Concurrency in Biological Modeling: Behavior, Execution and Visualization

Modeling natural systems is a complicated task that involves the concurrent behavior of various processes, mechanisms and objects. Here, we describe an approach that we have been taking in our group for several years, whereby the complexity of the problem is reduced by decomposing a natural system into its basic elements, which are then reassembled and combined to form a comprehensive, simulatable model of the system. Our modeling approach allows one to view a natural system at various levels of abstraction, in a way that makes it possible to zoom in and out between levels. Using statecharts, a high level visual formalism, we specify the behavior of the basic elements of each level and compile these into executable code, which is then linked to an animated front-end. At run-time, the concurrent execution of the basic elements is continuously displayed and provides a dynamic description of the system. We illustrate this approach by modeling aspects of three biological systems: development of the mammalian pancreas; the differentiation of T cells in the thymus; and the dynamic architecture of a lymph node. We compared each model's behavior with experimental data and also reproduced genetic experiments in silico. Interestingly, certain behavioral properties that were not explicitly programmed into the model emerge from concurrent execution and correspond well with the experimental observations.