TY - JOUR T1 - Defining hierarchical protein interaction networks from spectral analysis of bacterial proteomes JF - bioRxiv DO - 10.1101/2021.09.28.462107 SP - 2021.09.28.462107 AU - Mark A. Zaydman AU - Alexander Little AU - Fidel Haro AU - Valeryia Aksianiuk AU - William J. Buchser AU - Aaron DiAntonio AU - Jeffrey I. Gordon AU - Jeffrey Milbrandt AU - Arjun S. Raman Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/09/28/2021.09.28.462107.abstract N2 - Cellular phenotypes emerge from a hierarchy of molecular interactions: proteins interact to form complexes, pathways, and phenotypes. We show that hierarchical networks of protein interactions can be extracted from the statistical pattern of proteome variation as measured across thousands of bacteria and that these hierarchies reflect the emergence of complex bacterial phenotypes. We describe the mathematics underlying our statistical approach and validate our results through gene-set enrichment analysis and comparison to existing experimentally-derived hierarchical databases. We demonstrate the biological utility of our unbiased hierarchical models by creating a model of motility in Pseudomonas aeruginosa and using it to discover a previously unappreciated genetic effector of twitch-based motility. Overall, our approach, SCALES (Spectral Correlation Analysis of Layered Evolutionary Signals), predicts hierarchies of protein interaction networks describing emergent biological function using only the statistical pattern of bacterial proteome variation.Competing Interest StatementThe authors have declared no competing interest. ER -