Dataset Information

DNN-m6A: A Cross-Species Method for Identifying RNA N6-Methyladenosine Sites Based on Deep Neural Network with Multi-Information Fusion.

ABSTRACT: As a prevalent existing post-transcriptional modification of RNA, N6-methyladenosine (m6A) plays a crucial role in various biological processes. To better radically reveal its regulatory mechanism and provide new insights for drug design, the accurate identification of m6A sites in genome-wide is vital. As the traditional experimental methods are time-consuming and cost-prohibitive, it is necessary to design a more efficient computational method to detect the m6A sites. In this study, we propose a novel cross-species computational method DNN-m6A based on the deep neural network (DNN) to identify m6A sites in multiple tissues of human, mouse and rat. Firstly, binary encoding (BE), tri-nucleotide composition (TNC), enhanced nucleic acid composition (ENAC), K-spaced nucleotide pair frequencies (KSNPFs), nucleotide chemical property (NCP), pseudo dinucleotide composition (PseDNC), position-specific nucleotide propensity (PSNP) and position-specific dinucleotide propensity (PSDP) are employed to extract RNA sequence features which are subsequently fused to construct the initial feature vector set. Secondly, we use elastic net to eliminate redundant features while building the optimal feature subset. Finally, the hyper-parameters of DNN are tuned with Bayesian hyper-parameter optimization based on the selected feature subset. The five-fold cross-validation test on training datasets show that the proposed DNN-m6A method outperformed the state-of-the-art method for predicting m6A sites, with an accuracy (ACC) of 73.58%-83.38% and an area under the curve (AUC) of 81.39%-91.04%. Furthermore, the independent datasets achieved an ACC of 72.95%-83.04% and an AUC of 80.79%-91.09%, which shows an excellent generalization ability of our proposed method.

SUBMITTER: Zhang L

PROVIDER: S-EPMC7997228 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:N6-methyladenosine (m6A) is the most abundant within eukaryotic messenger RNA modification, which plays an essential regulatory role in the control of cellular functions and gene expression. However, it remains an outstanding challenge to detect mRNA m6A transcriptome-wide at base resolution via experimental approaches, which are generally time-consuming and expensive. Developing computational methods is a good strategy for accurate in silico detection of m6A modification sites from the large amount of RNA sequence data. Unfortunately, the existing computational models are usually only for m6A site prediction in a single species, without considering the tissue level of species, while most of them are constructed based on low-confidence level data generated by an m6A antibody immunoprecipitation (IP)-based sequencing method, thereby restricting reliability and generalizability of proposed models. Here, we review recent advances in computational prediction of m6A sites and construct a new computational approach named im6APred using ensemble deep learning to accurately identify m6A sites based on high-confidence level data in multiple tissues of mammals. Our model im6APred builds upon a comprehensive evaluation of multiple classification methods, including four traditional classification algorithms and three deep learning methods and their ensembles. The optimal base-classifier combinations are then chosen by five-fold cross-validation test to achieve an effective stacked model. Our model im6APred can produce the area under the receiver operating characteristic curve (AUROC) in the range of 0.82-0.91 on independent tests, indicating that our model has the ability to learn general methylation rules on RNA bases and generalize to m6A transcriptome-wide identification. Moreover, AUROCs in the range of 0.77-0.96 were achieved using cross-species/tissues validation on the benchmark dataset, demonstrating differences in predictive performance at the tissue level and the need for constructing tissue-specific models for m6A site prediction.

Dataset Information

DNN-m6A: A Cross-Species Method for Identifying RNA N6-Methyladenosine Sites Based on Deep Neural Network with Multi-Information Fusion.

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