Uncovering packaging features of co-regulated modules based on human protein interaction and transcriptional regulatory networks

BMC Bioinformatics. 2010 Jul 22:11:392. doi: 10.1186/1471-2105-11-392.

Abstract

Background: Network co-regulated modules are believed to have the functionality of packaging multiple biological entities, and can thus be assumed to coordinate many biological functions in their network neighbouring regions.

Results: Here, we weighted edges of a human protein interaction network and a transcriptional regulatory network to construct an integrated network, and introduce a probabilistic model and a bipartite graph framework to exploit human co-regulated modules and uncover their specific features in packaging different biological entities (genes, protein complexes or metabolic pathways). Finally, we identified 96 human co-regulated modules based on this method, and evaluate its effectiveness by comparing it with four other methods.

Conclusions: Dysfunctions in co-regulated interactions often occur in the development of cancer. Therefore, we focussed on an example co-regulated module and found that it could integrate a number of cancer-related genes. This was extended to causal dysfunctions of some complexes maintained by several physically interacting proteins, thus coordinating several metabolic pathways that directly underlie cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Databases, Genetic
  • Gene Regulatory Networks*
  • Humans
  • Metabolic Networks and Pathways
  • Models, Genetic*
  • Models, Statistical*
  • Neoplasms / genetics
  • Proteins / metabolism*

Substances

  • Proteins