  Genetic interactions have been widely used to define functional relationships
between proteins and pathways. In this study, we demonstrated that yeast
synthetic lethal genetic interactions can be explained by the genetic
interactions between domains of those proteins. The domain genetic interactions
rarely overlap with the domain physical interactions from iPfam database and
provide a complementary view about domain relationships. Moreover, we found
that domains in multidomain yeast proteins contribute to their genetic
interactions differently. The domain genetic interactions help more precisely
define the function related to the synthetic lethal genetic interactions, and
then help understand how domains contribute to different functionalities of
multidomain 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 the
predicted synthetic lethal genetic interactions. Our study significantly
improved the understanding of yeast mulitdomain proteins, the synthetic lethal
genetic interactions and the functional relationships between proteins and
pathways.
