Signalling networks in eukaryotes are made up of upstream and downstream subnetworks.
The upstream subnetwork contains the intertwined network of signaling pathways, while the downstream regulatory part contains transcription factors and their binding sites on the DNA as well as microRNAs and their mRNA targets. Currently, most signalling and regulatory databases contain only a subsection of this network, making comprehensive analyses highly time-consuming and dependent on specific data handling expertise. The need for detailed mapping of signalling systems is also supported by the fact that several drug development failures were caused by undiscovered cross-talk or regulatory effects of drug targets.
SignaLink’s novel, multi-layered (onion-like) database structure is made up of signalling pathways, their pathway regulators (e.g., scaffold and endocytotic proteins) and modifier enzymes (e.g. phosphatases, ubiquitin ligases), as well as transcriptional and post-transcriptional regulators of all of these components. The user-friendly website allows the interactive exploration of how each signalling protein is regulated. The customisable download page enables the analysis of any user-specified part of the signaling network. Compared to other signalling resources, distinctive features of SignaLink are the following:
- It involves experimental data not only from humans but from two invertebrate model organisms, C. elegans and D. melanogaster
- Combines manual curation with large-scale datasets
- Provides confidence scores for each interaction
- Operates a customisable download page with multiple file formats (CSV, SBML, BioPAX, Cytoscape, SQL
- With SignaLink as a single resource, users can effectively analyse signalling pathways, scaffold proteins, modifier enzymes, transcription factors and miRNAs that are important in the regulation of signalling processes