Abstract
BackgroundSynthetic lethal genetic interactions among proteins have been widely used to define functional relationships between proteins and pathways. However, the molecular mechanism of synthetic lethal genetic interactions is still unclear.ResultsIn 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.ConclusionThe identification of domain genetic interactions helps the understanding of originality of functional relationship in SLGIs at domain level. Our study significantly improved the understanding of yeast mulitdomain proteins, the synthetic lethal genetic interactions and the functional relationships between proteins and pathways.
Highlights
Synthetic lethal genetic interactions among proteins have been widely used to define functional relationships between proteins and pathways
We identified significant domain genetic interactions, which rarely overlap with the domain physical interactions from iPfam database [20]
Identification of Significant Domain Genetic Interactions Using Maximum Likelihood Estimation By assuming the independences among domain genetic interactions, we estimated the probabilities of domain genetic interactions using the Maximum Likelihood estimation (MLE) method
Summary
Synthetic lethal genetic interactions among proteins have been widely used to define functional relationships between proteins and pathways. Defining the functional relationships between proteins is one of the important tasks in the post-genomic era. Genetic interaction refers to the phenomenon in which the combined effect of mutations of two genes differs from individual effects of each mutation [2]. Mutation of two nonessential genes could lead to a lethal phenotype. This kind of genetic interactions is referred as synthetic lethal genetic interactions (SLGIs). The genome-wide SLGIs have attracted much attention as they are capable of defining the genome-wide functional relationships between proteins, pathways and complexes [2,3,4].
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