Cellular signaling networks and their visualization

 

ILLES FARKAS

HUNGARIAN ACADEMY OF SCIENCES

 

Signaling pathways, e.g., TGF-beta or WNT, control a large variety of cellular processes. Before precise analyses of these pathways one should apply standardized compilation (curation) rules uniformly to all of them. However, current signaling databases do not apply such rules. We present SignaLink, a database containing 8 major signaling pathways from C. elegans, D. melanogaster, and humans. With SignaLink we found that in humans any two of the 8 pathways can cross-talk. In addition to analyzing the tissue-specificity of pathways, we identified 372 drug target candidate proteins. We predicted novel signaling pathway member proteins by comparing the signaling networks of the three organisms. SignaLink is available at http://SignaLink.org. In biomedical experiments protein functions are often altered. Unfortunately, these changes can strongly influence signaling proteins that are within a few interaction steps. This can lead to unexpected signaling changes and unwanted phenotypes. To assist experimental work (both planning and evaluation) we developed a web server, PathwayLinker. This web server links the queried proteins to signaling pathways through the interactions of the protein-protein and the genetic interaction networks. PathwayLinker is available at http://PatwhayLinker.org. In both studies we found that network modules (cellular signaling pathways) strongly overlap. We provide several interactive online visualizations of the signaling subnetworks. These visualizations are optimized for, e.g., displaying signaling pathways, viewing the ortholog networks of the three species together, or assisting the planning of experiments by listing all signaling functions in the network neighborhood of a selected protein.