The integrated TRANSFAC system as a basis for modeling the architecture of gene regulatory networks

Anatolij Potapov1, Klaus Seidel1, Maik Christensen1, Volker Drewes1, Frank Schacherer1,2 and Edgar Wingender1,2




1GBF, German Research Centre for Biotechnology,
Mascheroder Weg 1,
D-38124 Braunschweig, Germany
2BIOBASE GmbH,
Halchtersche Strasse 33,
D-38304 Wolfenbüttel, Germany
Email: apo@gbf.de





More than a decade ago we began to compile information on transcriptional control of genes from the relevant original literature and organized it into a database. This database (TRANSFAC) contains information about regulating genome elements (sequences, localizations) as well as about the transcription factors that recognize those elements and act upon them in activating or repressing manner [1]. The database also comprises information about DNA-binding properties, expression patterns, and cellular mechanisms regulating the transcription factors.

Recently, a number of additional database modules extending our central database have been developed [1]. One of them (TRANSPATH) is a database that represents information about signal transduction pathways and cellular mechanisms regulating the activity of transcription factors [1, 2]. These data are intended for the simulation of signaling network dynamics. Under development is another database module (PathoPath) that aims at collecting data about mutated components of signal transduction pathways. Such components lead to pathological defects due to an impairment of gene regulation.

Finally, a comprehensive data resource on different aspects of gene regulation has been established. It provides an appropriate platform for modeling the architecture of regulatory pathways and networks that represents causal connections between network elements and is a logical skeleton of regulatory systems. By using a variant of the Boolean formalism, this enables an estimation of the influence of each network component on the regulatory output. Full integration of TRANSFAC and TRANSPATH allows to model complete signaling pathways starting with extracellular messengers (hormones, growth factors, cytokines, etc.), going through all the steps involving receptors, linking proteins, protein kinases, targeting transcription factors and ending up with sets of up- or down-regulated target genes. Since PathoPath and PathoDB (our database on mutated transcription factors and gene regulatory regions [1]) are parts of the whole system, the influence of pathological genetic aberrations can be included in this modeling as well.

REFERENCES

  1. Wingender, E., Chen, X., Fricke, E., Geffers, R., Hehl, R., Liebich, I., Krull, M., Matys, V., Michael, H., Ohnhäuser, R., Prüß, M., Schacherer, F., Thiele, S. and Urbach, S. (2001). The TRANSFAC system on gene expression regulation. Nucleic Acids Res. 29, 281-283.
  2. F. Schacherer, C. Choi, U. Götze, M. Krull, S. Pistor and E. Wingender (2001) "The TRANSPATH signal transduction database: a knowledge base on signal transduction Networks" Bioinformatics, in press.