Rules for Modeling Signal-Transduction Systems

This article has a correction Sci. STKE 2006(345):er7

Sci. STKE, 18 July 2006
Vol. 2006, Issue 344, p. re6
DOI: 10.1126/stke.3442006re6

Rules for Modeling Signal-Transduction Systems

  1. William S. Hlavacek1,*,
  2. James R. Faeder2,
  3. Michael L. Blinov3,
  4. Richard G. Posner4,
  5. Michael Hucka5, and
  6. Walter Fontana6
  1. 1Center for Nonlinear Studies, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
  2. 2Theoretical Biology and Biophysics Group, Theoretical Division, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
  3. 3Center for Cell Analysis and Modeling, University of Connecticut Health Center, Farmington, CT 06030, USA.
  4. 4Translational Genomics Research Institute, Phoenix, AZ 85004, USA.
  5. 5Control and Dynamical Systems, California Institute of Technology, Pasadena, CA 91125, USA.
  6. 6Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA.
  1. *Corresponding author. E-mail, wish{at}


Formalized rules for protein-protein interactions have recently been introduced to represent the binding and enzymatic activities of proteins in cellular signaling. Rules encode an understanding of how a system works in terms of the biomolecules in the system and their possible states and interactions. A set of rules can be as easy to read as a diagrammatic interaction map, but unlike most such maps, rules have precise interpretations. Rules can be processed to automatically generate a mathematical or computational model for a system, which enables explanatory and predictive insights into the system’s behavior. Rules are independent units of a model specification that facilitate model revision. Instead of changing a large number of equations or lines of code, as may be required in the case of a conventional mathematical model, a protein interaction can be introduced or modified simply by adding or changing a single rule that represents the interaction of interest. Rules can be defined and visualized by using graphs, so no specialized training in mathematics or computer science is necessary to create models or to take advantage of the representational precision of rules. Rules can be encoded in a machine-readable format to enable electronic storage and exchange of models, as well as basic knowledge about protein-protein interactions. Here, we review the motivation for rule-based modeling; applications of the approach; and issues that arise in model specification, simulation, and testing. We also discuss rule visualization and exchange and the software available for rule-based modeling.


W. S. Hlavacek, J. R. Faeder, M. L. Blinov, R. G. Posner, M. Hucka, and W. Fontana, Rules for Modeling Signal-Transduction Systems. Sci. STKE 2006, re6 (2006).

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