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Updated: Aug 19, 2026

Genome-wide Protein-protein Interaction Screening by Protein-fragment Complementation Assay (PCA) in Living Cells
Published on: March 3, 2015
The use of edge-betweenness clustering to investigate biological function in protein interaction networks
Ruth Dunn1, Frank Dudbridge, Christopher M Sanderson
1The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK. rd3@sanger.ac.uk <rd3@sanger.ac.uk>
Background:
This paper describes an automated method for finding clusters of interconnected proteins in protein interaction networks and retrieving protein annotations associated with these clusters.
Results:
Protein interaction graphs were separated into subgraphs of interconnected proteins, using the JUNG implementation of Girvan and Newman's Edge-Betweenness algorithm. Functions were sought for these subgraphs by detecting significant correlations with the distribution of Gene Ontology terms which had been used to annotate the proteins within each cluster. The method was implemented using freely available software (JUNG and the R statistical package). Protein clusters with significant correlations to functional annotations could be identified and included groups of proteins know to cooperate in cell metabolism. The method appears to be resilient against the presence of false positive interactions.
Conclusion:
This method provides a useful tool for rapid screening of small to medium size protein interaction datasets.
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