Using protein complexes to predict phenotypic effects of gene mutation.
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.


CONCLUSIONS
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.
Fraser
Hunter B
HB
Broad Institute of Harvard and MIT, 320 Charles St, Cambridge, Massachhusetts 02142, USA. hunter@broad.mit.edu
Plotkin
Joshua B
JB
D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D009154:Mutation; D010641:Phenotype; D012441:Saccharomyces cerevisiae / Q000235:genetics