin Zayed, University of Artificial Intelligence , Abu Dhabi,","place":["United Arab Emirates"]}]}],"member":"286","published-online":{"date-parts":[[2025,4,23]]},"reference":[{"key":"2025070408321937200_btaf204-B1","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1037\/h0046049","article-title":"Structural balance: a generalization of Heider\u2019s theory","volume":"63","author":"Cartwright","year":"1956","journal-title":"Psychol Rev"},{"year":"2014","author":"Chen Y, Mairal J, 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