Modelling and simulation of the TLR4 pathway with coloured petri nets.

Abstract

This paper demonstrates the first steps of an automation process to develop models of signal transduction pathways using discrete modelling languages. The whole approach consists of modelling, validation, animation, linking databases to simulation tools and also the qualitative analysis of the data. In this paper, we detail the modelling and simulation of the TLR4 pathway with a coloured petri net simulation tool and the validation of this model against the semantic and mechanistic map from a biological database. These graphical maps contain all necessary reactions as a figure. We start with an UML class diagram to understand the static structure of molecules involved in the TLR4 pathway. Afterwards we model and simulate each "pathway step reaction" - one after another - to get the behaviour of the final system. The result is a model of the pathway which can be used in simulations, derived solely from basic chemical reactions in the database. Also, it is a lesson on critical points where human decision-making is needed, because not all the required information is stored directly in the database.