PROSE: phenotype-specific network signatures from individual proteomic samples

Proteomic studies characterize the protein composition of complex biological samples. 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.