Pharmacogenomic responses of rat liver to methylprednisolone: An approach to mining a rich microarray time series

Journal Title: The AAPS Journal - Year 2005, Vol 7, Issue 1

Abstract

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 preparation 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.

Authors and Affiliations

Richard R. Almon, Debra C. Dubois, Jin Y. Jin, William J. Jusko

Keywords

Related Articles

Recent Advances on the Role of G Protein-Coupled Receptors in Hypoxia-Mediated Signaling

G protein-coupled receptors (GPCRs) are cell surface proteins mainly involved in signal transmission; however, they play a role also in several pathophysiological conditions. Chemically heterogeneous molecules like pepti...

Guidelines for the Quality Control of Population Pharmacokinetic–Pharmacodynamic Analyses: an Industry Perspective

Quality population modeling and simulation analyses and reports are something every modeler desires. However, little attention in the literature has been paid to what constitutes quality regarding population analyses. Ve...

Antinociceptive Effects of Racemic AM1241 and Its Chirally Synthesized Enantiomers: Lack of Dependence upon Opioid Receptor Activation

The online version of this article (doi:10.1208/s12248-009-9170-8) contains supplementary material, which is available to authorized users.

Delivery of siRNA Therapeutics: Barriers and Carriers

RNA interference is a naturally occurring endogenous regulatory process where short double-stranded RNA causes sequence-specific posttranscriptional gene silencing. Small interference RNA (siRNA) represents a promising t...

Quality by Design: Concepts for ANDAs

Quality by design is an essential part of the modern approach to pharmaceutical quality. There is much confusion among pharmaceutical scientists in generic drug industry about the appropriate element and terminology of q...

Download PDF file
  • EP ID EP681861
  • DOI  10.1208/aapsj070117
  • Views 90
  • Downloads 0

How To Cite

Richard R. Almon, Debra C. Dubois, Jin Y. Jin, William J. Jusko (2005). Pharmacogenomic responses of rat liver to methylprednisolone: An approach to mining a rich microarray time series. The AAPS Journal, 7(1), -. https://europub.co.uk/articles/-A-681861