The genomic response of skeletal muscle to methylprednisolone using microarrays: tailoring data mining to the structure of the pharmacogenomic time series.
High-throughput data collection using gene microarrays has great potential as a method for addressing the pharmacogenomics of complex biological systems. Similarly, mechanism-based pharmacokinetic/pharmacodynamic modeling provides a tool for formulating quantitative testable hypotheses concerning the responses of complex biological systems. As the response of such systems to drugs generally entails cascades of molecular events in time, a time series design provides the best approach to capturing the full scope of drug effects. A major problem in using microarrays for high-throughput data collection is sorting through the massive amount of data in order to identify probe sets and genes of interest. Due to its inherent redundancy, a rich time series containing many time points and multiple samples per time point allows for the use of less stringent criteria of expression, expression change and data quality for initial filtering of unwanted probe sets. The remaining probe sets can then become the focus of more intense scrutiny by other methods, including temporal clustering, functional clustering and pharmacokinetic/pharmacodynamic modeling, which provide additional ways of identifying the probes and genes of pharmacological interest.
Almon
Richard R
RR
Department of Biological Sciences, SUNY at Buffalo, Buffalo, NY 14260, USA. almon@eng.buffalo.edu
DuBois
Debra C
DC
Piel
William H
WH
Jusko
William J
WJ
D000315:Adrenalectomy; D000818:Animals; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D010597:Pharmacogenetics / Q000379:methods*; D018075:RNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D018075:RNA, Complementary; D008775:Methylprednisolone