Model checking the evolution of gene regulatory networks Journal Article

Author(s): Giacobbe, Mirco; Guet, Cǎlin C; Gupta, Ashutosh K; Henzinger, Thomas A; Paixão, Tiago; Petrov, Tatjana P
Article Title: Model checking the evolution of gene regulatory networks
Affiliation IST Austria
Abstract: 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.
Keywords: model checking; Gene Regulatory Networks; Linear temporal logic; evolutionary biology; Bounded model checking; Classical simulation; Linear constraints; Parameter synthesis; Statistical testing
Journal Title: Acta Informatica
Volume: 54
Issue 8
ISSN: 1432-0525
Publisher: Springer  
Date Published: 2017-12-01
Start Page: 765
End Page: 787
DOI: 10.1007/s00236-016-0278-x
Notes: This research was supported by the European Research Council (ERC) under Grant 267989 (QUAREM), the Austrian Science Fund (FWF) under Grants S11402-N23 (RiSE) and Z211-N23 (Wittgenstein Award), the European Union’s SAGE Grant Agreement No. 618091, ERC Advanced Grant ERC-2009-AdG-250152, the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007-2013) under REA Grant Agreement No. 291734, and the SNSF Advanced Postdoc.Mobility Fellowship, the Grant Number P300P2_161067. Open access funding provided by Institute of Science and Technology (IST Austria).
Open access: yes (OA journal)
IST Austria Authors
  1. Thomas A. Henzinger
    415 Henzinger
  2. Călin Guet
    31 Guet
  3. Tiago Paixão
    27 Paixão
  4. Ashutosh Gupta
    16 Gupta
  5. Tatjana Petrov
    12 Petrov
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