Complex assembly and activity states as multifaceted protein attributes explaining phenotypic variability.

ABSTRACT: The state of a cell depends not only on protein abundance, but also on the biochemical and cellular activities of proteins, which are largely invisible to abundance profiling alone. Here, we introduce a multi-omics framework that infers context-specific protein activities from transcriptomic, phosphoproteomic, and protein correlation-based protein-protein interaction data, integrating modality-specific algorithms via network diffusion. Applying it to a panel of phenotypically diverse HeLa cell lines, whose genetic drift provides a natural perturbation system, we make three findings. First, physical separation of monomeric and assembled protein fractions by protein correlation profiling provides direct evidence that complex assembly buffers variation in gene copy number and transcription, a

SUBMITTER: Rosenberger G 

PROVIDER: S-EPMC13639060 | biostudies-literature | 2026 Jul

REPOSITORIES: biostudies-literature