Better therapeutics through microarrays

被引:85
作者
Gerhold, DL
Jensen, RV
Gullans, SR
机构
[1] Harvard Univ, Sch Med, Brigham & Womens Hosp, Lab Funct Genom, Cambridge, MA 02139 USA
[2] Merck Res Labs, Dept Mol Profiling, W Point, PA 19486 USA
[3] Wesleyan Univ, Dept Phys, Middletown, CT 06459 USA
关键词
D O I
10.1038/ng1042
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
DNA microarrays are an integral part of the process for therapeutic discovery, optimization and clinical validation. At an early stage, investigators use arrays to prioritize a few genes as potential therapeutic targets on the basis of various criteria. Subsequently, gene expression analysis assists in drug discovery and toxicology by eliminating poor compounds and optimizing the selection of promising leads. Integral to this process is the use of sophisticated statistics, mathematics and bioinformatics to define statistically valid observations and to deduce complex patterns of phenotypes and biological pathways. In short, microarrays are redefining the drug discovery process by providing greater knowledge at each step and by illuminating the complex workings of biological systems.
引用
收藏
页码:547 / 552
页数:6
相关论文
共 40 条
[1]   Temporal gene expression analysis of monolayer cultured rat hepatocytes [J].
Baker, TK ;
Carfagna, MA ;
Gao, H ;
Dow, ER ;
Li, QQ ;
Searfoss, GH ;
Ryan, TP .
CHEMICAL RESEARCH IN TOXICOLOGY, 2001, 14 (09) :1218-1231
[2]   Toxicogenomics-based discrimination of toxic mechanism in HepG2 human hepatoma cells [J].
Burczynski, ME ;
McMillian, M ;
Ciervo, J ;
Li, L ;
Parker, JB ;
Dunn, RT ;
Hicken, S ;
Farr, S ;
Johnson, MD .
TOXICOLOGICAL SCIENCES, 2000, 58 (02) :399-415
[3]   Discovering functional relationships between RNA expression and chemotherapeutic susceptibility using relevance networks [J].
Butte, AJ ;
Tamayo, P ;
Slonim, D ;
Golub, TR ;
Kohane, IS .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (22) :12182-12186
[4]   Antisense DNAs as multisite genomic modulators identified by DNA microarray [J].
Cho, YS ;
Kim, MK ;
Cheadle, C ;
Neary, C ;
Becker, KG ;
Cho-Chung, YS .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (17) :9819-9823
[5]   Empirical Bayes methods and false discovery rates for microarrays [J].
Efron, B ;
Tibshirani, R .
GENETIC EPIDEMIOLOGY, 2002, 23 (01) :70-86
[6]   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
[7]   Diverse signaling pathways activated by growth factor receptors induce broadly overlapping, rather than independent, sets of genes [J].
Fambrough, D ;
McClure, K ;
Kazlauskas, A ;
Lander, ES .
CELL, 1999, 97 (06) :727-741
[8]  
Fryer RM, 2002, EXP NEPHROL, V10, P64
[9]   It's the genes! EST access to human genome content [J].
Gerhold, D ;
Caskey, CT .
BIOESSAYS, 1996, 18 (12) :973-981
[10]   Monitoring expression of genes involved in drug metabolism and toxicology using DNA microarrays [J].
Gerhold, D ;
Lu, MQ ;
Xu, J ;
Austin, C ;
Caskey, CT ;
Rushmore, T .
PHYSIOLOGICAL GENOMICS, 2001, 5 (04) :161-170