Recently it has been shown that the control energy required to control a dynamical complex network is prohibitively large when there are only a few control inputs. Most methods to reduce the control energy have focused on where, in the network, to place additional control inputs. Here, in contrast, we show that by controlling the states of a subset of the nodes of a network, rather than the state of every node, while holding the number of control signals constant, the required energy to control a portion of the network can be reduced substantially. The energy requirements exponentially decay with the number of target nodes, suggesting that large networks can be controlled by a relatively small number of inputs as long as the target set is appropriately sized. We validate our conclusions in model and real networks to arrive at an energy scaling law to better design control objectives regardless of system size, energy restrictions, state restrictions, input node choices and target node choices.

Real-world systems in epidemiology, social sciences, power transportation, economics and engineering are often described as multilayer networks. Here we first define and compute the symmetries of multilayer networks, and then study the emergence of cluster synchronization in these networks. We distinguish between independent layer symmetries, which occur in one layer and are independent of the other layers, and dependent layer symmetries, which involve nodes in different layers. We study stability of the cluster synchronous solution by decoupling the problem into a number of independent blocks and assessing stability of each block through a Master Stability Function. We see that blocks associated with dependent layer symmetries have a different structure to the other blocks, which affects the stability of clusters associated with these symmetries. Finally, we validate the theory in a fully analog experiment in which seven electronic oscillators of three kinds are connected with two kinds of coupling.

The effects of molecularly targeted drug perturbations on cellular activities and fates are difficult to predict using intuition alone because of the complex behaviors of cellular regulatory networks. An approach to overcoming this problem is to develop mathematical models for predicting drug effects. Such an approach beckons for co-development of computational methods for extracting insights useful for guiding therapy selection and optimizing drug scheduling. Here, we present and evaluate a generalizable strategy for identifying drug dosing schedules that minimize the amount of drug needed to achieve sustained suppression or elevation of an important cellular activity/process, the recycling of cytoplasmic contents through (macro)autophagy. Therapeutic targeting of autophagy is currently being evaluated in diverse clinical trials but without the benefit of a control engineering perspective. Using a nonlinear ordinary differential equation (ODE) model that accounts for activating and inhibiting influences among protein and lipid kinases that regulate autophagy (MTORC1, ULK1, AMPK and VPS34) and methods guaranteed to find locally optimal control strategies, we find optimal drug dosing schedules (open-loop controllers) for each of six classes of drugs and drug pairs. Our approach is generalizable to designing monotherapy and multi therapy drug schedules that affect different cell signaling networks of interest.

It has recently been shown that the minimum energy solution of the control problem for a linear system produces a control trajectory that is nonlocal. An issue then arises when the dynamics represents a linearization of the underlying nonlinear dynamics of the system where the linearization is only valid in a local region of the state space. Here we provide a solution to the problem of optimally controlling a linearized system by deriving a time-varying set that represents all possible control trajectories parametrized by time and energy. As long as the control action terminus is defined within this set, the control trajectory is guaranteed to be local. If the desired terminus of the control action is far from the initial state, a series of local control actions can be performed in series, relinearizing the dynamics at each new position.

Recently, it has been shown that the control energy required to control a large dynamical complex network is prohibitively large when there are only a few control inputs. Most methods to reduce the control energy have focused on where, in the network, to place additional control inputs. We also have seen that by controlling the states of a subset of the nodes of a network, rather than the state of every node, the required energy to control a portion of the network can be reduced substantially. The energy requirements exponentially decay with the number of target nodes, suggesting that large networks can be controlled by a relatively small number of inputs as long as the target set is appropriately sized. Here, we see that the control energy can be reduced even more if the prescribed final states are not satisfied strictly. We introduce a new control strategy called balanced control for which we set our objective function as a convex combination of two competitive terms: (i) the distance between the output final states at a given final time and given prescribed states and (ii) the total control energy expenditure over the given time period. We also see that the required energy for the optimal balanced control problem approximates the required energy for the optimal target control problem when the coefficient of the second term is very small. We validate our conclusions in model and real networks regardless of system size, energy restrictions, state restrictions, input node choices, and target node choices.