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Proteome-wide prediction of signal flow direction in protein interaction networks based on interacting domains.


ABSTRACT: 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 networks. 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.

SUBMITTER: Liu W 

PROVIDER: S-EPMC2742434 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature

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Proteome-wide prediction of signal flow direction in protein interaction networks based on interacting domains.

Liu Wei W   Li Dong D   Wang Jian J   Xie Hongwei H   Zhu Yunping Y   He Fuchu F  

Molecular & cellular proteomics : MCP 20090605 9


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 networks.  ...[more]

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