Functional diversity of topological modules in human protein-protein interaction networks

A large-scale molecular interaction network of protein-protein interactions (PPIs) enables the automatic detection of molecular functional modules through a computational approach. However, the functional modules that are typically detected by topological community detection algorithms may be diverse in functional homogeneity and are empirically considered to be default functional modules. Thus, a significant challenge that has been described but not elucidated is investigating the relationship between topological modules and functional modules. We systematically investigated this issue by initially using seven widely used community detection algorithms to partition the PPI network into communities. Four homogeneity measures were subsequently implemented to evaluate the functional homogeneity of protein community. We determined that a significant portion of topological modules with heterogeneous functionality exists and should be further investigated; moreover, these findings indicated that topologically based functional module detection approaches must be reconsidered. Furthermore, we found that the functional homogeneity of topological modules is positively correlated with their edge densities, degree of association with diseases and general Gene Ontology (GO) terms. Thus, topologically based module detection approaches should be used with caution in the identification of functional modules with high homogeneity.