The Importance of Bottlenecks in Protein Networks: Correlation with Gene Essentiality and Expression Dynamics

Abstract: It has been a long-standing goal in systems biology to find relations between the topological properties and functional features of protein networks. However, most of the focus in network studies has been on highly connected proteins ("hubs"). As a complementary notion, we define bottlenecks as proteins with a high betweenness centrality, i.e., network nodes that have a high number of shortest paths going through them. We found that bottlenecks are key connector proteins with surprising functional and dynamic properties. In particular, bottlenecks are more likely to be essential proteins. In fact, in regulatory and other networks with directed edges, betweenness (i.e., "bottleneck-ness") is a much more significant indicator of essentiality than degree (i.e., "hub-ness"). Furthermore, bottlenecks correspond to the dynamic components of the interaction network - they are significantly less well co-expressed with their neighbors than non-bottlenecks, implying that expression dynamics is wired into the network topology.