| Predicting the phenotypic effects of mutations is a central goal of genetics research; it has important applications in understanding how genotype determines phenotype, and also in identifying human disease genes. Using a wide range of functional genomic data types 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. Similarly, we find that a proxy for protein complexes is a powerful predictor of disease phenotypes in human. 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 effective model for investigating, and even predicting, the genetic basis of both mendelian and complex disease phenotypes. |
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