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A Boolean Approach for Disentangling the Numerical Contribution of Modules to the System-Level Behavior of a Biomodel

Elena Czeizler, Andrzej Mizera, Ion Petre, A Boolean Approach for Disentangling the Numerical Contribution of Modules to the System-Level Behavior of a Biomodel. TUCS Technical Reports 997, Turku Centre for Computer Science, 2011.

Abstract:

To disentangle the numerical contribution of modules to the system-level behavior of a given biomodel, one often considers knockdown mutant models, investigating the change in the model behavior when modules are systematically included and excluded from the model architecture in all possible ways. We propose in this paper a Boolean logic-based approach for extracting conclusions about the role of each module from the systematic comparison of the numerical behavior of all knockdown mutants. We associate a Boolean variable to each module, expressing when the module is included in the architecture (value `true') and when it is not (value `false'). We can then express the satisfiability of system-level properties of the full model, such as efficiency, or economical use of resources, in terms of a Boolean formula expressing in a compact way which model architectures, i.e., which combinations of modules, give rise to the desired property. We demonstrate this methodology on a recently proposed computational model for the heat shock response in eukaryotes. We describe the contribution of each of its three feedback loops towards achieving an economical and effective heat shock response. The applicability of our approach is more general: the same method could be applied to describe how properties of a wet-lab biomodel emerge from the combination of its modules. In this case, one would simply replace the numerical simulation of the computational models with the experimental measurement of the behavior of the wet-lab biomodel and that of its knockdown mutant variants.

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BibTeX entry:

@TECHREPORT{tCzMiPe11a,
  title = {A Boolean Approach for Disentangling the Numerical Contribution of Modules to the System-Level Behavior of a Biomodel},
  author = {Czeizler, Elena and Mizera, Andrzej and Petre, Ion},
  number = {997},
  series = {TUCS Technical Reports},
  publisher = {Turku Centre for Computer Science},
  year = {2011},
  keywords = {mathematical model, modularization, Boolean logic, heat shock response},
  ISBN = {978-952-12-2544-4},
}

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

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