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Free keywords:
control strategy, Boolean network, model checking, attractor, phenotype, control
Abstract:
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.
