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Genome Biol. 2007;8(11):R252.

Using protein complexes to predict phenotypic effects of gene mutation.

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  • 1Broad Institute of Harvard and MIT, 320 Charles St, Cambridge, Massachhusetts 02142, USA. hunter@broad.mit.edu



Predicting the phenotypic effects of mutations is a central goal of genetics research; it has important applications in elucidating how genotype determines phenotype and in identifying human disease genes.


Using a wide range of functional genomic data from the yeast Saccharomyces cerevisiae, we show that the best predictor of a protein's knockout phenotype is the knockout phenotype of other proteins that are present in a protein complex with it. Even the addition of multiple datasets does not improve upon the predictions made from protein complex membership. Similarly, we find that a proxy for protein complexes is a powerful predictor of disease phenotypes in humans.


We propose that identifying human protein complexes containing known disease genes will be an efficient method for large-scale disease gene discovery, and that yeast may prove to be an informative model system for investigating, and even predicting, the genetic basis of both Mendelian and complex disease phenotypes.

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