Quantitative Model Refinement as a Solution to the Combinatorial Size Explosion of Biomodels

  • Authors:

  • Elena Czeizler;Eugen Czeizler;Bogdan Iancu;Ion Petre

  • Affiliations:

  • Research Programs Unit, Genome-Scale Biology, Faculty of Medicine, University of Helsinki FI-00014 Helsinki, Finland;Department of Information and Computer Science, Aalto University School of Science FI-00076 Aalto, Finland;Computational Biomodelling Laboratory, íbo Akademi University and Turku Centre for Computer Science FI-20520 Turku, Finland;Computational Biomodelling Laboratory, íbo Akademi University and Turku Centre for Computer Science FI-20520 Turku, Finland

  • Venue:
  • Electronic Notes in Theoretical Computer Science (ENTCS)
  • Year:
  • 2012

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Abstract

Building a large system through a systematic, step-by-step refinement of an initial abstract specification is a well established technique in software engineering, not yet much explored in systems biology. In the case of systems biology, one starts from an abstract, high-level model of a biological system and aims to add more and more details about its reactants and/or reactions, through a number of consecutive refinement steps. The refinement should be done in a quantitatively correct way, so that (some of) the numerical properties of the model (such as the experimental fit and validation) are preserved. In this study, we focus on the data-refinement mechanism where the aim is to increase the level of details of some of the reactants of a given model. That is, we analyse the case when a model is refined by substituting a given species by several types of subspecies. We show in this paper how the refined model can be systematically obtained from the original one. As a case study for this methodology we choose a recently introduced model for the eukaryotic heat shock response, [I. Petre, A. Mizera, C. L. Hyder, A. Meinander, A. Mikhailov, R.I. Morimoto, L. Sistonen, J. E. Eriksson, R.-J. Back, A simple mass-action model for the eukaryotic heat shock response and its mathematical validation, Natural Computing, 10(1), 595-612, 2011.]. We refine this model by including details about the acetylation of the heat shock factors and its influence on the heat shock response. The refined model has a significantly higher number of kinetic parameters and variables. However, we show that our methodology allows us to preserve the experimental fit/validation of the model with minimal computational effort.