Gene network interconnectedness and the generalized topological overlap measure

BMC Bioinformatics. 2007 Jan 24;8:22. doi: 10.1186/1471-2105-8-22.

Abstract

Background: Network methods are increasingly used to represent the interactions of genes and/or proteins. Genes or proteins that are directly linked may have a similar biological function or may be part of the same biological pathway. Since the information on the connection (adjacency) between 2 nodes may be noisy or incomplete, it can be desirable to consider alternative measures of pairwise interconnectedness. Here we study a class of measures that are proportional to the number of neighbors that a pair of nodes share in common. For example, the topological overlap measure by Ravasz et al. 1 can be interpreted as a measure of agreement between the m = 1 step neighborhoods of 2 nodes. Several studies have shown that two proteins having a higher topological overlap are more likely to belong to the same functional class than proteins having a lower topological overlap. Here we address the question whether a measure of topological overlap based on higher-order neighborhoods could give rise to a more robust and sensitive measure of interconnectedness.

Results: We generalize the topological overlap measure from m = 1 step neighborhoods to m > or = 2 step neighborhoods. This allows us to define the m-th order generalized topological overlap measure (GTOM) by (i) counting the number of m-step neighbors that a pair of nodes share and (ii) normalizing it to take a value between 0 and 1. Using theoretical arguments, a yeast co-expression network application, and a fly protein network application, we illustrate the usefulness of the proposed measure for module detection and gene neighborhood analysis.

Conclusion: Topological overlap can serve as an important filter to counter the effects of spurious or missing connections between network nodes. The m-th order topological overlap measure allows one to trade-off sensitivity versus specificity when it comes to defining pairwise interconnectedness and network modules.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Algorithms
  • Animals
  • Cluster Analysis
  • Computational Biology / methods*
  • Drosophila melanogaster
  • Fungal Proteins / metabolism
  • Gene Regulatory Networks*
  • Models, Genetic
  • Models, Statistical
  • Models, Theoretical
  • Protein Interaction Mapping

Substances

  • Fungal Proteins