Rule-Based Modeling and Simulation for Beginners: Intuitive Graphical Interface within Virtual Cell

Abstract

Rule-based modeling approach is invaluable when a number of possible species and reactions in a model becomes too large to allow convenient manual specification. It provides a model description that is capable of accounting for all the potential molecular complexes and interactions among them that can be generated during a response to a signal without explicit enumeration. In this approach, molecular interactions and their effects are represented in the form of reaction rules that serve as generators of molecular species and reactions. Despite powerful descriptive and simulation capabilities, one obstacle to the acceptance of this approach is the lack of user-friendly model specification. Requirement to script rules remains a burden for users of rule-based modeling tools.Here, we present a new graphical user interface for rule-based modeling and simulation. It is integrated into the popular Virtual Cell modeling and simulation framework and allows a classical explicitly specified network model to be combined with a rule-based modeling approach. The interface allows the user to specify and visualize rule-based models without the need to script anything. The extended framework uses BioNetGen (Faeder et al., 2009) and NFSim (Emonet et al., 2011) simulation engines to perform network generation and network-free simulation respectively. Any reaction network model can be enriched by adding a multivalent multistate molecular structure for every species; the resulting model may be simulated as a reaction network using powerful Virtual Cell deterministic and stochastic simulators and protocols. Here we describe the technology underlying rule-based features of Virtual Cell and present an example model that makes use of them.