YaleGerstein Lab

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

Haiyuan Yu*, Philip Kim*, Emmett Sprecher, Valery Trifonov, and Mark 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, 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.

Supplementary Data Files
1. Interaction network
2. Regulatory network
3. Metabolic network
4. Genetic network
5. Phosphorylation network
6. FYI network
7. DIP-core network
8. Expression data
9. MIPS complex data
Supplementary Result Files
1. Betweenness in Interaction network
2. Betweenness in Regulatory network
3. Betweenness in Metabolic network
4. Betweenness in Genetic network
5. Betweenness in Phosphorylation network
6. Betweenness in FYI network
7. Betweenness in DIP-core network
Please note that the network files and the corresponding result files will be updated regularly as the networks grow in size.
Scripts and binaries
       C scripts
 1. Prepare input datasets
 2. Calculating betweenness
 3. All C scripts
 1. Prepare input datasets
 2. Calculating betweenness
 Please note that you first have to convert your input file into a binary file using "convert2mtx" before you can run "betweeenness". In other words, "betweenness" only takes the output from "convert2mtx" as input!!! Running any script without any argument will prompt you the information about how to use it.

*These two authors contribute equally to this work

Last modified on July 5th, 2007