Prediction of "aggregation-prone" peptides with hybrid classification approach

Abstract

Protein aggregation is a biological phenomenon caused by misfolding proteins aggregation and is associated with a wide variety of diseases, such as Alzheimer's, Parkinson's, and prion diseases. Many studies indicate that protein aggregation is mediated by short "aggregation-prone" peptide segments. Thus, the prediction of aggregation-prone sites plays a crucial role in the research of drug targets. Compared with the labor-intensive and time-consuming experiment approaches, the computational prediction of aggregation-prone sites is much desirable due to their convenience and high efficiency. In this study, we introduce two computational approaches Aggre-Easy and Aggre-Balance for predicting aggregation residues from the sequence information; here, the protein samples are represented by the composition of k-spaced amino acid pairs (CKSAAP). And we use the hybrid classification approach to predict aggregation-prone residues, which integrates the naïve Bayes classification to reduce the number of features, and two undersampling approaches EasyEnsemble and BalanceCascade to deal with samples imbalance problem. The Aggre-Easy achieves a promising performance with a sensitivity of 79.47%, a specificity of 80.70% and a MCC of 0.42; the sensitivity, specificity, and MCC of Aggre-Balance reach 70.32%, 80.70% and 0.42. Experimental results show that the performance of Aggre-Easy and Aggre-Balance predictor is better than several other state-of-the-art predictors. A user-friendly web server is built for prediction of aggregation-prone which is freely accessible to public at the website.