Cross-species chemogenomic profiling reveals evolutionarily conserved drug mode of action

Mol Syst Biol. 2010 Dec 21;6:451. doi: 10.1038/msb.2010.107.

Abstract

We present a cross-species chemogenomic screening platform using libraries of haploid deletion mutants from two yeast species, Saccharomyces cerevisiae and Schizosaccharomyces pombe. We screened a set of compounds of known and unknown mode of action (MoA) and derived quantitative drug scores (or D-scores), identifying mutants that are either sensitive or resistant to particular compounds. We found that compound-functional module relationships are more conserved than individual compound-gene interactions between these two species. Furthermore, we observed that combining data from both species allows for more accurate prediction of MoA. Finally, using this platform, we identified a novel small molecule that acts as a DNA damaging agent and demonstrate that its MoA is conserved in human cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antifungal Agents / metabolism
  • Antifungal Agents / pharmacology*
  • DNA Damage
  • Drug Resistance, Fungal*
  • Gene Expression Profiling
  • Gene Expression Regulation, Fungal / drug effects*
  • Genes, Fungal
  • Genome, Fungal / drug effects
  • Humans
  • Microbial Sensitivity Tests*
  • Mutagenesis
  • Saccharomyces cerevisiae / drug effects*
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism
  • Schizosaccharomyces / drug effects*
  • Schizosaccharomyces / genetics*
  • Schizosaccharomyces / metabolism
  • Sequence Deletion

Substances

  • Antifungal Agents