Discovery of a kernel for controlling biomolecular regulatory networks

Cellular behavior is determined not by a single molecule but by many molecules that interact strongly with one another and form a complex network. It is unclear whether cellular behavior can be controlled by regulating certain molecular components in the network. By analyzing a variety of biomolecular regulatory networks, we discovered that only a small fraction of the network components need to be regulated to govern the network dynamics and control cellular behavior. We defined a minimal set of network components that must be regulated to make the cell reach a desired stable state as the control kernel and developed a general algorithm for identifying it. We found that the size of the control kernel was related to both the topological and logical characteristics of a network. Intriguingly, the control kernel of the human signaling network included many drug targets and chemical-binding interactions, suggesting therapeutic application of the control kernel.