Using protein complexes to predict phenotypic effects of gene mutation

Hunter B Fraser¹ and Joshua B Plotkin²

¹Broad Institute of Harvard and MIT, 320 Charles St, Cambridge, Massachhusetts 02142, USA

²Department of Biology, University of Pennsylvania, 433 S. University Ave, Philadelphia, Pennsylvania 19104, USA

author email corresponding author email

Genome Biology 2007, 8:R252doi:10.1186/gb-2007-8-11-r252


Published:	27 November 2007

Subject areas: Bioinformatics, Genetics, Medicine

Abstract

Background

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.

Results

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.

Conclusion

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.