A multi-layer refined network model for the identification of essential proteins

The identification of essential proteins in protein-protein interaction networks (PINs) can help to discover drug targets and prevent disease. In order to improve the accuracy of the identification of essential proteins, researchers attempted to obtain a refined PIN by combining multiple biological information to filter out some unreliable interactions in the PIN. Unfortunately, such approaches drastically reduce the number of nodes in the PIN after multiple refinements and result in a sparser PIN. It makes a considerable portion of essential proteins unidentifiable. In this paper, we propose a multi-layer refined network (MR-PIN) that addresses this problem. Firstly, four refined networks are constructed by respectively integrating different biological information into the static PIN to form a multi-layer heterogeneous network. Then scores of proteins in each network layer are calculated by the existing node ranking method, and the importance score of a protein in the MR-PIN is evaluated in terms of the geometric mean of its scores in all layers. Finally, all nodes are sorted by their importance scores to determine their essentiality. To evaluate the effectiveness of the multi-layer refined network model, we apply 16 node ranking methods on the MR-PIN, and compare the results with those on the SPIN, DPIN and RDPIN. Then the predictive performances of these ranking methods are validated in terms of the identification number of essential protein at top100 - top600, sensitivity, specificity, positive predictive value, negative predictive value, F-measure, accuracy, Jackknife, ROCAUC and PRAUC. The experimental results show that the MR-PIN is superior to the existing refined PINs in the identification accuracy of essential proteins.