All-by-all discovery of conserved protein complexes by deep proteome fractionation
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Stable assemblies of proteins, known as protein complexes, execute a large fraction of cellular processes required to sustain life. A functional and mechanistic understanding of these assemblies will provide a more comprehensive understanding of an organisms genes and elucidate a more complete picture of cellular processes, particularly those involved in development, aging and disease. While recent progress has mapped protein complexes in budding yeast and some bacteria, efforts in animals are restricted to subsets of the proteome, leaving most animal protein complexes undetermined. Co-fractionation offers compelling efficiency gains in identifying pairwise protein interactions and complexes, but it requires significant computational efforts to fully exploit. In this work, I describe the computational methods and infrastructure I developed to identify conserved protein interactions and complexes from a massive set of mass spectrometry data from nine species and the computational and biological analysis I performed with my collaborators. These efforts include building a mostly automated pipeline to process and integrate large quantities of mass spectrometry data from multiple species and developing improved methods to predict co-complex interactions and cluster them into complexes. The conserved animal complex map produced using this pipeline and methodology has already yielded dividends in supporting biological discoveries. Scaling the approach more broadly will enable rapid mapping of the previously uncharted interactomes in any chosen species.