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Genetic interactions have been widely used to define functional relationshipsbetween proteins and pathways. In this study, we demonstrated that yeastsynthetic lethal genetic interactions can be explained by the geneticinteractions between domains of those proteins. The domain genetic interactionsrarely overlap with the domain physical interactions from iPfam database andprovide a complementary view about domain relationships. Moreover, we foundthat domains in multidomain yeast proteins contribute to their geneticinteractions differently. The domain genetic interactions help more preciselydefine the function related to the synthetic lethal genetic interactions, andthen help understand how domains contribute to different functionalities ofmultidomain proteins. Using the probabilities of domain genetic interactions,we were able to predict novel yeast synthetic lethal genetic interactions.Furthermore, we had also identified novel compensatory pathways from thepredicted synthetic lethal genetic interactions. Our study significantlyimproved the understanding of yeast mulitdomain proteins, the synthetic lethalgenetic interactions and the functional relationships between proteins andpathways.

Understanding and predicting synthetic lethal genetic interactions in Saccharomyces cerevisiae using domain genetic interactions