On circuit functionality in Boolean networks.

It has been proved, for several classes of continuous and discrete dynamical systems, that the presence of a positive (resp. negative) circuit in the interaction graph of a system is a necessary condition for the presence of multiple stable states (resp. a cyclic attractor). A positive (resp. negative) circuit is said to be functional when it "generates" several stable states (resp. a cyclic attractor). However, there are no definite mathematical frameworks translating the underlying meaning of "generates." Focusing on Boolean networks, we recall and propose some definitions concerning the notion of functionality along with associated mathematical results.

"Immunetworks", intersecting circuits and dynamics.

This paper proposes a study of biological regulation networks based on a multi-level strategy. Given a network, the first structural level of this strategy consists in analysing the architecture of the network interactions in order to describe it. The second dynamical level consists in relating the patterns found in the architecture to the possible dynamical behaviours of the network. It is known that circuits are the patterns that play the most important part in the dynamics of a network in the sense that they are responsible for the diversity of its asymptotic behaviours. Here, we pursue further this idea and argue that beyond the influence of underlying circuits, intersections of circuits also impact significantly on the dynamics of a network and thus need to be payed special attention to. For some genetic regulation networks involved in the control of the immune system ("immunetworks"), we show that the small number of attractors can be explained by the presence, in the underlying structures of these networks, of intersecting circuits that "inter-lock".

Robustness in regulatory interaction networks. A generic approach with applications at different levels: physiologic, metabolic and genetic.

Regulatory interaction networks are often studied on their dynamical side (existence of attractors, study of their stability). We focus here also on their robustness, that is their ability to offer the same spatiotemporal patterns and to resist to external perturbations such as losses of nodes or edges in the networks interactions architecture, changes in their environmental boundary conditions as well as changes in the update schedule (or updating mode) of the states of their elements (e.g., if these elements are genes, their synchronous coexpression mode versus their sequential expression). We define the generic notions of boundary, core, and critical vertex or edge of the underlying interaction graph of the regulatory network, whose disappearance causes dramatic changes in the number and nature of attractors (e.g., passage from a bistable behaviour to a unique periodic regime) or in the range of their basins of stability. The dynamic transition of states will be presented in the framework of threshold Boolean automata rules. A panorama of applications at different levels will be given: brain and plant morphogenesis, bulbar cardio-respiratory regulation, glycolytic/oxidative metabolic coupling, and eventually cell cycle and feather morphogenesis genetic control.

Attraction basins as gauges of robustness against boundary conditions in biological complex systems.

One fundamental concept in the context of biological systems on which researches have flourished in the past decade is that of the apparent robustness of these systems, i.e., their ability to resist to perturbations or constraints induced by external or boundary elements such as electromagnetic fields acting on neural networks, micro-RNAs acting on genetic networks and even hormone flows acting both on neural and genetic networks. Recent studies have shown the importance of addressing the question of the environmental robustness of biological networks such as neural and genetic networks. In some cases, external regulatory elements can be given a relevant formal representation by assimilating them to or modeling them by boundary conditions. This article presents a generic mathematical approach to understand the influence of boundary elements on the dynamics of regulation networks, considering their attraction basins as gauges of their robustness. The application of this method on a real genetic regulation network will point out a mathematical explanation of a biological phenomenon which has only been observed experimentally until now, namely the necessity of the presence of gibberellin for the flower of the plant Arabidopsis thaliana to develop normally.