JAK/STAT signalling - an executable model assembled from molecule-centred modules demonstrating a module-oriented database concept for systems- and synthetic biology

Abstract

We describe a molecule-oriented modelling approach based on a collection of Petri net models organized in the form of modules into a prototype database accessible through a web interface. The JAK/STAT signalling pathway with the extensive cross-talk of its components is selected as case study. Each Petri net module represents the reactions of an individual protein with its specific interaction partners. These Petri net modules are graphically displayed, can be executed individually, and allow the automatic composition into coherent models containing an arbitrary number of molecular species chosen ad hoc by the user. Each module contains metadata for documentation purposes and can be extended to a wiki-like minireview. The database can manage multiple versions of each module. It supports the curation, documentation, version control, and update of individual modules and the subsequent automatic composition of complex models, without requiring mathematical skills. Modules can be (semi-) automatically recombined according to user defined scenarios e.g. gene expression patterns in given cell types, under certain physiological conditions, or states of disease. Adding a localisation component to the module database would allow to simulate models with spatial resolution in the form of coloured Petri nets. As synthetic biology application we propose the fully automated generation of synthetic or synthetically rewired network models by composition of metadata-guided automatically modified modules representing altered protein binding sites. Petri nets composed from modules can be executed as ODE system, stochastic, hybrid, or merely qualitative models and exported in SMBL format.