Dataset Information

Identifying RNA N6-Methyladenine Sites in Three Species Based on a Markov Model.

ABSTRACT: N6-methyladenosine (m6A), the most common posttranscriptional modification in eukaryotic mRNAs, plays an important role in mRNA splicing, editing, stability, degradation, etc. Since the methylation state is dynamic, methylation sequencing needs to be carried out over different time periods, which brings some difficulties to identify the RNA methyladenine sites. Thus, it is necessary to develop a fast and accurate method to identify the RNA N6-methyladenosine sites in the transcriptome. In this study, we use first-order and second-order Markov models to identify RNA N6-methyladenine sites in three species (Saccharomyces cerevisiae, mouse, and Homo sapiens). These two methods can fully consider the correlation between adjacent nucleotides. The results show that the performance of our method is better than that of other existing methods. Furthermore, the codons encoded by three nucleotides have biases in mRNA, and a second-order Markov model can capture this kind of information exactly. This may be the main reason why the performance of the second-order Markov model is better than that of the first-order Markov model in the m6A prediction problem. In addition, we provide a corresponding web tool called MM-m6APred.

SUBMITTER: Pian C

PROVIDER: S-EPMC8017269 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

Identifying RNA N6-Methyladenine Sites in Three Species Based on a Markov Model.

Pian Cong C Yang Zhixin Z Yang Yuqian Y Zhang Liangyun L Chen Yuanyuan Y

Frontiers in genetics 20210319

N6-methyladenosine (m6A), the most common posttranscriptional modification in eukaryotic mRNAs, plays an important role in mRNA splicing, editing, stability, degradation, etc. Since the methylation state is dynamic, methylation sequencing needs to be carried out over different time periods, which brings some difficulties to identify the RNA methyladenine sites. Thus, it is necessary to develop a fast and accurate method to identify the RNA N6-methyladenosine sites in the transcriptome. In this s ...[more]

PMID: 33815484

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Project description:DNA N6-Methyladenine (6mA) is a common epigenetic modification, which plays some significant roles in the growth and development of plants. It is crucial to identify 6mA sites for elucidating the functions of 6mA. In this article, a novel model named i6mA-vote is developed to predict 6mA sites of plants. Firstly, DNA sequences were coded into six feature vectors with diverse strategies based on density, physicochemical properties, and position of nucleotides, respectively. To find the best coding strategy, the feature vectors were compared on several machine learning classifiers. The results suggested that the position of nucleotides has a significant positive effect on 6mA sites identification. Thus, the dinucleotide one-hot strategy which can describe position characteristics of nucleotides well was employed to extract DNA features in our method. Secondly, DNA sequences of Rosaceae were divided into a training dataset and a test dataset randomly. Finally, i6mA-vote was constructed by combining five different base-classifiers under a majority voting strategy and trained on the Rosaceae training dataset. The i6mA-vote was evaluated on the task of predicting 6mA sites from the genome of the Rosaceae, Rice, and Arabidopsis separately. In Rosaceae, the performances of i6mA-vote were 0.955 on accuracy (ACC), 0.909 on Matthew correlation coefficients (MCC), 0.955 on sensitivity (SN), and 0.954 on specificity (SP). Those indicators, in the order of ACC, MCC, SN, SP, were 0.882, 0.774, 0.961, and 0.803 on Rice while they were 0.798, 0.617, 0.666, and 0.929 on Arabidopsis. According to the indicators, our method was effectiveness and better than other concerned methods. The results also illustrated that i6mA-vote does not only well in 6mA sites prediction of intraspecies but also interspecies plants. Moreover, it can be seen that the specificity is distinctly lower than the sensitivity in Rice while it is just the opposite in Arabidopsis. It may be resulted from sequence similarity among Rosaceae, Rice and Arabidopsis.

Project description:RNA N$^{6}$-methyladenosine (m$^{6}$A) is a critical epigenetic modification closely related to rice growth, development, and stress response. m$^{6}$A accurate identification, directly related to precision rice breeding and improvement, is fundamental to revealing phenotype regulatory and molecular mechanisms. Faced on rice m$^{6}$A variable-length sequence, to input into the model, the maximum length padding and label encoding usually adapt to obtain the max-length padded sequence for prediction. Although this can retain complete sequence information, resulting in sparse information and invalid padding, reducing feature extraction accuracy. Simultaneously, existing rice-specific m$^{6}$A prediction methods are still at an early stage. To address these issues, we develop a new end-to-end deep learning framework, MFDm$^{6}$ARice, for predicting rice m$^{6}$A sites. In particular, to alleviate sparseness, we construct a multi-kernel feature fusion module to mine essential information in max-length padded sequences by multi-kernel feature extraction function and effectively transfer information through global-local dynamic fusion function. Concurrently, considering the complexity and computational efficiency of high-dimensional features caused by invalid padding, we design a downsampling residual feature embedding module to optimize feature space compression and achieve accurate feature expression and efficient computational performance. Experiments show that MFDm$^{6}$ARice outperforms comparison methods in cross-validation, same- and cross-species independent test sets, demonstrating good robustness and generalization. The application on maize m$^{6}$A indicates the MFDm$^{6}$ARice's scalability. Further investigations have shown that combining different kernel features, focusing on global channel-local spatial, and employing reasonable downsampling and residual connections can improve feature representation and extraction, ensure effective information transfer, and significantly enhance model performance.

Dataset Information

Identifying RNA N6-Methyladenine Sites in Three Species Based on a Markov Model.

Publications

Identifying RNA N6-Methyladenine Sites in Three Species Based on a Markov Model.

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