Using protein complexes to predict phenotypic effects of gene mutation
1 Broad Institute of Harvard and MIT, 320 Charles St, Cambridge, Massachhusetts 02142, USA
2 Department of Biology, University of Pennsylvania, 433 S. University Ave, Philadelphia, Pennsylvania 19104, USA
Genome Biology 2007, 8:R252 doi:10.1186/gb-2007-8-11-r252Published: 27 November 2007
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.