On logical bifurcation diagrams

• Published in: Journal of theoretical biology 2019-04, Vol.466, p.39-63
• Main Authors: Abou-Jaoudé, Wassim, Monteiro, Pedro T.
• Format: Article
• Language: English
• Subjects: Bifurcation diagrams; Hasse diagrams; Life Sciences; Logical modeling; Logical parameters; p53-Mdm2 network; Piecewise-linear differential equations
• ISSN: 0022-5193; 1095-8541
• DOI: 10.1016/j.jtbi.2019.01.008

Bifurcation theory provides a powerful framework to analyze the dynamics of differential systems as a function of specific parameters. Abou-Jaoudé et al. (2009) introduced the concept of logical bifurcation diagrams, an analog of bifurcation diagrams for the logical modeling framework. In this work, we propose a formal definition of this concept. Since logical models are inherently discrete, we use the piecewise differential (PWLD) framework to introduce the underlying bifurcation parameters. Given a regulatory graph, a set of PWLD models is mapped to a set of logical models consistent with this graph, thereby linking continuous changes of bifurcation parameters to sequences of valuations of logical parameters. A logical bifurcation diagram corresponds then to a sequence of valuations of the logical parameters (with their associated set of attractors) consistent with at least one bifurcation diagram of the set of PWLD models. Necessary conditions on logical bifurcation diagrams in the general case, as well as a characterization of these diagrams in the Boolean case, exploiting a partial order between the logical parameters, are provided. We also propose a procedure to determine a logical bifurcation diagram of maximum length, starting from an initial valuation of the logical parameters, in the Boolean case. Finally, we apply our methodology to the analysis of a biological model of the p53-Mdm2 network.