United Neighborhood Closeness Centrality and Orthology for Predicting Essential Proteins

Abstract

Identifying essential proteins plays an important role in disease study, drug design, and understanding the minimal requirement for cellular life. Computational methods for essential proteins discovery overcome the disadvantages of biological experimental methods that are often time-consuming, expensive, and inefficient. The topological features of protein-protein interaction (PPI) networks are often used to design computational prediction methods, such as Degree Centrality (DC), Betweenness Centrality (BC), Closeness Centrality (CC), Subgraph Centrality (SC), Eigenvector Centrality (EC), Information Centrality (IC), and Neighborhood Centrality (NC). However, the prediction accuracies of these individual methods still have space to be improved. Studies show that additional information, such as orthologous relations, helps discover essential proteins. Many researchers have proposed different methods by combining multiple information sources to gain improvement of prediction accuracy. In this study, we find that essential proteins appear in triangular structure in PPI network significantly more often than nonessential ones. Based on this phenomenon, we propose a novel pure centrality measure, so-called Neighborhood Closeness Centrality (NCC). Accordingly, we develop a new combination model, Extended Pareto Optimality Consensus model, named EPOC, to fuse NCC and Orthology information and a novel essential proteins identification method, NCCO, is fully proposed. Compared with seven existing classic centrality methods (DC, BC, IC, CC, SC, EC, and NC) and three consensus methods (PeC, ION, and CSC), our results on S.cerevisiae and E.coli datasets show that NCCO has clear advantages. As a consensus method, EPOC also yields better performance than the random walk model.