Developing executable BioPAX models of gene regulatory networks

Gene regulatory networks (GRNs) are complex, and still largely uncharacterized, sets of regulators and interactions that govern cellular processes, such as proliferation, invasion and metabolic adaptation. Virtually simulating biological pathways offers a powerful method to better understand the role of specific genes and pathways in health and disease, and predict cellular responses to perturbations or treatment. Pathway data collected from the literature is represented computationally in various formats including SBML, SBGN, SIF, to name a few. The BioPAX (Biological Pathway Exchange) language is becoming a widely-used format to work with this data. It aims to offer flexibility and compatibility across computational methods and software to solve the issue of format disagreement from different data providers. Major pathway databases such as Reactome, WikiPathways, and Panther increasingly support file export to BioPAX. Here, we aim to develop executable gene regulatory networks (GRNs) exploiting BioPAX. Having identified all major pathways repositories, we evaluated whether the file formats offered could be executed with available software tools. Whereas we could easily generate faithful visual representations of the GRNs considered, none of the tools available, including BioPAX supported tools, allowed us to efficiently simulate them. As a starting point, we provide a tool which converts BioPAX (.owl) models into GINML files (.ginml), a variant of GXL. These can be read in commonly used simulators like GINSim, offering a user-friendly interface to work and simulate BioPAX models, previously unavailable.