The Transpath Signal Transduction Database

F. Schacherer and E. Wingender




Gesellschaft für Biotechnologische Forschung mbH
Mascheroder Weg 1
D­38124 Braunschweig
Phone: +49­531­6181 428
Fax: +49­531­6181 266
E-mail: frs@gbf.de






INTRODUCTION

Cells, especially those of a complex multicellular organism, have to act and react to each other and to external influences in a well concerted manner. Thus, if we want to understand cellular behaviour and its responses to external signals, or want to influence it in a predictable manner, we have to understand the pathways through which these signals are mediated into and within the cell. Knowledge about the principle mechanisms of signal transduction and regulation mechanisms of individual macromolecules in signaling pathways has multiplied in the last decade. It is now growing at a rate that makes it difficult to keep up with [Krauss, 1997]. In most cases changes in cell behaviour involve the execution of transcriptional events, which are specific for each signal in its cellular context [Hill and Treisman, 1995]. Biological signaling pathways also interact with each other to form complex networks. These networks show emergent properties like signal integration accross multiple time scales or self­sustaining feedback loops, which are not present in the isolated pathways [Bhalla and Iyengar, 1999].


TRANSPATH

The huge and ever more rapid growing amount of signal transduction data demands for a database that stores and organizes this knowledge, providing simple and fast access to the information. The complexity created by the cross­talk between pathways makes it virtually impossible to infer by hand all the consequences that follow after one modifies one part of the network. To this end, computer­aided simulation will have to be used. It can only be successful on the basis of a comprehensive and detailed dataset. At the moment, there are at least two databases providing information on signal transduction in general which are publicly available world­wide, CSNDB and KEGG. CSNDB (http://geo.nihs.go.jp/csndb.html) specializes in the semantic view of signaling pathways, incorporating a pathway viewer [Takai­Igarashi and Kaminuma, 1998]. KEGG (http://www.genome.ad.jp/kegg/kegg.html) focuses on metabolic pathways, but also contains some signal pathways. These consist of maps of interacting molecules or genes. The signal pathways do not contain data on the reaction mechanisms. [Ogata et al., 1998]. TRANSPATH (http://transpath.gbf.de) is an information system on gene regulatory pathways, and a member of the TRANSFAC family of databases [Heinemeyer et. al., 1999]. The core functionality of the information system is to provide a structured repository for pathway­related data. Also the data should be fit to be used in signaling network simulations. TRANSPATH focuses on pathways involved in the regulation of transcription factors in different mammalian species, mainly human, mouse and rat, but aims at a comprehensive data collection. Elements of the relevant signal transduction pathways like hormones, receptors, enzymes and transcription factors are persistently stored together with information about their interaction and references in an object­oriented database. Objects are a natural choice to represent those elements as data. Molecules with similar structure and function can be grouped in families, providing a way to abstract their common signaling behaviour. Interactions are modeled as reactions with reactants and products and a single enzyme. To enable the system to be used as the basis for simulation it is neccesary to include rate constants in the reactions and different entries for different states of a molecule. Alternatively to this mechanistic view, interactions can be stored as activation and inhibition pointers providing a semantic view (similar to that provided by CSNDB) which corresponds to the schematic drawings familiar from the literature. Queries to the database are conducted via the Internet by submitting names of transcription factors or other signal molecules. The user can choose to view either the encyclopaedic information for the requested molecule or the reaction cascades starting from the molecule. All information is validated with references to the original publications. Also, references to other databases are provided (TRANSFAC, CYTOMER, SwissProt, EMBL, PubMed and CSNDB). The TRANSPATH interface has also been used as a gateway to the CSNDB data.


ACKNOWLEDGEMENT

This work has been supported by a grant of the German Ministry of Education, Science, Research and Technology (BMBF; 01 KW 9629/7). The complete data set of CSNDB was generously provided by T. Takai­Igarashi.


REFERENCES