EnANNDeep: An Ensemble-based lncRNA-protein Interaction Prediction Framework with Adaptive k-Nearest Neighbor Classifier and Deep Models.

Abstract

lncRNA-protein interactions (LPIs) prediction can deepen the understanding of many important biological processes. Artificial intelligence methods have reported many possible LPIs. However, most computational techniques were evaluated mainly on one dataset, which may produce prediction bias. More importantly, they were validated only under cross validation on lncRNA-protein pairs, and did not consider the performance under cross validations on lncRNAs and proteins, thus fail to search related proteins/lncRNAs for a new lncRNA/protein. Under an ensemble learning framework (EnANNDeep) composed of adaptive k-nearest neighbor classifier and Deep models, this study focuses on systematically finding underlying linkages between lncRNAs and proteins. First, five LPI-related datasets are arranged. Second, multiple source features are integrated to depict an lncRNA-protein pair. Third, adaptive k-nearest neighbor classifier, deep neural network, and deep forest are designed to score unknown lncRNA-protein pairs, respectively. Finally, interaction probabilities from the three predictors are integrated based on a soft voting technique. In comparing to five classical LPI identification models (SFPEL, PMDKN, CatBoost, PLIPCOM, and LPI-SKF) under fivefold cross validations on lncRNAs, proteins, and LPIs, EnANNDeep computes the best average AUCs of 0.8660, 0.8775, and 0.9166, respectively, and the best average AUPRs of 0.8545, 0.8595, and 0.9054, respectively, indicating its superior LPI prediction ability. Case study analyses indicate that SNHG10 may have dense linkage with Q15717. In the ensemble framework, adaptive k-nearest neighbor classifier can separately pick the most appropriate k for each query lncRNA-protein pair. More importantly, deep models including deep neural network and deep forest can effectively learn the representative features of lncRNAs and proteins.