RFEM: A framework for essential microRNA identification in mice based on rotation forest and multiple feature fusion

Abstract

With the increasing number of microRNAs (miRNAs), identifying essential miRNAs has become an important task that needs to be solved urgently. However, there are few computational methods for essential miRNA identification. Here, we proposed a novel framework called Rotation Forest for Essential MicroRNA identification (RFEM) to predict the essentiality of miRNAs in mice. We first constructed 1,264 miRNA features of all miRNA samples by fusing 38 miRNA features obtained from the PESM paper and 1,226 miRNA functional features calculated based on miRNA-target gene interactions. Then, we employed 182 training samples with 1,264 features to train the rotation forest model, which was applied to compute the essentiality scores of the candidate samples. The main innovations of RFEM were as follows: 1) miRNA functional features were introduced to enrich the diversity of miRNA features; 2) the rotation forest model used decision tree as the base classifier and could increase the difference among base classifiers through feature transformation to achieve better ensemble results. Experimental results show that RFEM significantly outperformed two previous models with the AUC (AUPR) of 0.942 (0.944) in three comparison experiments under 5-fold cross validation, which proved the model's reliable performance. Moreover, ablation study was further conducted to demonstrate the effectiveness of the novel miRNA functional features. Additionally, in the case studies of assessing the essentiality of unlabeled miRNAs, experimental literature confirmed that 7 of the top 10 predicted miRNAs have crucial biological functions in mice. Therefore, RFEM would be a reliable tool for identifying essential miRNAs.

Keywords: Ensemble method; Essentiality; MicroRNA; Principal component analysis; Rotation forest.