BioPlex: a Protein Interaction Network Created from Thousands of Protein Immunopurifications
Featured Expert: Steven Gygi, PhD, Harvard Medical School
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Protein-protein interactions form a network whose structure drives cellular function and whose organization informs all biological inquiry. Using high-throughput affinity-purification mass spectrometry, we identify interacting partners for 2,594 human proteins in HEK293T cells. The resulting network (BioPlex) contains 23,744 interactions, 86% unknown, among 7,668 proteins. BioPlex accurately depicts known complexes, attaining 80-100% coverage for most CORUM complexes. Network structure reveals 4 key features: 1) BioPlex subdivides into over 300 communities, uniting proteins with shared function. 2) Interactions predict 2,968 associations among co-occurring Pfam domains. 3) Attributes including localization, biological process, and molecular function were determined for thousands of proteins - many uncharacterized. 4) BioPlex reveals interactions of biological or clinical significance. To demonstrate complementary studies inspired by BioPlex, we interrogated interactions of wild-type and mutant VAPB variants implicated in familial Amyotrophic Lateral Sclerosis. The network provides a framework for hypothesis generation and refinement as applied to protein function, mechanism, and activity. This webinar demonstrates how affinity purifications can be performed at scale, with associated caveats, and how an interaction network can be used to predict a protein’s cellular properties.
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