期刊
NATURE BIOTECHNOLOGY
卷 23, 期 5, 页码 561-566出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nbt1096
关键词
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资金
- NIGMS NIH HHS [GM070743-01, R01 GM070743-02, R01 GM070743-01, R01 GM070743] Funding Source: Medline
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 similar to 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.
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