A Hybrid Simulation Model for Studying Acute Inflammatory Response

The modeling of complex biological systems presents a significant challenge. Central to this challenge is striking a balance between the degree of abstraction required to facilitate analysis and understanding, and the degree of comprehensiveness required for fidelity of the model to its reference-system. It is likely necessary to utilize multiple modeling methods in order to achieve this balance. Our research created a hybrid simulation model by melding an agent-based model of acute local infection with a system dynamics model that reflects key systemic properties. The agent based model was originally developed to simulate global inflammation in response to injury or infection, and has been used to simulate clinical drug trials. The long term objective is to develop models than can be scaled up to represent organ and system level phenomena such as multiple organ failure associated with severe sepsis. The work described in this paper is an initial proof of concept of the ability to combine these two modeling methods into a hybrid model, the type of which will almost certainly be needed to accomplish the ultimate objective of comprehensive in silico research platforms