YaleGerstein Lab

Design principles of molecular networks revealed by global comparisons and composite motifs

Haiyuan Yu*, Yu Xia*, Valery Trifonov, and Mark Gerstein

Background: Molecular networks are of great current interest, particularly with the publication of many large-scale data sets in yeast. Previous analyses have focused on the topological structure of individual networks.

Results: Here, we present a global comparison of the four basic molecular networks: regulatory, co-expression, interaction, and metabolic.

Conclusions: We find that in terms of overall topological correlation -- whether nearby proteins in one network tend to be close in another -- all four networks are quite similar. However, focusing on the occurrence of more local features, we first introduce the concept of composite hubs ĘC hubs shared by more than one network. We find that the four networks can be divided into two different classes: regulation and action. The later group -- comprising metabolic, co-expression, and interaction networks -- share the same scaffolding of central hubs, whereas the regulatory network uses distinctly different regulator hubs. Finally, we examine the inter-relationship between the regulatory network and each of the three action networks, focusing on 3 basic composite motifs -- triangles, trusses, and bridges -- that involve different levels of regulation of a pair of separated genes. The analysis of these shows that action networks further divide into two groups. On the one hand, interaction and co-expression networks tend to have short-range relationships, with directly interacting and co-expressed proteins sharing common regulators. On the other, the metabolic network contains many long-distance relationships: far-away enzymes in the same pathway often have time-delayed expression relationships that are well-coordinated by bridging connections between their regulators.

Supplementary Data
 1. Yeast interaction network: Each row contains a pair of interacting proteins
 2. Yeast co-expression network: Each row contains a pair of co-expressed proteins
 3. Yeast metabolic network: Each row contains a pair of adjacent enzymes
 4. Yeast regulatory network: Each row contains a TF-target pair. The first one is the TF, the second one is the target gene of this TF

*These two authors contribute equally to this work

Last modified on May 12th, 2006