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
[31]   Identification of toxicologically predictive gene sets using cDNA microarrays [J].
Thomas, RS ;
Rank, DR ;
Penn, SG ;
Zastrow, GM ;
Hayes, KR ;
Pande, K ;
Glover, E ;
Silander, T ;
Craven, MW ;
Reddy, JK ;
Jovanovich, SB ;
Bradfield, CA .
MOLECULAR PHARMACOLOGY, 2001, 60 (06) :1189-1194
[32]   Significance analysis of microarrays applied to the ionizing radiation response [J].
Tusher, VG ;
Tibshirani, R ;
Chu, G .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (09) :5116-5121
[33]   Diverse roles of the nuclear orphan receptor CAR in regulating hepatic genes in response to phenobarbital [J].
Ueda, A ;
Hamadeh, HK ;
Webb, HK ;
Yamamoto, Y ;
Sueyoshi, T ;
Afshari, CA ;
Lehmann, JM ;
Negishi, M .
MOLECULAR PHARMACOLOGY, 2002, 61 (01) :1-6
[34]   Clustering of hepatotoxins based on mechanism of toxicity using gene expression profiles [J].
Waring, JF ;
Jolly, RA ;
Ciurlionis, R ;
Lum, PY ;
Praestgaard, JT ;
Morfitt, DC ;
Buratto, B ;
Roberts, C ;
Schadt, E ;
Ulrich, RG .
TOXICOLOGY AND APPLIED PHARMACOLOGY, 2001, 175 (01) :28-42
[35]   Specific and overlapping functions of the nuclear hormone receptors CAR and PXR in xenobiotic response [J].
Wei P. ;
Zhang J. ;
Dowhan D.H. ;
Han Y. ;
Moore D.D. .
The Pharmacogenomics Journal, 2002, 2 (2) :117-126
[36]   An information-intensive approach to the molecular pharmacology of cancer [J].
Weinstein, JN ;
Myers, TG ;
OConnor, PM ;
Friend, SH ;
Fornace, AJ ;
Kohn, KW ;
Fojo, T ;
Bates, SE ;
Rubinstein, LV ;
Anderson, NL ;
Buolamwini, JK ;
vanOsdol, WW ;
Monks, AP ;
Scudiero, DA ;
Sausville, EA ;
Zaharevitz, DW ;
Bunow, B ;
Viswanadhan, VN ;
Johnson, GS ;
Wittes, RE ;
Paull, KD .
SCIENCE, 1997, 275 (5298) :343-349
[37]   BRCA1 transcriptionally regulates genes involved in breast tumorigenesis [J].
Welcsh, PL ;
Lee, MK ;
Gonzalez-Hernandez, RM ;
Black, DJ ;
Mahadevappa, M ;
Swisher, EM ;
Warrington, JA ;
King, MC .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (11) :7560-7565
[38]  
WHITLOCK JP, 1995, INDUCTION CYTOCHROME
[39]  
Xu H, 2001, Biotechnol Annu Rev, V7, P131, DOI 10.1016/S1387-2656(01)07035-1
[40]   Design issues for cDNA microarray experiments [J].
Yang, YH ;
Speed, T .
NATURE REVIEWS GENETICS, 2002, 3 (08) :579-588