Department of Biomedical Engineering, The Johns Hopkins University, Baltimore, MD, USA-
Abstract: We predicted gene function using synthetic lethal genetic interactions between null alleles in Saccharomyces cerevisiae- Phenotypic and protein interaction data indicate that synthetic lethal gene pairs function in parallel or compensating pathways- Congruent gene pairs, defined as sharing synthetic lethal partners, are in single pathway branches- We predicted benomyl sensitivity and nuclear migration defects using congruence; these phenotypes were uncorrelated with direct synthetic lethality- We also predicted YLL049W as a new member of the dynein-dynactin pathway and provided new supporting experimental evidence- We performed synthetic lethal screens of the parallel mitotic exit network -MEN- and Cdc14 early anaphase release pathways required for late cell cycle- Synthetic lethal interactions bridged genes in these pathways, and high congruence linked genes within each pathway- Synthetic lethal interactions between MEN and all components of the Sin3-Rpd3 histone deacetylase revealed a novel function for Sin3-Rpd3 in promoting mitotic exit in parallel to MEN- These in silico methods can predict phenotypes and gene functions and are applicable to genomic synthetic lethality screens in yeast and analogous RNA interference screens in metazoans-