Apr 24, 2007

The importance of bottlenecks in protein networks: correlation with gene essentiality and expression dynamics

PLoS Computational Biology
Haiyuan YuMark B Gerstein

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, 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.

Mentioned in this Paper

In Silico
Cyclin-dependent kinase-activating kinase
Biochemical Pathway
Proteasome Pathway
Sporulation
Genome
Enzymes, antithrombotic
Metabolic Networks
Complex (molecular entity)
Protein Phosphorylation

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