The importance of bottlenecks in protein networks: correlation with gene essentiality and expression dynamics.
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, it is possible to define bottlenecks as proteins with a high betweenness centrality (i.e., network nodes that have many "shortest paths" going through them, analogous to major bridges and tunnels on a highway map). Bottlenecks are, in fact, key connector proteins with surprising functional and dynamic properties. In particular, they are more likely to be essential proteins. In fact, in regulatory and other directed networks, 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 coexpressed with their neighbors than non-bottlenecks, implying that expression dynamics is wired into the network topology.
Yu
Haiyuan
H
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut, United States of America.
Kim
Philip M
PM
Sprecher
Emmett
E
Trifonov
Valery
V
Gerstein
Mark
M
D000465:Algorithms; D003198:Computer Simulation; D015870:Gene Expression / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D008954:Models, Biological; D020543:Proteome / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013223:Statistics as Topic; D014157:Transcription Factors / Q000378:metabolism*
D020543:Proteome; D014157:Transcription Factors