Rule-Based Modeling with BioNetGen and RuleBender

Rule-based modeling involves the representation of molecules as structured objects and molecular interactions as rules for transforming the attributes of these objects. The approach allows systematic incorporation of site-specific details about protein-protein interactions into a model for the dynamics of cell regulatory networks, including processes involving cell signaling, gene regulation, and metabolism. The consequences of protein-protein interactions are difficult to specify and track with a conventional modeling approach because of the large number of protein phosphoforms and protein complexes that these interactions potentially generate. Here, we demonstrate how a rule-based model is specified in the BioNetGen language (BNGL) using the RuleBender interface and demonstrate how models can be visualized, simulated, and analyze. We also discuss new developments in rule-based modeling that should enable the construction and analysis of comprehensive models for signal transduction pathways.

John Sekar, Jose Juan Tapia, Robert P. Sheehan, Yang Yang, and James R. Faeder

Department of Computational and Systems Biology, University of Pittsburgh School of Medicine