Expression-based monitoring of transcription factor activity: the TELiS database

被引:143
作者
Cole, SW [1 ]
Yan, W
Galic, Z
Arevalo, J
Zack, JA
机构
[1] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA
[2] Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA
[3] Univ Calif Los Angeles, Dept Microbiol Mol Genet & Immunol, Los Angeles, CA 90095 USA
[4] Univ Calif Los Angeles, AIDS Inst, Los Angeles, CA 90095 USA
[5] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA
[6] Univ Calif Los Angeles, Inst Mol Biol, David Geffen Sch Med, Los Angeles, CA 90095 USA
关键词
D O I
10.1093/bioinformatics/bti038
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Motivation: In microarray studies it is often of interest to identify upstream transcription control pathways mediating observed changes in gene expression. The Transcription Element Listening System (TELiS) combines sequence-based analysis of gene regulatory regions with statistical prevalence analyses to identify transcription-factor binding motifs (TFBMs) that are over-represented among the promoters of up- or down-regulated genes. Efficiency is maximized by decomposing the problem into two steps: (1) a priori compilation of prevalence matrices specifying the number of putative binding sites for a variety of transcription factors in promoters from all genes assayed by a given microarray, and (2) real-time statistical analysis of pre-compiled prevalence matrices to identify TFBMs that are over- or under-represented in promoters of differentially expressed genes. The interlocking JAVA applications namely, PromoterScan and PromoterStats carry out these tasks, and together constitute the TELiS database for reverse inference of transcription factor activity. Results: In two validation studies, TELiS accurately detected in vivo activation of NF-kappa B and the Type I interferon system by HIV-1 infection and pharmacologic activation of the glucocorticoid receptor in peripheral blood mononuclear cells. The population-based statistical inference underlying TELiS out-performed conventional statistical tests in analytic sensitivity, with parametric studies demonstrating accurate identification of transcription factor activity from as few as 20 differentially expressed genes. TELiS thus provides a simple, rapid and sensitive tool for identifying transcription control pathways mediating observed gene expression dynamics.
引用
收藏
页码:803 / 810
页数:8
相关论文
共 43 条
[1]   THE SCID-HU MOUSE AS A MODEL FOR HIV-1 INFECTION [J].
ALDROVANDI, GM ;
FEUER, G ;
GAO, LY ;
JAMIESON, B ;
KRISTEVA, M ;
CHEN, ISY ;
ZACK, JA .
NATURE, 1993, 363 (6431) :732-736
[2]  
[Anonymous], 1989, STAT ANAL DISCRETE D
[3]   CONTROLLING THE FALSE DISCOVERY RATE - A PRACTICAL AND POWERFUL APPROACH TO MULTIPLE TESTING [J].
BENJAMINI, Y ;
HOCHBERG, Y .
JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES B-STATISTICAL METHODOLOGY, 1995, 57 (01) :289-300
[4]   Building a dictionary for genomes: Identification of presumptive regulatory sites by statistical analysis [J].
Bussemaker, HJ ;
Li, H ;
Siggia, ED .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (18) :10096-10100
[5]   Regulatory element detection using correlation with expression [J].
Bussemaker, HJ ;
Li, H ;
Siggia, ED .
NATURE GENETICS, 2001, 27 (02) :167-171
[6]  
CAREY M, 2000, TRANSCRIPTIONAL REGU
[7]  
Chiang D Y, 2001, Bioinformatics, V17 Suppl 1, pS49
[8]   Controlling false-negative errors in microarray differential expression analysis: a PRIM approach [J].
Cole, SW ;
Galic, Z ;
Zack, JA .
BIOINFORMATICS, 2003, 19 (14) :1808-1816
[9]   Temporal gene regulation during HIV-1 infection of human CD4+ T cells [J].
Corbeil, A ;
Sheeter, D ;
Genini, D ;
Rought, S ;
Leoni, L ;
Du, PY ;
Ferguson, M ;
Masys, DR ;
Welsh, JB ;
Fink, JL ;
Sasik, R ;
Huang, D ;
Drenkow, J ;
Richman, DD ;
Gingeras, T .
GENOME RESEARCH, 2001, 11 (07) :1198-1204
[10]   NF-κB and rel proteins:: Evolutionarily conserved mediators of immune responses [J].
Ghosh, S ;
May, MJ ;
Kopp, EB .
ANNUAL REVIEW OF IMMUNOLOGY, 1998, 16 :225-260