Uniformly curated signaling pathways reveal tissue-specific cross-talks and support drug target discovery

Bioinformatics. 2010 Aug 15;26(16):2042-50. doi: 10.1093/bioinformatics/btq310. Epub 2010 Jun 11.

Abstract

Motivation: Signaling pathways control a large variety of cellular processes. However, currently, even within the same database signaling pathways are often curated at different levels of detail. This makes comparative and cross-talk analyses difficult.

Results: We present SignaLink, a database containing eight major signaling pathways from Caenorhabditis elegans, Drosophila melanogaster and humans. Based on 170 review and approximately 800 research articles, we have compiled pathways with semi-automatic searches and uniform, well-documented curation rules. We found that in humans any two of the eight pathways can cross-talk. We quantified the possible tissue- and cancer-specific activity of cross-talks and found pathway-specific expression profiles. In addition, we identified 327 proteins relevant for drug target discovery.

Conclusions: We provide a novel resource for comparative and cross-talk analyses of signaling pathways. The identified multi-pathway and tissue-specific cross-talks contribute to the understanding of the signaling complexity in health and disease, and underscore its importance in network-based drug target selection.

Availability: http://SignaLink.org.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caenorhabditis elegans / metabolism
  • Databases, Protein*
  • Drosophila melanogaster / metabolism
  • Drug Discovery
  • Humans
  • Intracellular Signaling Peptides and Proteins / antagonists & inhibitors
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Neoplasms / metabolism
  • Signal Transduction* / drug effects

Substances

  • Intracellular Signaling Peptides and Proteins