A network analysis of synthetic lethal genetic interaction.
Sharyl L. Wong (1), Lan V. Zhang (1), Gabriel F. Berriz (1), Debra S. Goldberg (1), Oliver D. King (1), Amy H. Y. Tong (2), Zhijian Li (2), Guillaume Lesage (3), Brenda Andrews (2), Howard Bussey (3), Marc Vidal (4), Charles Boone (2), Frederick P. Roth (1)
(1) Biol Chem & Molec Pharm. Dept., Harvard Medical School, 250 Longwood Ave, Boston, MA, 02115, USA;
(2) Banting and Best Dept. of Medical Research and Dept. of Medical Genetics and Microbiology, University of Toronto, Canada.;
(3) Dept. of Biology, McGill University, Montreal PQ, Canada.;
(4) Dept. of Cancer Biology, Dana-Farber Cancer Institute and Dept. of Genetics, Harvard Medical School, Boston, MA, USA.
Two genes have a synthetic lethal interaction with one another if a combination of their mutant alleles, neither lethal alone, causes cell death. Such an interaction represents genetic buffering of one gene by another and contributes to the robustness of an organism to mutation. We examined synthetic sick or lethal (SSL) genetic interactions from a recent systematic genetic analysis (SGA) of ~500,000 gene pairs in S. cerevisiae. Results from SSL network analysis include: 1) a description of genetic network topology; 2) the demonstrated value of SSL interactions in characterizing gene function; 3) quantified relationships between the genetic network and other biological networks, including protein, expression, and sequence homology; 4) the exploitation of these relationships to predict synthetic genetic interactions, with relevance to drug target discovery, developing therapies using combinations of drugs, and mapping multigenic human diseases.
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