Target Control in Logical Models using Domain of Influence of nodes*

Dynamical models of biological networks are used to understand the underlying mechanisms of complex diseases and to design therapeutic strategies. Network control problems, and especially target control, are a promising avenue toward developing disease therapies. In target control it is assumed that a small subset of nodes is most relevant to the system’s state and the goal is to drive the target nodes into their desired states. An example of target control would be driving a cell to commit to apoptosis. From the experimental perspective, gene knockout, pharmacological inhibition of proteins and providing sustained external signals are among practical intervention techniques. We propose to use the stabilizing effect of sustained interventions in logical models to solve this problem in biological networks, especially signal transduction networks. Specifically, we define the domain of influence of a node to be the nodes which will be ultimately stabilized by a sustained state of this node regardless of the initial state of the system. Thus a solution to the target control problem is the set of nodes whose domain of influence can cover the desired target node states. We apply our strategy to several biological networks to demonstrate its effectiveness.