Predicting pathway membership via domain signatures

Bioinformatics. 2008 Oct 1;24(19):2137-42. doi: 10.1093/bioinformatics/btn403. Epub 2008 Aug 1.

Abstract

Motivation: Functional characterization of genes is of great importance for the understanding of complex cellular processes. Valuable information for this purpose can be obtained from pathway databases, like KEGG. However, only a small fraction of genes is annotated with pathway information up to now. In contrast, information on contained protein domains can be obtained for a significantly higher number of genes, e.g. from the InterPro database.

Results: We present a classification model, which for a specific gene of interest can predict the mapping to a KEGG pathway, based on its domain signature. The classifier makes explicit use of the hierarchical organization of pathways in the KEGG database. Furthermore, we take into account that a specific gene can be mapped to different pathways at the same time. The classification method produces a scoring of all possible mapping positions of the gene in the KEGG hierarchy. Evaluations of our model, which is a combination of a SVM and ranking perceptron approach, show a high prediction performance. Moreover, for signaling pathways we reveal that it is even possible to forecast accurately the membership to individual pathway components.

Availability: The R package gene2pathway is a supplement to this article.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Computational Biology / methods*
  • Databases, Protein
  • Protein Structure, Tertiary*
  • Proteins / chemistry
  • Proteins / metabolism
  • Signal Transduction*

Substances

  • Proteins