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Title: SigNetRouter - Computer Program for Detecting the Routes between Factors and Targets in Signaling Networks
P187
Zevedei-Oancea, Ionela; Schuster, Stefan

zevedei@mdc-berlin.de
Max Delbrück Center for Molecular Medicine

The maps describing signaling pathways are usually very complicated. They may contain simple activations as "A activates B", but also multipart activation as "A and B need to present simultaneously to activate C". Frequently, also biochemical reactions converting substrates into products are involved in these processes. These have to be treated differently because the reactants disappear while an activator is still in the system after it did its job. Furthermore, since cycles can occur it can be difficult to understand how signal transmission works. One question could be which factor influences which target and on which route. Overexpression or inhibition of some enzymes can increase or decrease, respectively, the effect of the route(s) involving these enzymes. Furthermore, one may be interested in identifying the cycles. The idea is somehow similar to that of elementary flux modes for metabolic systems, for the identification of which there are already several programs. One of them is METATOOL, which was developed in our group.

We developed an application, called SigNetRouter, in C++ for detecting routes in signaling networks. It requires, as input file, a simple text file in which one can make the difference between activations and reactions. Several such sections could alternate. Comments are also allowed, in the style of C++ programming. The activations and reactions are considered as irreversible. A reaction or activation can be written on several lines. If mistakes occur, the program will report the error and its type and will request the user to review the input file. Otherwise, the program captures the information and processes it in accordance to the orders that the user gives.

The possible commands are gathered in a menu. One can give a new text file as input file and set the output file. There are two such files declared by default and they can be used as an example. One can find a classification of metabolites in factors, targets, and intermediaries. It is very unlikely that a factor can work on its own. The factors that could support it are given in the output. The same is valid for targets. Also other targets may be influenced when only one is directly envisaged at the beginning. They are also displayed. One can view the routes on which a factor affects some targets and which are the targets. Conversely, also the factors which influence a given target and their routes are found. Cycles that occur in between are detected. Some theoretical and biological examples are given to illustrate the features of the program.