A recent paper by Kelly and Ideker in Nature Biotechnology discusses how genetic and physical interactions can be integrated to reveal pathway organization and function. These 'systems biology' studies have great potential for the study of human health (see Moore, Nat Genet. 2005 Jan;37(1):13-4 [PubMed]; Moore and Williams, BioEssays. 2005 Jun;27(6):637-46 [PubMed]).
Kelley R, Ideker T. Systematic interpretation of genetic interactions using protein networks. Nat Biotechnol. 2005 May;23(5):561-6. [PubMed]
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.