Sequential Reprogramming of Biological Network Fate

Abstract

A major challenge in precision medicine consists in finding the appropriate network rewiring to induce a particular reprogramming of the cell phenotype. The rewiring is caused by specific network action either inhibiting or over-expressing targeted molecules. In some cases, a therapy abides by a time-scheduled drug administration protocol. Furthermore, some diseases are induced by a sequence of mutations leading to a sequence of actions on molecules. In this paper, we extend previous works on abductive-based inference of network reprogramming [3] by investigating the sequential control of Boolean networks. We present a novel theoretical framework and give an upper bound on the size of control sequences as a function of the number of observed variables. We also define an algorithm for inferring minimal parsimonious control sequences allowing to reach a final state satisfying a particular phenotypic property.