A seven-step guide to spatial, agent-based modelling of tumour evolution.

Abstract

Spatial agent-based models are frequently used to investigate the evolution of solid tumours subject to localized cell-cell interactions and microenvironmental heterogeneity. As spatial genomic, transcriptomic and proteomic technologies gain traction, spatial computational models are predicted to become ever more necessary for making sense of complex clinical and experimental data sets, for predicting clinical outcomes, and for optimizing treatment strategies. Here we present a non-technical step by step guide to developing such a model from first principles. Stressing the importance of tailoring the model structure to that of the biological system, we describe methods of increasing complexity, from the basic Eden growth model up to off-lattice simulations with diffusible factors. We examine choices that unavoidably arise in model design, such as implementation, parameterization, visualization and reproducibility. Each topic is illustrated with examples drawn from recent research studies and state of the art modelling platforms. We emphasize the benefits of simpler models that aim to match the complexity of the phenomena of interest, rather than that of the entire biological system. Our guide is aimed at both aspiring modellers and other biologists and oncologists who wish to understand the assumptions and limitations of the models on which major cancer studies now so often depend.