Abstract

To elucidate cellular machinery on a global scale, we performed a multiple comparison of the newly-available protein-protein interaction networks of C. elegans, D. melanogaster and S. cerevisiae. This comparison integrated protein interaction and sequence information to reveal 71 network regions that were conserved across all three species and many exclusive to the metazoans. Using this conservation we found statistically-significant support for 4,645 new protein functions and 2,609 new protein interactions. We tested sixty interaction predictions for yeast by two-hybrid assays, confirming approximately half of these. Significantly, many of the predicted functions and interactions would not have been identified from sequence similarity alone, demonstrating that network comparisons provide essential biological information beyond what is gleaned from the genome.