Section: Application Domains
Participants : Thomas Chatain, Stefan Haar, Serge Haddad, Stefan Schwoon.
We have begun in 2014 to examine concurrency issues in systems biology, and are currently enlarging the scope of our research’s applications in this direction. To see the context, note that in recent years, a considerable shift of biologists’ interest can be observed, from the mapping of static genotypes to gene expression, i.e. the processes in which genetic information is used in producing functional products. These processes are far from being uniquely determined by the gene itself, or even jointly with static properties of the environment; rather, regulation occurs throughout the expression processes, with specific mechanisms increasing or decreasing the production of various products, and thus modulating the outcome. These regulations are central in understanding cell fate (how does the cell differenciate ? Do mutations occur ? etc), and progress there hinges on our capacity to analyse, predict, monitor and control complex and variegated processes. We have applied Petri net unfolding techniques for the efficient computation of attractors in a regulatory network; that is, to identify strongly connected reachability components that correspond to stable evolutions, e.g. of a cell that differentiates into a specific functionality (or mutation). This constitutes the starting point of a broader research with Petri net unfolding techniques in regulation. In fact, ,he use of ordinary Petri nets for capturing regulatory network (RN) dynamics overcomes the limitations of traditional RN models : those impose e.g. Monotonicity properties in the influence that one factor had upon another, i.e. always increasing or always decreasing, and were thus unable to cover all actual behaviours (see ). Rather, we follow the more refined model of boolean networks of automata, where the local states of the different factors jointly detemine which state transitions are possible. For these connectors, ordinary PNs constitute a first approximation, improving greatly over the literature but leaving room for improvement in terms of introducing more refined logical connectors. Future work thus involves transcending this class of PN models. Via unfoldings, one has access – provided efficient techniques are available – to all behaviours of the model, rather than over-or under-approximations as previously. This opens the way to efficiently searching in particular for determinants of the cell fate : which attractors are reachable from a given stage, and what are the factors that decide in favor of one or the other attractor, etc. The list of potential applications in biology and medicine of such a methodology would be too long to reproduce here.