MOTIVATION: Clustering of protein-protein interaction networks is one of the most common approaches for predicting functional modules, protein complexes and protein functions. But, how well does clustering perform at these tasks? RESULTS: We develop a general framework to assess how well computationally-derived clusters in physical interactomes overlap functional modules derived via the Gene Ontology (GO). Using this framework, we evaluate six diverse network clustering algorithms using S. cerevisiae and show that (1) the performances of these algorithms can differ substantially when run on the same network and (2) their relative performances change depending upon the topological characteristics of the network under consideration. For the specific task of function prediction in S. cerevisiae, we demonstrate that, surprisingly, a simple non-clustering guilt-by-association approach outperforms widely-used clustering based approaches that annotate a protein with the over-represented biological process and cellular component terms in its cluster; this is true over the range of clustering algorithms considered. Further analysis parameterizes performance based on the number of annotated proteins, and suggests when clustering approaches should be used for interactome functional analyses. Overall our results suggest a re-examination of when and how clustering approaches should be applied to physical interactomes, and establishes guidelines by which novel clustering approaches for biological networks should be justified and evaluated with respect to functional analysis. CONTACT: email@example.com SUPPLEMENTARY INFORMATION: Supplementary data available at Bioinformatics online.
|Evidence ID||Analyze ID||Interactor||Interactor Systematic Name||Interactor||Interactor Systematic Name||Type||Assay||Annotation||Action||Modification||Phenotype||Source||Reference||Note|
|Evidence ID||Analyze ID||Gene||Gene Systematic Name||Gene Ontology Term||Gene Ontology Term ID||Qualifier||Aspect||Method||Evidence||Source||Assigned On||Annotation Extension||Reference|
|Evidence ID||Analyze ID||Gene||Gene Systematic Name||Phenotype||Experiment Type||Experiment Type Category||Mutant Information||Strain Background||Chemical||Details||Reference|
|Evidence ID||Analyze ID||Regulator||Regulator Systematic Name||Target||Target Systematic Name||Experiment||Assay||Construct||Conditions||Strain Background||Reference|