Host-Pathogen Protein Interaction Prediction Based on Local Topology Structures of a Protein Interaction Network

Abstract

Understanding how pathogen's proteins interact with its host's proteins is the key concept for understanding pathogen's infection mechanism, which can lead to the discovery of improved therapeutics for treating infectious diseases. Several studies suggest that proteins from various pathogens tend to interact with human proteins involved in the same biological pathway. This implies that pathogens are inclined to target host's proteins with similar function. In addition, conservation between a protein's function and its local topological structure in a protein-protein interaction network (PIN) has been previously characterized. This leads to the hypothesis that pathogens target the host's proteins with a similar local topological structure in a PIN. In this work, this hypothesis is examined by adding a graphlet degree vector of a protein in the human PIN as a feature in the prediction model and using that model to predict the protein-protein interaction between human and four pathogens. The results show that this graphlet degree vector increases the performance significantly for all pathogens. This suggests that the intraspecies protein-protein interactions should be taken into consideration when developing prediction methods for host-pathogen protein interaction. The results also support the hypothesis that there exists a relationship between a protein's function and the local topology of the PIN.