Systematic interpretation of genetic interactions using protein networks

被引:323
作者
Kelley, R
Ideker, T
机构
[1] Univ Calif San Diego, Program Bioinformat, La Jolla, CA 92093 USA
[2] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA
关键词
D O I
10.1038/nbt1096
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
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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收藏
页码:561 / 566
页数:6
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