{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T08:45:46Z","timestamp":1765442746581,"version":"3.46.0"},"reference-count":79,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T00:00:00Z","timestamp":1765411200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Piano Nazionale di Ripresa e Resilienza","award":["Decreto Ministeriale n. 118 del 02\/03\/2023, M4C1 I. 4.1"],"award-info":[{"award-number":["Decreto Ministeriale n. 118 del 02\/03\/2023, M4C1 I. 4.1"]}]},{"name":"INSERM, the Fondation Toulouse Cancer Sant\u00e9 and Pierre Fabre Research Institute"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Entropy"],"abstract":"<jats:p>Background: Climate change, urbanization, and global mobility increase the risk of emerging infectious diseases with pandemic potential. There is a need for rapid methods that can assess their long-term effects on human health. In silico approaches are particularly suited to study processes that may manifest years later, under the assumption that perturbed biomolecular interactions underlie these outcomes. Here we focus on viral oncogenicity\u2014the ability of viruses to increase cancer risk\u2014which accounts for about 15% of global cancer cases. Methods: We characterize viruses through multilayer representations of protein\u2013protein interaction (PPI) networks reconstructed from the human interactome. Statistical analyses of topological features, combined with interpretable machine learning models, are used to distinguish oncogenic from non-oncogenic viruses and to identify proteins with potential central role in these processes. Results: Our analysis reveals clear statistical differences between the network properties of oncogenic and non-oncogenic viruses. Furthermore, the machine learning approach enables classification of virus\u2013host interaction networks and identification of relevant subsets of proteins associated with oncogenesis. Functional enrichment analysis highlights mechanisms related to viral oncogenicity, including chromatin structure and other processes linked to cancer development. Conclusions: This framework enables virus classification and highlights mechanisms underlying viral oncogenicity, providing a foundation for investigating long-term health effects of emerging pathogens.<\/jats:p>","DOI":"10.3390\/e27121248","type":"journal-article","created":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T08:39:18Z","timestamp":1765442358000},"page":"1248","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Unraveling the Network Signatures of Oncogenicity in Virus\u2013Human Protein\u2013Protein Interactions"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5631-5584","authenticated-orcid":false,"given":"Francesco","family":"Zambelli","sequence":"first","affiliation":[{"name":"Department of Physics and Astronomy \u201cGalileo Galilei\u201d, University of Padova, 35121 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7433-624X","authenticated-orcid":false,"given":"Vera","family":"Pancaldi","sequence":"additional","affiliation":[{"name":"Centre de Recherches en Canc\u00e9rologie de Toulouse (CRCT), Universit\u00e9 de Toulouse, Inserm, CNRS, 31100 Toulouse, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5158-8594","authenticated-orcid":false,"given":"Manlio","family":"De Domenico","sequence":"additional","affiliation":[{"name":"Department of Physics and Astronomy \u201cGalileo Galilei\u201d, University of Padova, 35121 Padova, Italy"},{"name":"Padua Center for Network Medicine, University of Padova, 35131 Padova, Italy"},{"name":"Istituto Nazionale di Fisica Nucleare Sezione di Padova, 35131 Padova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1086\/518281","article-title":"The Long-Term Outcomes of Human West Nile Virus Infection","volume":"44","author":"Hughes","year":"2007","journal-title":"Clin. 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