Classification of transient behaviours in a time-dependent toggle switch model

Verd Fernández, Berta, 1984-; Crombach, Anton; Jaeger, Johannes, 1973-

doi:http://dx.doi.org/10.1186/1752-0509-8-43

Classification of transient behaviours in a time-dependent toggle switch model

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Verd B, Crombach A, Jaeger J. Classification of transient behaviours in a time-dependent toggle switch model. BMC Systems Biology. 2014; 8: 43. DOI 10.1186/1752-0509-8-43

Abstract

Background: Waddington’s epigenetic landscape is an intuitive metaphor for the developmental and evolutionary potential of biological regulatory processes. It emphasises time-dependence and transient behaviour. Nowadays, we can derive this landscape by modelling a specific regulatory network as a dynamical system and calculating its so-called potential surface. In this sense, potential surfaces are the mathematical equivalent of the Waddingtonian landscape metaphor. In order to fully capture the time-dependent (non-autonomous) transient behaviour of biological processes, we must be able to characterise potential landscapes and how they change over time. However, currently available mathematical tools focus on the asymptotic (steady-state) behaviour of autonomous dynamical systems, which restricts how biological systems are studied. Results: We present a pragmatic first step towards a methodology for dealing with transient behaviours in non-autonomous systems. We propose a classification scheme for different kinds of such dynamics based on the simulation of a simple genetic toggle-switch model with time-variable parameters. For this low-dimensional system, we can calculate and explicitly visualise numerical approximations to the potential landscape. Focussing on transient dynamics in non-autonomous systems reveals a range of interesting and biologically relevant behaviours that would be missed in steady-state analyses of autonomous systems. Our simulation-based approach allows us to identify four qualitatively different kinds of dynamics: transitions, pursuits, and two kinds of captures. We describe these in detail, and illustrate the usefulness of our classification scheme by providing a number of examples that demonstrate how it can be employed to gain specific mechanistic insights into the dynamics of gene regulation. Conclusions: The practical aim of our proposed classification scheme is to make the analysis of explicitly time-dependent transient behaviour tractable, and to encourage the wider use of non-autonomous models in systems biology. Our method is applicable to a large class of biological processes.