Use of gene networks from full genome microarray libraries to identify functionally relevant drug-affected genes and gene regulation cascades

Christopher J. Savoie, Sachiyo Aburatani, Shouji Watanabe, Yoshihiro Eguchi, Shigeru Muta, Seiya Imoto, Satoru Miyano, Satoru Kuhara, Kosuke Tashiro

Research output: Contribution to journalArticlepeer-review

47 Citations (Scopus)

Abstract

We developed an extensive yeast gene expression library consisting of full-genome cDNA array data for over 500 yeast strains, each with a single-gene disruption. Using this data, combined with dose and time course expression experiments with the oral antifungal agent griseofulvin, whose exact molecular targets were previously unknown, we used Boolean and Bayesian network discovery techniques to determine the gene expression regulatory cascades affected directly by this drug. Using this method we identified CIK1 as an important affected target gene related to the functional phenotype induced by griseofulvin. Cellular functional analysis of griseofulvin showed similar tubulin-specific morphological effects on mitotic spindle formation to those of the drug, in agreement with the known function of CIK1p. Further, using the nonparametric, nonlinear Bayesian gene networks we were able to identify alternative ligand-dependant transcription factors and G protein homologues upstream of CIK1 that regulate CIK1 expression and might therefore serve as alternative molecular targets to induce the same molecular response as griseofulvin.

Original languageEnglish
Pages (from-to)19-25
Number of pages7
JournalDNA Research
Volume10
Issue number1
DOIs
Publication statusPublished - 2003

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics

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