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

被引:33
作者
Almon, RR
Dubois, DC
Jin, JY
Jusko, WJ
机构
[1] SUNY Buffalo, Dept Biol Sci, Buffalo, NY 14260 USA
[2] SUNY Buffalo, Dept Pharmaceut Sci, Buffalo, NY 14260 USA
关键词
data mining; gene arrays; glucocorticoids; mathematical modeling; pharmacogenomics;
D O I
10.1208/aapsj070117
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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. Copyright ©2003. All Rights Reserved.
引用
收藏
页码:E156 / E194
页数:39
相关论文
共 19 条
[1]   In vivo multi-tissue corticosteroid microarray time series available online at Public Expression Profile Resource (PEPR) [J].
Almon, RR ;
Chen, J ;
Snyder, G ;
DuBois, DC ;
Jusko, WJ ;
Hoffman, EP .
PHARMACOGENOMICS, 2003, 4 (06) :791-799
[2]   Pharmacodynamics and pharmacogenomics of diverse receptor-mediated effects of methylprednisolone in rats using microarray analysis [J].
Almon, RR ;
DuBois, DC ;
Brandenburg, EH ;
Shi, W ;
Zhang, SZ ;
Straubinger, RM ;
Jusko, WJ .
JOURNAL OF PHARMACOKINETICS AND PHARMACODYNAMICS, 2002, 29 (02) :103-129
[3]  
Bialas Michael C., 1998, Adverse Drug Reactions and Toxicological Reviews, V17, P227
[4]   Cluster analysis and display of genome-wide expression patterns [J].
Eisen, MB ;
Spellman, PT ;
Brown, PO ;
Botstein, D .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (25) :14863-14868
[5]   EFFECTS OF ADRENAL CORTICAL HORMONES ON CARBOHYDRATE, PROTEIN, AND FAT METABOLISM [J].
EISENSTEIN, A .
AMERICAN JOURNAL OF CLINICAL NUTRITION, 1973, 26 (01) :113-120
[6]  
Frauman AG, 1996, ADVERSE DRUG REACT T, V15, P203
[7]  
Friedman N, 2002, E SCHERING RES FDN W, V38, P109
[8]   Modeling of corticosteroid pharmacogenomics in rat liver using gene microarrays [J].
Jin, JY ;
Almon, RR ;
Dubois, DC ;
Jusko, WJ .
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2003, 307 (01) :93-109
[9]  
Kaminski N, 2003, AM J RESP CELL MOL, V29, pS32
[10]   Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis [J].
Lock, C ;
Hermans, G ;
Pedotti, R ;
Brendolan, A ;
Schadt, E ;
Garren, H ;
Langer-Gould, A ;
Strober, S ;
Cannella, B ;
Allard, J ;
Klonowski, P ;
Austin, A ;
Lad, N ;
Kaminski, N ;
Galli, SJ ;
Oksenberg, JR ;
Raine, CS ;
Heller, R ;
Steinman, L .
NATURE MEDICINE, 2002, 8 (05) :500-508