A Computational Approach to Studying the Processes Active During Helicobacter hepaticus-Induced Intestinal Inflammation

Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastro-intestinal tract that usually manifests as either ulcerative colitis or Crohn's disease. Helicobacter hepaticus (Hh)-induced colitis is a mouse model of intestinal inflammation whereby IL-10 knock out mice are infected with Hh, resulting in pathology similar to that seen in Crohn's disease.

Following the Complex Systems Modelling and Simulation (CoSMoS) process, a principled approach to the engineering of simulations of complex systems, we have developed IBDSim, a computational model of the processes active in the intestinal tract during Hh-induced colitis. IBDSim is a hybrid agent-based model (ABM) that combines agent-based modelling with systems biology and quantitative systems pharmacology approaches, to capture both cell- and system-level behaviours. In combining these approaches, the Automated Simulation Parameter Alteration and SensItivity Analysis toolkit (ASPASIA) was developed to aid in the calibration and analysis of models written in Systems Biology Mark-up Language (SBML), where the addition of an intervention is required for key behaviours to emerge. SBML models generated using this toolkit could then be incorporated into IBDSim.