Topological estimation of signal flow in complex signaling networks

Abstract

In a cell, any information about extra- or intra-cellular changes is transferred and processed through a signaling network and dysregulation of signal flow often leads to disease such as cancer. So, understanding of signal flow in the signaling network is critical to identify drug targets. Owing to the development of high-throughput measurement technologies, the structure of a signaling network is becoming more available, but detailed kinetic parameter information about molecular interactions is still very limited. A question then arises as to whether we can estimate the signal flow based only on the structure information of a signaling network. To answer this question, we develop a novel algorithm that can estimate the signal flow using only the topological information and apply it to predict the direction of activity change in various signaling networks. Interestingly, we find that the average accuracy of the estimation algorithm is about 60–80% even though we only use the topological information. We also find that this predictive power gets collapsed if we randomly alter the network topology, showing the importance of network topology. Our study provides a basis for utilizing the topological information of signaling networks in precision medicine or drug target discovery.