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

摘要

We describe a molecule-oriented modelling approach based on a collection ofPetri net models organized in the form of modules into a prototype databaseaccessible through a web interface. The JAK/STAT signalling pathway with theextensive cross-talk of its components is selected as case study. Each Petrinet module represents the reactions of an individual protein with its specificinteraction partners. These Petri net modules are graphically displayed, can beexecuted individually, and allow the automatic composition into coherent modelscontaining an arbitrary number of molecular species chosen ad hoc by the user.Each module contains metadata for documentation purposes and can be extended toa wiki-like minireview. The database can manage multiple versions of eachmodule. It supports the curation, documentation, version control, and update ofindividual modules and the subsequent automatic composition of complex models,without requiring mathematical skills. Modules can be (semi-) automaticallyrecombined according to user defined scenarios e.g. gene expression patterns ingiven cell types, under certain physiological conditions, or states of disease.Adding a localisation component to the module database would allow to simulatemodels with spatial resolution in the form of coloured Petri nets. As syntheticbiology application we propose the fully automated generation of synthetic orsynthetically rewired network models by composition of metadata-guidedautomatically 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.