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Databases and tools for in silico analysis of regulation of gene expression

: Kel, A.; Kel-Margoulis, O.; Borlak, J.; Tchehekmenev, D.; Wingender, E.


Borlak, J.:
Handbook of toxicogenomics : Strategies and applications
Weinheim: Wiley-VCH, 2005
ISBN: 3-527-30342-1
Aufsatz in Buch
Fraunhofer ITEM ()
Genetic toxicology; Genetics; Proteomics; Gene expression

Regulation of gene expression is the key problem of the era of functional genomics. Now we know that genes in genomes of higher eukaryotic organisms are regulated mainly by means of multiple regulatory proteins - transcription factors (TF) - acting through specific regulatory sequences (TF binding sites) that are usually located
near the genes when they act as a promoter or at more remote locations when they are part of an enhancer. Having genomic sequences available on one hand and the massive, albeit phenomenological, amount of gene-expression data on the other hand, the challenge is to understand the regulatory mechanisms affecting every single gene in the genome by computer analysis of the gene regulatory sequences and by integrating these data with biological knowledge of gene signal transduction and metabolic and physiological networks. Sophisticated computational tools for regulatory sequence analysis that employ powerful statistical and machine-learning algorithms driven by the rich databases that collect biological facts enable us to make profound in-silico predictions and to formulate experimentally testable hypotheses. Such in-silico-driven experiments can greatly accelerate our understanding of gene regulatory mechanisms and the identification of new target genes. Understanding how gene regulation mechanisms are encoded in the genomic regulatory sequences will give us a powerful means for deciphering causes of major human diseases.