Systems biology at the giga-scale: Large multiscale models of complex, heterogeneous multicellular systems

Agent-based modelling has proven its usefulness in several biomedical projects by explaining and uncovering mechanisms in diseases. Nevertheless, the scenarios addressed in these models usually consider a small number of cells, lack cell-specific characterisation and dynamic interactions and have a simplistic environment description. Tools that enable scalable, real-sized simulations of biological systems that require complex setups are needed to have simulations closer to biomedical scenarios that can capture cell-to-cell heterogeneity and system-wide emerging properties. To deliver simulations at the giga-scale (10⁹ cells), different tools have implemented technologies to run in high-performance computing clusters. We hereby review these efforts and detail the main areas of improvement the field needs to focus on to have simulations that are a step closer to having digital twins.