Building and analyzing protein interactome networks by cross-species comparisons

The connectivity of the resultant networks was determined to have scale-free distribution, small-world properties, and increased local modularity, indicating that the added interactions do not disrupt our current understanding of protein network structures. We show examples of how these improved interactomes can be used to analyze a genome-scale dataset (RNAi screen) and to assign new function to proteins. Predicted interactions within this dataset were tested by co-immunoprecipitation, resulting in a high rate of validation, suggesting the high quality of networks produced.Protein-protein interactions were predicted in five species, based on orthology. An InteroScore, a score accounting for homology, number of orthologues with evidence of interactions, and number of unique observations of interactions, is given to each known and predicted interaction. Our website http://www.interologfinder.org webcite provides research biologists intuitive access to this data.Proteins often physically interact to carry out their functions within living cells. A protein-protein interactome, or a protein-protein interaction (PPI) network, is the collection of these interactions between proteins in a single organism. The utility of generating a high quality PPI network with significant protein coverage for any species is manifold. It has been suggested that if two proteins interact, then they are likely to have related functions [1]. Therefore, perhaps the greatest benefit of a comprehensive PPI map will be to provide insight into the biology of proteins with no known function, a significant issue for all species in this "post-genomic era."Systematic identification of PPI has provided new insights into the relationships between both individual proteins and the processes within which they are involved. There have been several studies aimed at determining the full set of PPI for multiple model organisms [2-8], as well as for humans [9-11], and a wide range of publications on PPI at a mu