Dynamical methods for target control of biological networks

Estimating the influence that individual nodes have on one another in a Boolean network is essential to predict and control the system's dynamical behaviour, for example, detecting key therapeutic targets to control pathways in models of biological signalling and regulation. Exact estimation is generally not possible due to the fact that the number of configurations that must be considered grows exponentially with the system size. However, approximate, scalable methods exist in the literature. These methods can be divided into two main classes: (i) graph-theoretic methods that rely on representations of Boolean dynamics into static graphs and (ii) mean-field approaches that describe average trajectories of the system but neglect dynamical correlations. Here, we compare systematically the performance of these state-of-the-art methods on a large collection of real-world gene regulatory networks. We find comparable performance across methods. All methods underestimate the ground truth, with mean-field approaches having a better recall but a worse precision than graph-theoretic methods. Computationally speaking, graph-theoretic methods are faster than mean-field ones in sparse networks, but are slower in dense networks. The preference of which method to use, therefore, depends on a network's connectivity and the relative importance of recall versus precision for the specific application at hand.