Beyond microarrays: Finding key transcription factors controlling signal transduction pathways

Alexdander Kel, Nico Voss, Ruy Jauregui, Olga Kel-Margoulis, Edgar Wingender
2006 BMC Bioinformatics  
Massive gene expression changes in different cellular states measured by microarrays, in fact, reflect just an "echo" of real molecular processes in the cells. Transcription factors constitute a class of the regulatory molecules that typically require posttranscriptional modifications or ligand binding in order to exert their function. Therefore, such important functional changes of transcription factors are not directly visible in the microarray experiments. Results: We developed a novel
more » ... ch to find key transcription factors that may explain concerted expression changes of specific components of the signal transduction network. The approach aims at revealing evidence of positive feedback loops in the signal transduction circuits through activation of pathway-specific transcription factors. We demonstrate that promoters of genes encoding components of many known signal transduction pathways are enriched by binding sites of those transcription factors that are endpoints of the considered pathways. Application of the approach to the microarray gene expression data on TNF-alpha stimulated primary human endothelial cells helped to reveal novel key transcription factors potentially involved in the regulation of the signal transduction pathways of the cells. Conclusion: We developed a novel computational approach for revealing key transcription factors by knowledge-based analysis of gene expression data with the help of databases on gene regulatory networks (TRANSFAC ® and TRANSPATH ® ). The corresponding software and databases are available at http://www.gene-regulation.com. Background New high-throughput methods, such as microarrays, allow generation of massive amounts of molecular bio-logical data. These, mainly phenomenological, data are often difficult to relate with the activation/inhibition of particular signal transduction pathways and/or transcrip-
doi:10.1186/1471-2105-7-s2-s13 pmid:17118134 pmcid:PMC1683568 fatcat:zdusg6vf2jhqzcknrr3cletlwy