On the number of protein-protein interactions in the yeast proteome

Using two different approaches, we estimated that on average there are about five interacting partners per protein in the proteome of the yeast Saccharomyces cerevisiae. In the first approach, we used a novel method to model sampling overlap by a Bernoulli process, compared the results of two independent yeast two-hybrid interaction screens and tested the robustness of the estimate. The most stable estimate of five interactors per protein was obtained when the three most highly connected nodes in the protein interaction network were removed from the analysis (eight interactors per protein if those nodes were kept). In the second approach, we analysed a published high-confidence subset of putative interaction data obtained from multiple sources, including large-scale two-hybrid screens, complex purifications, synthetic lethals, correlated gene expression, computational predictions and previous annotations. Strikingly, the estimate was again five interactors per protein. These estimates suggest a range of ~16 000–26 000 different interaction pairs in the yeast, excluding homotypic interactions. We also discuss the approaches to estimating the rate of homotypic interactions.