Model checking gene regulatory networks Conference Paper

Author(s): Giacobbe, Mirco; Guet, Cǎlin C; Gupta, Ashutosh K; Henzinger, Thomas A; Paixão, Tiago; Petrov, Tatjana P
Title: Model checking gene regulatory networks
Title Series: LNCS
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 logics. 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: Gene Regulatory Networks; Linear temporal logic; evolutionary biology; Bounded model checking; Classical simulation; Linear constraints; Parameter synthesis; Statistical testing
Conference Title: TACAS: Tools and Algorithms for the Construction and Analysis of Systems
Volume: 9035
Conference Dates: April 11-18, 2015
Conference Location: London, UK
Publisher: Springer  
Date Published: 2015-04-01
Start Page: 469
End Page: 483
DOI: 10.1007/978-3-662-46681-0_47
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 Early Postdoc.Mobility Fellowship, the grant number P2EZP2 148797.
Open access: yes (repository)
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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