Using expression and genotype to predict drug response in yeast

PLoS One. 2009 Sep 4;4(9):e6907. doi: 10.1371/journal.pone.0006907.

Abstract

Personalized, or genomic, medicine entails tailoring pharmacological therapies according to individual genetic variation at genomic loci encoding proteins in drug-response pathways. It has been previously shown that steady-state mRNA expression can be used to predict the drug response (i.e., sensitivity or resistance) of non-genotyped mammalian cancer cell lines to chemotherapeutic agents. In a real-world setting, clinicians would have access to both steady-state expression levels of patient tissue(s) and a patient's genotypic profile, and yet the predictive power of transcripts versus markers is not well understood. We have previously shown that a collection of genotyped and expression-profiled yeast strains can provide a model for personalized medicine. Here we compare the predictive power of 6,229 steady-state mRNA transcript levels and 2,894 genotyped markers using a pattern recognition algorithm. We were able to predict with over 70% accuracy the drug sensitivity of 104 individual genotyped yeast strains derived from a cross between a laboratory strain and a wild isolate. We observe that, independently of drug mechanism of action, both transcripts and markers can accurately predict drug response. Marker-based prediction is usually more accurate than transcript-based prediction, likely reflecting the genetic determination of gene expression in this cross.

Publication types

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

MeSH terms

  • Algorithms
  • Chemistry, Pharmaceutical / methods
  • Computational Biology / methods
  • Drug Evaluation, Preclinical / methods
  • Gene Expression Profiling
  • Gene Expression Regulation, Fungal*
  • Genetic Linkage
  • Genetic Markers
  • Genomics
  • Genotype
  • RNA, Messenger / metabolism
  • Reproducibility of Results

Substances

  • Genetic Markers
  • RNA, Messenger