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Toward a comprehensive atlas of the physical interactome of Saccharomyces cerevisiae
Author(s): Collins SR (Collins, Sean R.), Kemmeren P (Kemmeren, Patrick), Zhao XC (Zhao, Xue-Chu), Greenblatt JF (Greenblatt, Jack F.), Spencer F (Spencer, Forrest), Holstege FCP (Holstege, Frank C. P.), Weissman JS (Weissman, Jonathan S.), Krogan NJ (Krogan, Nevan J.)
Source: MOLECULAR & CELLULAR PROTEOMICS    Volume: 6    Issue: 3    Pages: 439-450    Published: MAR 2007  
Times Cited: 111     References: 49     
Abstract: Defining protein complexes is critical to virtually all aspects of cell biology. Two recent affinity purification/mass spectrometry studies in Saccharomyces cerevisiae have vastly increased the available protein interaction data. The practical utility of such high throughput interaction sets, however, is substantially decreased by the presence of false positives. Here we created a novel probabilistic metric that takes advantage of the high density of these data, including both the presence and absence of individual associations, to provide a measure of the relative confidence of each potential protein-protein interaction. This analysis largely overcomes the noise inherent in high throughput immunoprecipitation experiments. For example, of the 12,122 binary interactions in the general repository of interaction data (BioGRID) derived from these two studies, we marked 7504 as being of substantially lower confidence. Additionally, applying our metric and a stringent cutoff we identified a set of 9074 interactions (including 4456 that were not among the 12,122 interactions) with accuracy comparable to that of conventional small scale methodologies. Finally we organized proteins into coherent multisubunit complexes using hierarchical clustering. This work thus provides a highly accurate physical interaction map of yeast in a format that is readily accessible to the biological community.
Document Type: Article
Language: English
Reprint Address: Weissman, JS (reprint author), Univ Calif San Francisco, Dept Mol & Cellular Pharmacol, San Francisco, CA 94158 USA
Addresses:
1. Univ Calif San Francisco, Dept Mol & Cellular Pharmacol, San Francisco, CA 94158 USA
2. Univ Calif San Francisco, Calif Inst Quantitat Biomed Res, San Francisco, CA 94158 USA
3. Univ Utrecht, Med Ctr, Dept Physiol Chem, Div Biomed Genet, NL-3500 Utrecht, Netherlands
4. Johns Hopkins Univ, Sch Med, McKuisick Nathans Inst Genet Med, Baltimore, MD 21205 USA
5. Univ Toronto, Banting & Best Dept Med Res, Toronto, ON M5S 3E1 Canada
6. Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94158 USA
Publisher: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
Subject Category: Biochemical Research Methods
IDS Number: 150KE
ISSN: 1535-9476
DOI: 10.1074/mcp.M600381-MCP200
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