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

Elena Czeizler, Eugen Czeizler, Bogdan Iancu, Ion Petre, Quantitative Model Refinement as a Solution to the Combinatorial Size Explosion of Biomodels. TUCS Technical Reports 1015, Turku Centre for Computer Science, 2011.

Abstract:

Building a large system through a systematic, step-by-step refinement of an ini-
tial 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 analyze 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 deduced from the original
one. As a case study for this methodology we choose a recently introduced model
for the eukaryotic heat shock response, [15]. 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.

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BibTeX entry:

@TECHREPORT{tCzCzIaPe11a,
  title = {Quantitative Model Refinement as a Solution to the Combinatorial Size Explosion of Biomodels},
  author = {Czeizler, Elena and Czeizler, Eugen and Iancu, Bogdan and Petre, Ion},
  number = {1015},
  series = {TUCS Technical Reports},
  publisher = {Turku Centre for Computer Science},
  year = {2011},
  keywords = {Model refinement, quantitative analysis, heat shock response, acetylation},
  ISBN = {978-952-12-2622-9},
}

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

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