Petri Net-Based Graphical and Computational Modelling of Biological Systems

In silico modelling of biological pathways is a major endeavour of systems biology. Here we present a methodology for construction of pathway models from the literature and other sources using a biologist-friendly graphical modelling system. The pathway notation scheme, called mEPN, is based on the principles of the process diagrams and Petri nets, and facilitates both the graphical representation of complex systems as well as dynamic simulation of their activity. The protocol is divided into four sections: 1) assembly of the pathway in the yEd software package using the mEPN scheme, 2) conversion of the pathway into a computable format, 3) pathway visualisation and in silico simulation using the BioLayout Express 3D software, 4) optimisation of model parameterisation. This method allows reconstruction of any metabolic, signalling and transcriptional pathway as a means of knowledge management, as well as supporting the systems level modelling of their dynamic activity.