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1 Department of Biological Sciences, State University of New York at Buffalo, Buffalo, NY, USA; Department of Pharmaceutical Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, NY, USA
2 Department of Pharmaceutical Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, NY, USA
* To whom correspondence should be addressed. E-mail: almon{at}eng.buffalo.edu.
Kidney is a major target for adverse effects associated with corticosteroids. A microarray dataset was generated to examine changes in gene expression in rat kidney in response to methylprednisolone. Four control and 48 drug-treated animals were sacrificed at 16 times following drug administration. Kidney RNA was used to query 52 individual Affymetrix chips, generating data for 15967 different probe sets for each chip. Mining techniques applicable to time series data that identify drug-regulated changes in gene expression were applied. Four sequential filters eliminated probe sets that were not expressed in the tissue, not regulated by drug, or did not meet defined quality control standards. These filters eliminated 14890 probe sets (94%) from further consideration. Application of judiciously chosen filters is an effective tool for data mining of time series datasets. The remaining data can then be further analyzed by clustering and mathematical modeling. Initial analysis of this filtered dataset identified a group of genes whose pattern of regulation was highly correlated with prototype corticosteroid enhanced genes. Twenty genes in this group, as well as selected genes exhibiting either down-regulation or no regulation, were analyzed for 5' GRE half-sites conserved across species. In general the results support the hypothesis that the existence of conserved DNA binding sites can serve as an important adjunct to purely analytical approaches to clustering genes into groups with common mechanisms of regulation. This dataset, as well as similar datasets on liver and muscle, are available online in a format amenable to further analysis by others.
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