Innovations of the Rule-Based Modeling Approach

  • Lily A. Chylek
  • Edward C. Stites
  • Richard G. Posner
  • William S. Hlavacek


New modeling approaches are needed to tackle the complexity of cell signaling systems. An emerging approach is rule-based modeling, in which protein-protein interactions are represented at the level of functional components. By using rules to represent interactions, a modeler can avoid enumerating the reachable chemical species in a system, which is a necessity in traditional modeling approaches. A set of rules can be used to generate a reaction network, or to perform simulations with or without network generation. Although the rule-based approach is a relatively recent development in biology, it is based on concepts that have proven useful in other fields. In this chapter, we discuss innovations of the rule-based modeling approach, relative to traditional approaches for modeling chemical kinetics. These innovations include the use of rules to concisely capture the dynamics of molecular interactions, the view of models as programs, and agent-based computational approaches that can be applied to simulate the chemical kinetics of a system characterized by a large traditional model. These innovations should enable the development of models that can relate the molecular state of a cell to its phenotype, even though vast and complex networks bridge perturbations at the molecular level to fates and activities at the cellular level. In the future, we expect that validated rule-based models will be useful for model-guided studies of cell signaling mechanisms, interpretation of temporal phosphoproteomic data, and cell engineering applications.


Computational modeling Combinatorial complexity Protein-protein interactions Cell signaling Rule-based modeling Formal languages Simulation algorithms Chemical kinetics 



Bond electron matrix


BioNetGen Language


Ordinary differential equation


Systems Biology Graphical Notation


Systems Biology Markup Language



We thank Michael L. Blinov, James R. Faeder, David J. Klinke II, Jean Krivine, and Carlos F. Lopez for helpful discussions.


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Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Lily A. Chylek
    • 1
  • Edward C. Stites
    • 2
  • Richard G. Posner
    • 2
    • 3
  • William S. Hlavacek
    • 4
    • 5
  1. 1.Department of Chemistry and Chemical BiologyCornell UniversityIthacaUSA
  2. 2.Clinical Translational Research DivisionTranslational Genomics Research InstitutePhoenixUSA
  3. 3.Department of Biological SciencesNorthern Arizona UniversityFlagstaffUSA
  4. 4.Department of BiologyUniversity of New MexicoAlbuquerqueUSA
  5. 5.Theoretical Biology and Biophysics Group, Theoretical DivisionLos Alamos National LaboratoryLos Alamos USA

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