Computational verification of protein-protein interactions by orthologous co-expression.

High-throughput methods identify an overwhelming number of protein-protein interactions. However, the limited accuracy of these methods results in the false identification of many spurious interactions. Accordingly, the resulting interactions are regarded as hypothetical and computational methods are needed to increase their confidence. Several methods have recently been suggested for this purpose including co-expression as a confidence measure for interacting proteins, but their performance is still quite poor. We introduce a novel computational method for verification of protein-protein interactions based on the co-expression of orthologs of interacting partners. The performance of our method is analysed using known S. cerevisiae interactions, and is shown to overcome limitations of previous methods. We present specific examples of known and putative interactions that are detected by our method and not by previous methods, and suggest that they represent transient interactions that might have been conserved and stabilized in other species. Co-expression of orthologous protein-pairs can be used to increase the confidence of hypothetical protein-protein interactions in S. cerevisiae as well as in other species. This approach may be especially useful for species with no available expression profiles and for transient interactions.