DiSH Simulator: Capturing Dynamics of Cellular Signaling with Heterogeneous Knowledge

Abstract

We present DiSH-Sim, 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. We focus on order of update and thus incorporate information about timing, taking into account that biological processes are not synchronized and certain biochemical changes occur slower than others. Another feature of our simulator is the use of grouped rules to model multi-valued elements and delays. The DiSH-Sim is publicly available and is being used to validate discrete cancer microenvironment and infectious disease models. It is also incorporated within a large architecture that includes natural language processing tools that read biological literature to assemble logical models. This paper demonstrates the functionalities and ease of use of DiSH-Sim, making it a very useful tool for discrete modeling.