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| Systematic interpretation of genetic interactions using protein networks |
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| Author(s): Kelley R, Ideker T |
| Source: NATURE BIOTECHNOLOGY Volume: 23 Issue: 5 Pages: 561-566 Published: MAY 2005 |
| Times Cited: 100 References: 37 |
| Abstract: 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 ∼ 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. |
| Document Type: Article |
| Language: English |
| Reprint Address: Ideker, T (reprint author), Univ Calif San Diego, Program Bioinformat, 9500 Gilman Dr, La Jolla, CA 92093 USA |
Addresses:
1. Univ Calif San Diego, Program Bioinformat, La Jolla, CA 92093 USA
2. Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA |
| Publisher: NATURE PUBLISHING GROUP, 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA |
| Subject Category: Biotechnology & Applied Microbiology |
| IDS Number: 923XS |
| ISSN: 1087-0156 |
| DOI: 10.1038/nbt1096 |
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