Bridging Structural Biology and Genomics: Assessing genome-wide protein-protein interaction datasets using the structures of known protein complexes

There is a large effort to map protein-protein interactions on a genome-wide scale. The utility of the resulting interaction networks depends on the reliability of the experimental methods and coverage of the approaches. Known macromolecular complexes provide a defined and objective set of protein interactions to which biochemical and genetic data can be compared and validated. We show a significant fraction of the protein-protein interactions in genome-wide datasets, as well as many of the individual interactions reported in the literature, were inconsistent with the known 3D structures of three recent complexes (RNA polII, Arp2/3 and the proteasome). Furthermore, comparison amongst genome-wide datasets and between them and a larger (but less well resolved) group of 174 complexes also shows marked inconsistencies. Finally, individual interaction datasets, being inherently noisy, are best used when integrated together, and we show how simple Bayesian approaches can combine them, significantly decreasing error rate.