Control in Boolean Networks With Model Checking

Understanding control mechanisms in biological systems plays a crucial role in important applications, for instance in cell reprogramming. Boolean modeling allows the identification of possible efficient strategies, helping to reduce the usually high and time-consuming experimental efforts. Available approaches to control strategy identification usually focus either on attractor or phenotype control, and are unable to deal with more complex control problems, for instance phenotype avoidance. They also fail to capture, in many situations, all possible minimal strategies, finding instead only sub-optimal solutions. In order to fill these gaps, we present a novel approach to control strategy identification in Boolean networks based on model checking. The method is guaranteed to identify all minimal control strategies, and provides maximal flexibility in the definition of the control target. We investigate the applicability of the approach by considering a range of control problems for different biological systems, comparing the results, where possible, to those obtained by alternative control methods.