StackRAM: a cross-species method for identifying RNA N6-methyladenosine sites based on stacked ensemble

Abstract

N6-methyladenosine is a prevalent RNA methylation modification, which plays an important role in various biological processes. Accurate identification of the m6A sites is fundamental to deeply understand the biological functions and mechanisms of the modification. However, the experimental methods for detecting m6A sites are usually time-consuming and expensive, and various computational methods have been developed to identify m6A sites in RNA. This paper proposes a novel cross-species computational method StackRAM using machine learning algorithms to identify the m6A sites in S. cerevisiaeH. sapiens and A. thaliana. First, the RNA sequences features are extracted through binary encoding, chemical property, nucleotide frequency, k-mer nucleotide frequency, pseudo dinucleotide composition, and position-specific trinucleotide propensity, and the initial feature set is obtained by feature fusion. Secondly, the Elastic Net is used for the first time to filter redundant and noisy information and retain important features for m6A sites classification. Finally, the base-classifiers output probabilities are combined with the optimal feature subset corresponding to the Elastic Net, and the combination feature input the second-stage meta-classifier SVM. The jackknife test on training dataset S. cerevisiae indicates that the prediction performance of StackRAM is superior to the current state-of-the-art methods. StackRAM prediction accuracy for independent test datasets H. sapiens and A. thaliana reach 92.30% and 87.06%, respectively. Therefore, StackRAM has development potential in cross-species prediction and can be a useful method for identifying m6A sites. The source code and all datasets are available at https://github.com/QUST-AIBBDRC/StackRAM/.