Agent-based modelling (ABM) offers a framework to realistically couple subcellular signaling pathways to cellular behavior and macroscopic tissue organization. However, these models have been previously inaccessible to many systems biologists due to the difficulties with formulating and simulating multi-scale behavior. In this chapter, a review of the Compucell3D framework is presented along with a general workflow for transitioning from a well-mixed ODE model to an ABM. These techniques are demonstrated through a case study on the simulation of a Notch-Delta Positive Feedback, Lateral Inhibition (PFLI) gene circuit in the intestinal crypts. Specifically, techniques for gene circuit-driven hypothesis formation, geometry construction, selection of simulation parameters, and simulation quantification are presented.
Keywords: Agent-based modelling; Biological control mechanisms; Cell fate differentiation; Multi-scale modelling; Stem cell niche.