Pharmacogenomic responses of rat liver to methylprednisolone: an approach to mining a rich microarray time series.
A data set was generated to examine global changes in gene expression in rat liver over time in response to a single bolus dose of methylprednisolone. Four control animals and 43 drug-treated animals were humanely killed at 16 different time points following drug administration. Total RNA preparations from the livers of these animals were hybridized to 47 individual Affymetrix RU34A gene chips, generating data for 8799 different probe sets for each chip. Data mining techniques that are applicable to gene array time series data sets in order to identify drug-regulated changes in gene expression were applied to this data set. A series of 4 sequentially applied filters were developed that were designed to eliminate probe sets that were not expressed in the tissue, were not regulated by the drug treatment, or did not meet defined quality control standards. These filters eliminated 7287 probe sets of the 8799 total (82%) from further consideration. Application of judiciously chosen filters is an effective tool for data mining of time series data sets. The remaining data can then be further analyzed by clustering and mathematical modeling techniques.
Almon
Richard R
RR
Department of Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, NY 14260, USA. almon@eng.buffalo.edu
Dubois
Debra C
DC
Jin
Jin Y
JY
Jusko
William J
WJ
D000315:Adrenalectomy; D000465:Algorithms; D000818:Animals; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D015345:Oligonucleotide Probes / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000096:biosynthesis / Q000235:genetics*; D015203:Reproducibility of Results; D013382:Subtraction Technique; D013997:Time Factors
D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D008775:Methylprednisolone