Function Analysis of Human Protein Interactions Based on a Novel Minimal Loop Algorithm

Background: Various properties of Protein-Protein Interaction (PPI) network have been widely exploited to discover the topological organizing principle and the crucial function motifs involving specific biological pathway or disease process. The current motifs of PPI network are either detected by the topology-based coarse grain algorithms, i.e. community discovering, or depended on the limited-accessible protein annotation data derived precise algorithms. However, the identified network motifs are hardly compatible with the well-defined biological functions according to those two types of methods. Method: In this paper, we proposed a minimal protein loop finding method to explore the elementary structural motifs of human PPI network. Initially, an improved article exchange model was designed to search all the independent shortest protein loops of PPI network. Furthermore, Gene Ontology (GO) based function clustering analysis was implemented to identify the biological functions of the shortest protein loops. Additionally, the disease process associated shortest protein loops were considered as the potential drug targets. Result: Our proposed method presents the lowest computational complexity and the highest functional consistency, compared to the three other methods. The functional enrichment and clustering analysis for the identified minimal protein loops revealed the high correlation between the protein loops and the corresponding biological functions, particularly, statistical analysis presenting the protein loops with the length less than 4 is closely connected with some disease process, suggesting the potential drug target. Conclusion: Our minimal protein loop method provides a novel manner to precisely define the functional motif of PPI network, which extends the current knowledge about the cooperating mechanisms and topological properties of protein modules composed of the short loops.