Global insights into protein complexes through integrated analysis of the reliable interactome and knockout lethality

We performed an integrated computational analysis of data derived from a comprehensive set of protein-protein interactions (interactome) and a phenotype dataset on lethality in Saccharomyces cerevisiae. For the analysis, we selected reliable interactome data using our previous 'interaction generality,' a computational approach to assess reliability of interactions. Those efforts gave clear evidence that proteins with lethal phenotypes in knockout studies (lethal proteins) may interact with each other to form functional protein complexes to perform their cellular roles. However, our analysis indicates that interactions between lethal proteins are rather restricted to the same cellular pathway or function, and it is quite unlikely that they interact with other lethal proteins functioning in different cellular roles. Furthermore, our results allowed us predictions on the functions of thus far uncharacterized lethal proteins with an estimated 93% accuracy. Thus, the analysis described in here can provide global insights into the biological features of the protein complexes.