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Quantitative Model Refinement in Four Different Frameworks, with Applications to the Heat Shock Response

Diana-Elena Gratie, Bogdan Iancu, Sepinoud Azimi, Ion Petre, Quantitative Model Refinement in Four Different Frameworks, with Applications to the Heat Shock Response. TUCS Technical Reports 1067, TUCS, 2013.

Abstract:

When compiling a biological model, one often starts with an abstract representation, that is subsequently refined through several consecutive steps to incorporate more details regarding various reactants and/or reactions. To avoid the computationally expensive refitting of the model after each refinement step, the new parameters should be set so that the numerical behavior of the initial model is preserved. The iterative process of adding details to a model while preserving its numerical behavior is called quantitative model refinement, and it has been previously discussed for ODE-based models and for kappa-based models. In this paper, we investigate and compare this approach in four modeling frameworks: ordinary differential equations, rule-based modeling, Petri nets and guarded command languages. As case study we use a model for the eukaryotic heat shock response that we refine to include the acetylation of one molecule. We discuss how to perform the refinement in each of these frameworks in order to avoid the combinatorial state explosion of the refined model. We conclude that Bionetgen (and rule-based modeling in general) is well-suited for a compact representation of the refined model, Petri nets offer a good solution through the use of colors, while the PRISM refined model may be much larger than the basic model.

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BibTeX entry:

@TECHREPORT{tAzGrIaPe13a,
  title = {Quantitative Model Refinement in Four Different Frameworks, with Applications to the Heat Shock Response},
  author = {Gratie, Diana-Elena and Iancu, Bogdan and Azimi, Sepinoud and Petre, Ion},
  number = {1067},
  series = {TUCS Technical Reports},
  publisher = {TUCS},
  year = {2013},
  keywords = {Quantitative model refinement, heat shock response, acetylation, rule-based modeling, Petri nets, model checking.},
  ISBN = {978-952-12-2622-9},
}

Belongs to TUCS Research Unit(s): Computational Biomodeling Laboratory (Combio Lab)

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