Model checking the evolution of gene regulatory networks

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2017
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Giacobbe, Mirco
Guet, Călin C.
Gupta, Ashutosh
Henzinger, Thomas A.
Paixão, Tiago
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Zusammenfassung

The behaviour of gene regulatory networks (GRNs) is typically analysed using simulation-based statistical testing-like methods. In this paper, we demonstrate that we can replace this approach by a formal verification-like method that gives higher assurance and scalability. We focus on Wagner’s weighted GRN model with varying weights, which is used in evolutionary biology. In the model, weight parameters represent the gene interaction strength that may change due to genetic mutations. For a property of interest, we synthesise the constraints over the parameter space that represent the set of GRNs satisfying the property. We experimentally show that our parameter synthesis procedure computes the mutational robustness of GRNs—an important problem of interest in evolutionary biology—more efficiently than the classical simulation method. We specify the property in linear temporal logic. We employ symbolic bounded model checking and SMT solving to compute the space of GRNs that satisfy the property, which amounts to synthesizing a set of linear constraints on the weights.

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004 Informatik
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Model Check; Linear Temporal Logic; Satisfiability Modulo Theory; Quantifier Elimination Linear Temporal Logic Formula
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ISO 690GIACOBBE, Mirco, Călin C. GUET, Ashutosh GUPTA, Thomas A. HENZINGER, Tiago PAIXÃO, Tatjana PETROV, 2017. Model checking the evolution of gene regulatory networks. In: Acta Informatica. 2017, 54(8), pp. 765-787. ISSN 0001-5903. eISSN 1432-0525. Available under: doi: 10.1007/s00236-016-0278-x
BibTex
@article{Giacobbe2017-12Model-42117,
  year={2017},
  doi={10.1007/s00236-016-0278-x},
  title={Model checking the evolution of gene regulatory networks},
  number={8},
  volume={54},
  issn={0001-5903},
  journal={Acta Informatica},
  pages={765--787},
  author={Giacobbe, Mirco and Guet, Călin C. and Gupta, Ashutosh and Henzinger, Thomas A. and Paixão, Tiago and Petrov, Tatjana}
}
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