DiSH simulator: Capturing dynamics of cellular signaling with heterogeneous knowledge

In this paper, we present DiSH, a simulator for large discrete models of biological signal transduction pathways, capable of simulating networks with multi-valued elements in both deterministic and stochastic manner. The simulator incorporates the timing of molecular reactions, which are often not synchronized and occur in random order, and it also takes into account the difference between slow and fast reactions. DiSH also allows for changes in conditions during simulations, combined deterministic and stochastic changes, and it uses the concept of delays in models, similar to delays in digital circuits. DiSH is publicly available and has been used to study intra- and inter-cellular models of several diseases. It is also being used as part of a larger architecture including natural language processing tools that read biological literature, automated model assembly tools, and formal model analysis tools.