Systematic identification and correction of annotation errors in the genetic interaction map of Saccharomyces cerevisiae

Nucleic Acids Res. 2016 Mar 18;44(5):e50. doi: 10.1093/nar/gkv1284. Epub 2015 Nov 23.

Abstract

The yeast mutant collections are a fundamental tool in deciphering genomic organization and function. Over the last decade, they have been used for the systematic exploration of ∼6 000 000 double gene mutants, identifying and cataloging genetic interactions among them. Here we studied the extent to which these data are prone to neighboring gene effects (NGEs), a phenomenon by which the deletion of a gene affects the expression of adjacent genes along the genome. Analyzing ∼90,000 negative genetic interactions observed to date, we found that more than 10% of them are incorrectly annotated due to NGEs. We developed a novel algorithm, GINGER, to identify and correct erroneous interaction annotations. We validated the algorithm using a comparative analysis of interactions from Schizosaccharomyces pombe. We further showed that our predictions are significantly more concordant with diverse biological data compared to their mis-annotated counterparts. Our work uncovered about 9500 new genetic interactions in yeast.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms*
  • Epistasis, Genetic*
  • Gene Ontology
  • Genes, Fungal*
  • Genomics
  • Molecular Sequence Annotation / methods*
  • Protein Interaction Mapping
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism
  • Schizosaccharomyces / genetics
  • Schizosaccharomyces / metabolism