Proteome-wide Prediction of Signal Flow Direction in Protein Interaction Networks Based on Interacting Domains

Wei Liu, Dong Li, Jian Wang, Hongwei Xie, Yunping Zhu, Fuchu He
2009 Molecular & Cellular Proteomics  
Signal flow direction is one of the most important features of the protein-protein interactions in signaling networks. However, almost all the outcomes of current high-throughout techniques for protein-protein interactions mapping are usually supposed to be non-directional. Based on the pairwise interaction domains, here we defined a novel parameter protein interaction directional score and then used it to predict the direction of signal flow between proteins in proteome-wide signaling
more » ... Using 5-fold cross-validation, our approach obtained a satisfied performance with the accuracy 89.79%, coverage 48.08%, and error ratio 16.91%. As an application, we established an integrated human directional protein interaction network, including 2,237 proteins and 5,530 interactions, and inferred a large amount of novel signaling pathways. Directional protein interaction network was strongly supported by the known signaling pathways literature (with the 87.5% accuracy) and further analyses on the biological annotation, subcellular localization, and network topology property. Thus, this study provided an effective method to define the upstream/downstream relations of interacting protein pairs and a powerful tool to unravel the unknown signaling pathways.
doi:10.1074/mcp.m800354-mcp200 pmid:19502588 pmcid:PMC2742434 fatcat:5t2aayje4zacrhutonp56udrti