{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T01:12:02Z","timestamp":1771463522052,"version":"3.50.1"},"reference-count":77,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2025,3,3]],"date-time":"2025-03-03T00:00:00Z","timestamp":1740960000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Protein\u2013protein interactions (PPIs) form a complex network called \u201cinteractome\u201d that regulates many functions in the cell. In recent years, there is an increasing accumulation of evidence supporting the existence of a hyperbolic geometry underlying the network representation of complex systems such as the interactome. In particular, it has been shown that the embedding of the human Protein-Interaction Network (hPIN) in hyperbolic space (H<jats:sup>2<\/jats:sup>) captures biologically relevant information. Here we explore whether this mapping contains information that would allow us to predict the function of PPIs, more specifically interactions related to post-translational modification (PTM). We used a random forest algorithm to predict PTM-related directed PPIs, concretely, protein phosphorylation and dephosphorylation, based on hyperbolic properties and centrality measures of the hPIN mapped in H<jats:sup>2<\/jats:sup>. To evaluate the efficacy of our algorithm, we predicted PTM-related PPIs of ataxin-1, a protein which is responsible for Spinocerebellar Ataxia type 1 (SCA1). Proteomics analysis in a cellular model revealed that several of the predicted PTM-PPIs were indeed dysregulated in a SCA1-related disease network. A compact cluster composed of ataxin-1, its dysregulated PTM-PPIs and their common upstream regulators may represent critical interactions for disease pathology. Thus, our algorithm may infer phosphorylation activity on proteins through directed PPIs.<\/jats:p>","DOI":"10.1371\/journal.pone.0319084","type":"journal-article","created":{"date-parts":[[2025,3,3]],"date-time":"2025-03-03T18:37:03Z","timestamp":1741027023000},"page":"e0319084","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Prediction of protein interactions with function in protein 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