Model checking the evolution of gene regulatory networks

Giacobbe, Mirco and Guet, Cǎlin C and Gupta, Ashutosh K and Henzinger, Thomas A and Paixão, Tiago and Petrov, Tatjana (2016) Model checking the evolution of gene regulatory networks. Acta Informatica. ISSN 1432-0525

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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.

Item Type: Article
DOI: 10.1007/s00236-016-0278-x
Uncontrolled Keywords: model checking, Gene Regulatory Networks, Linear temporal logic, evolutionary biology, Bounded model checking, Classical simulation, Linear constraints, Parameter synthesis, Statistical testing
Subjects: 000 Computer science, knowledge & general works > 000 Computer science, knowledge & systems > 006 Special computer methods
500 Science > 570 Life sciences; biology > 576 Genetics and evolution
Research Group: Barton Group
Guet Group
Henzinger Group
SWORD Depositor: Sword Import User
Depositing User: Sword Import User
Date Deposited: 09 Nov 2016 14:09
Last Modified: 28 Nov 2017 10:15

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