Multi-scale, multi-resolution brain cancer modeling

In advancing discrete-based computational cancer models towards clinical applications, one faces the dilemma of how to deal with an ever growing amount of biomedical data that ought to be incorporated eventually in one form or another. Model scalability becomes of paramount interest. In an effort to start addressing this critical issue, here, we present a novel multi-scale and multi-resolution agent-based in silico glioma model. While 'multi-scale' refers to employing an epidermal growth factor receptor (EGFR)-driven molecular network to process cellular phenotypic decisions within the micro-macroscopic environment, 'multi-resolution' is achieved through algorithms that classify cells to either active or inactive spatial clusters, which determine the resolution they are simulated at. The aim is to assign computational resources where and when they matter most for maintaining or improving the predictive power of the algorithm, onto specific tumor areas and at particular times. Using a previously described 2D brain tumor model, we have developed four different computational methods for achieving the multi-resolution scheme, three of which are designed to dynamically train on the high-resolution simulation that serves as control. To quantify the algorithms' performance, we rank them by weighing the distinct computational time savings of the simulation runs versus the methods' ability to accurately reproduce the high-resolution results of the control. Finally, to demonstrate the flexibility of the underlying concept, we show the added value of combining the two highest-ranked methods. The main finding of this work is that by pursuing a multi-resolution approach, one can reduce the computation time of a discrete-based model substantially while still maintaining a comparably high predictive power. This hints at even more computational savings in the more realistic 3D setting over time, and thus appears to outline a possible path to achieve scalability for the all-important clinical translation.