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Open Access Highly Accessed Methodology article

The Use of Edge-Betweenness Clustering to Investigate Biological Function in Protein Interaction Networks

Ruth Dunn1, Frank Dudbridge2 and Christopher M Sanderson3*

Author Affiliations

1 The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK

2 MRC Biostatistics Unit, Institute of Public Health, Robinson Way, Cambridge CB2 2SR, UK

3 MRC Rosalind Franklin Centre for Genomics Research, Hinxton, Cambridge CB10 1SB, UK

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BMC Bioinformatics 2005, 6:39  doi:10.1186/1471-2105-6-39

Published: 1 March 2005



This paper describes an automated method for finding clusters of interconnected proteins in protein interaction networks and retrieving protein annotations associated with these clusters.


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.


This method provides a useful tool for rapid screening of small to medium size protein interaction datasets.