COSNeti: ComplexOme-Structural Network Interpreter used to study spatial enrichment in metazoan ribosomes

Abstract

Background: Upon environmental stimuli, ribosomes are surmised to undergo com‑ positional rearrangements due to abundance changes among proteins assembled into the complex, leading to modulated structural and functional characteristics. Here, we present the ComplexOme-Structural Network Interpreter (COSNeti), a computational method to allow testing whether ribosomal proteins (rProteins) that exhibit abundance changes under specifc conditions are spatially confned to particular regions within the large ribosomal complex.<p> <p>Results: COSNeti translates experimentally determined structures into graphs, with nodes representing proteins and edges the spatial proximity between them. In its frst implementation, COSNeti considers rProteins and ignores rRNA and other objects. Spatial regions are defned using a random walk with restart methodology, followed by a procedure to obtain a minimum set of regions that cover all proteins in the complex. Structural coherence is achieved by applying weights to the edges refecting the physi‑ cal proximity between purportedly contacting proteins. The weighting probabilistically guides the random-walk path trajectory. Parameter tuning during region selection provides the option to tailor the method to specifc biological questions by yielding regions of diferent sizes with minimum overlaps. In addition, other graph community detection algorithms may be used for the COSNeti workfow, considering that they yield diferent sized, non-overlapping regions. All tested algorithms result in the same node kernels under equivalent regions. Based on the defned regions, available abun‑ dance change information of proteins is mapped onto the graph and subsequently tested for enrichment in any of the defned spatial regions. We applied COSNeti to the cytosolic ribosome structures of Saccharomyces cerevisiae, Oryctolagus cuniculus, and Triticum aestivum using datasets with available quantitative protein abundance change information. We found that in yeast, substoichiometric rProteins depleted from translat‑ ing polysomes are signifcantly constrained to a ribosomal region close to the tRNA entry and exit sites.<p><p> Conclusions: COSNeti ofers a computational method to partition multi-protein com‑ plexes into structural regions and a statistical approach to test for spatial enrichments of any given subsets of proteins. COSNeti is applicable to any multi-protein complex given appropriate structural and abundance-change data. COSNeti is publicly available as a GitHub repository https://github.com/MSeidelFed/COSNet_i and can be installed using the python installer pip.