Integrating domain similarity to improve protein complexes identification in TAP-MS data

Detecting protein complexes in protein-protein interaction (PPI) networks plays an important role in improving our understanding of the dynamic of cellular organisation. However, protein interaction data generated by high-throughput experiments such as yeast-two-hybrid (Y2H) and tandem affinity-purification/mass-spectrometry (TAP-MS) are characterised by the presence of a significant number of false positives and false negatives. In recent years there has been a growing trend to incorporate diverse domain knowledge to support large-scale analysis of PPI networks.

This paper presents a new algorithm, by incorporating Gene Ontology (GO) based semantic similarities, to detect protein complexes from PPI networks generated by TAP-MS. By taking co-complex relations in TAP-MS data into account, TAP-MS PPI networks are modelled as bipartite graph, where bait proteins consist of one set of nodes and prey proteins are on the other. Similarities between pairs of bait proteins are computed by considering both the topological features and GO-driven semantic similarities. Bait proteins are then grouped in to sets of clusters based on their pair-wise similarities to produce a set of 'seed' clusters. An expansion process is applied to each 'seed' cluster to recruit prey proteins which are significantly associated with the same set of bait proteins. Thus, completely identified protein complexes are then obtained.

The proposed algorithm has been applied to real TAP-MS PPI networks. Fifteen quality measures have been employed to evaluate the quality of generated protein complexes. Experimental results show that the proposed algorithm has greatly improved the accuracy of identifying complexes and outperformed several state-of-the-art clustering algorithms. Moreover, by incorporating semantic similarity, the proposed algorithm is more robust to noises in the networks.