Jump to main content
Jump to site search

Issue 4, 2013
Previous Article Next Article

Predicting drug–target interactions through integrative analysis of chemogenetic assays in yeast

Author affiliations

Abstract

Chemical-genomic and genetic interaction profiling approaches are widely used to study mechanisms of drug action and resistance. However, there exist a number of scoring algorithms customized to different experimental assays, the relative performance of which remains poorly understood, especially with respect to different types of chemogenetic assays. Using yeast Saccharomyces cerevisiae as a test bed, we carried out a systematic evaluation among the main drug target analysis approaches in terms of predicting global drug–target interaction networks. We found drastic differences in their performance across different chemical-genomic assay types, such as those based on heterozygous and homozygous diploid or haploid deletion mutant libraries. Moreover, a relatively small overlap in the predicted targets was observed between those approaches that use either chemical-genomic screening alone or combined with genetic interaction profiling. A rank-based integration of the complementary scoring approaches led to improved overall performance, demonstrating that genetic interaction profiling provides added information on drug target prediction. Optimal performance was achieved when focusing specifically on the negative tail of the genetic interactions, suggesting that combining synthetic lethal interactions with chemical–genetic interactions provides highest information on drug–target interactions. A network view of rapamycin-interacting genes, pathways and complexes was used as an example to demonstrate the benefits of such integrated and optimized analysis of chemogenetic assays in yeast.

Graphical abstract: Predicting drug–target interactions through integrative analysis of chemogenetic assays in yeast

Back to tab navigation

Supplementary files

Publication details

The article was received on 20 Dec 2012, accepted on 31 Jan 2013 and first published on 31 Jan 2013


Article type: Paper
DOI: 10.1039/C3MB25591C
Citation: Mol. BioSyst., 2013,9, 768-779
  • Open access: Creative Commons BY license
  •   Request permissions

    Predicting drug–target interactions through integrative analysis of chemogenetic assays in yeast

    M. A. Heiskanen and T. Aittokallio, Mol. BioSyst., 2013, 9, 768
    DOI: 10.1039/C3MB25591C

    This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. Material from this article can be used in other publications provided that the correct acknowledgement is given with the reproduced material.

    Reproduced material should be attributed as follows:

    • For reproduction of material from NJC:
      [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the Centre National de la Recherche Scientifique (CNRS) and the RSC.
    • For reproduction of material from PCCP:
      [Original citation] - Published by the PCCP Owner Societies.
    • For reproduction of material from PPS:
      [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the European Society for Photobiology, the European Photochemistry Association, and RSC.
    • For reproduction of material from all other RSC journals:
      [Original citation] - Published by The Royal Society of Chemistry.

    Information about reproducing material from RSC articles with different licences is available on our Permission Requests page.

Search articles by author

Spotlight

Advertisements