Identifying Driver Nodes in the Human Signaling Network Using Structural Controllability Analysis

Cell signaling governs the basic cellular activities and coordinates the actions in cell. Abnormal regulations in cell signaling processing are responsible for many human diseases, such as diabetes and cancers. With the accumulation of massive data related to human cell signaling, it is feasible to obtain a human signaling network. Some studies have shown that interesting biological phenomenon and drug-targets could be discovered by applying structural controllability analysis to biological networks. In this work, we apply structural controllability to a human signaling network and detect driver nodes, providing a systematic analysis of the role of different proteins in controlling the human signaling network. We find that the proteins in the upstream of the signaling information flow and the low in-degree proteins play a crucial role in controlling the human signaling network. Interestingly, inputting different control signals on the regulators of the cancer-associated genes could cost less than controlling the cancer-associated genes directly in order to control the whole human signaling network in the sense that less drive nodes are needed. This research provides a fresh perspective for controlling the human cell signaling system.