Systematic interpretation of genetic interactions using protein networks.
|Title||Systematic interpretation of genetic interactions using protein networks.|
|Publication Type||Journal Article|
|Year of Publication||2005|
|Authors||Kelley R, Ideker T|
|Date Published||2005 May|
|Keywords||Algorithms, Computer Simulation, Gene Expression Regulation, Models, Genetic, Protein Interaction Mapping, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Signal Transduction|
Genetic interaction analysis,in which two mutations have a combined effect not exhibited by either mutation alone, is a powerful and widespread tool for establishing functional linkages between genes. In the yeast Saccharomyces cerevisiae, ongoing screens have generated >4,800 such genetic interaction data. We demonstrate that by combining these data with information on protein-protein, prote in-DNA or metabolic networks, it is possible to uncover physical mechanisms behind many of the observed genetic effects. Using a probabilistic model, we found that 1,922 genetic interactions are significantly associated with either between- or within-pathway explanations encoded in the physical networks, covering approximately 40% of known genetic interactions. These models predict new functions for 343 proteins and suggest that between-pathway explanations are better than within-pathway explanations at interpreting genetic interactions identified in systematic screens. This study provides a road map for how genetic and physical interactions can be integrated to reveal pathway organization and function.
|Alternate Title||Nat. Biotechnol.|