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Despite recent advancements in mass spectrometry instrumentation and computational tools, low proteome coverage and interpretability remains a challenge. To address this, we developed Proteome Support Vector Enrichment (PROSE), a fast, scalable and lightweight pipeline for scoring proteins based on orthogonal gene co-expression network matrices. PROSE utilizes simple protein lists as input, generating a standard enrichment score for all proteins, including undetected ones. In our benchmark with 7 other candidate prioritization techniques, PROSE shows high accuracy in missing protein prediction, with scores correlating strongly to corresponding gene expression data. As a further proof-of-concept, we applied PROSE to a reanalysis of the Cancer Cell Line Encyclopedia proteomics dataset, where it captures key phenotypic features, including gene dependency. We lastly demonstrated its applicability on a breast cancer clinical dataset, showing clustering by annotated molecular subtype and identification of putative drivers of triple-negative breast cancer. PROSE is available as a user-friendly Python module from https:\/\/github.com\/bwbio\/PROSE.<\/jats:p>","DOI":"10.1093\/bib\/bbad075","type":"journal-article","created":{"date-parts":[[2023,3,13]],"date-time":"2023-03-13T02:26:55Z","timestamp":1678674415000},"source":"Crossref","is-referenced-by-count":2,"title":["PROSE: phenotype-specific network signatures from individual proteomic samples"],"prefix":"10.1093","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0504-0653","authenticated-orcid":false,"given":"Bertrand Jern Han","family":"Wong","sequence":"first","affiliation":[{"name":"School of Biological Sciences, Nanyang Technological University , Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weijia","family":"Kong","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Nanyang Technological University , Singapore"},{"name":"Lee Kong Chian School of Medicine, Nanyang Technological University , Singapore"},{"name":"School of Computer Science, National University of Singapore , Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Peng","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Nanyang Technological University , Singapore"},{"name":"Lee Kong Chian School of Medicine, Nanyang Technological University , Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3863-7501","authenticated-orcid":false,"given":"Wilson Wen Bin","family":"Goh","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Nanyang Technological University , Singapore"},{"name":"Lee Kong Chian School of Medicine, Nanyang Technological University , Singapore"},{"name":"Center for Biomedical Informatics, Nanyang Technological University , 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