Temporal Reprogramming of Boolean Networks

Cellular reprogramming, a technique that opens huge opportunities in modern and regenerative medicine, heavily relies on identifying key genes to perturb. Most of computational methods focus on finding mutations to apply to the initial state in order to control which attractor the cell will reach. However, it has been shown, and is proved in this article, that waiting between the perturbations and using the transient dynamics of the system allow new reprogramming strategies. To identify these temporal perturbations, we consider a qualitative model of regulatory networks, and rely on Petri nets to model their dynamics and the putative perturbations. Our method establishes a complete characterization of temporal perturbations, whether permanent (mutations) or only temporary, to achieve the existential or inevitable reachability of an arbitrary state of the system. We apply a prototype implementation on small models from the literature and show that we are able to derive temporal perturbations to achieve trans-differentiation.