Dataset Information

LITHOPHONE: Improving lncRNA Methylation Site Prediction Using an Ensemble Predictor.

ABSTRACT: N ⁶-methyladenosine (m⁶A) is one of the most widely studied epigenetic modifications, which plays an important role in many biological processes, such as splicing, RNA localization, and degradation. Studies have shown that m⁶A on lncRNA has important functions, including regulating the expression and functions of lncRNA, regulating the synthesis of pre-mRNA, promoting the proliferation of cancer cells, and affecting cell differentiation and many others. Although a number of methods have been proposed to predict m⁶A RNA methylation sites, most of these methods aimed at general m⁶A sites prediction without noticing the uniqueness of the lncRNA methylation prediction problem. Since many lncRNAs do not have a polyA tail and cannot be captured in the polyA selection step of the most widely adopted RNA-seq library preparation protocol, lncRNA methylation sites cannot be effectively captured and are thus likely to be significantly underrepresented in existing experimental data affecting the accuracy of existing predictors. In this paper, we propose a new computational framework, LITHOPHONE, which stands for long noncoding RNA methylation sites prediction from sequence characteristics and genomic information with an ensemble predictor. We show that the methylation sites of lncRNA and mRNA have different patterns exhibited in the extracted features and should be differently handled when making predictions. Due to the used experiment protocols, the number of known lncRNA m⁶A sites is limited, and insufficient to train a reliable predictor; thus, the performance can be improved by combining both lncRNA and mRNA data using an ensemble predictor. We show that the newly developed LITHOPHONE approach achieved a reasonably good performance when tested on independent datasets (AUC: 0.966 and 0.835 under full transcript and mature mRNA modes, respectively), marking a substantial improvement compared with existing methods. Additionally, LITHOPHONE was applied to scan the entire human lncRNAome for all possible lncRNA m⁶A sites, and the results are freely accessible at: http://180.208.58.19/lith/.

SUBMITTER: Liu L

PROVIDER: S-EPMC7297269 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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LITHOPHONE: Improving lncRNA Methylation Site Prediction Using an Ensemble Predictor.

Liu Lian L Lei Xiujuan X Fang Zengqiang Z Tang Yujiao Y Meng Jia J Wei Zhen Z

Frontiers in genetics 20200609

N 6-methyladenosine (m6A) is one of the most widely studied epigenetic modifications, which plays an important role in many biological processes, such as splicing, RNA localization, and degradation. Studies have shown that m6A on lncRNA has important functions, including regulating the expression and functions of lncRNA, regulating the synthesis of pre-mRNA, promoting the proliferation of cancer cells, and affecting cell differentiation and many others. Al ...[more]

PMID: 32582286

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Project description:BackgroundRecent research recommends that epi-transcriptome regulation through post-transcriptional RNA modifications is essential for all sorts of RNA. Exact identification of RNA modification is vital for understanding their purposes and regulatory mechanisms. However, traditional experimental methods of identifying RNA modification sites are relatively complicated, time-consuming, and laborious. Machine learning approaches have been applied in the procedures of RNA sequence features extraction and classification in a computational way, which may supplement experimental approaches more efficiently. Recently, convolutional neural network (CNN) and long short-term memory (LSTM) have been demonstrated achievements in modification site prediction on account of their powerful functions in representation learning. However, CNN can learn the local response from the spatial data but cannot learn sequential correlations. And LSTM is specialized for sequential modeling and can access both the contextual representation but lacks spatial data extraction compared with CNN. There is strong motivation to construct a prediction framework using natural language processing (NLP), deep learning (DL) for these reasons.ResultsThis study presents an ensemble multiscale deep learning predictor (EMDLP) to identify RNA methylation sites in an NLP and DL way. It organically combines the dilated convolution and Bidirectional LSTM (BiLSTM), which helps to take better advantage of the local and global information for site prediction. The first step of EMDLP is to represent the RNA sequences in an NLP way. Thus, three encodings, e.g., RNA word embedding, One-hot encoding, and RGloVe, which is an improved learning method of word vector representation based on GloVe, are adopted to decipher sites from the viewpoints of the local and global information. Then, a dilated convolutional Bidirectional LSTM network (DCB) model is constructed with the dilated convolutional neural network (DCNN) followed by BiLSTM to extract potential contributing features for methylation site prediction. Finally, these three encoding methods are integrated by a soft vote to obtain better predictive performance. Experiment results on m1A and m6A reveal that the area under the receiver operating characteristic(AUROC) of EMDLP obtains respectively 95.56%, 85.24%, and outperforms the state-of-the-art models. To maximize user convenience, a user-friendly webserver for EMDLP was publicly available at http://www.labiip.net/EMDLP/index.php ( http://47.104.130.81/EMDLP/index.php ).ConclusionsWe developed a predictor for m1A and m6A methylation sites.

Project description:Brain age is an imaging-based biomarker with excellent feasibility for characterizing individual brain health and may serve as a single quantitative index for clinical and domain-specific usage. Brain age has been successfully estimated using extensive neuroimaging data from healthy participants with various feature extraction and conventional machine learning (ML) approaches. Recently, several end-to-end deep learning (DL) analytical frameworks have been proposed as alternative approaches to predict individual brain age with higher accuracy. However, the optimal approach to select and assemble appropriate input feature sets for DL analytical frameworks remains to be determined. In the Predictive Analytics Competition 2019, we proposed a hierarchical analytical framework which first used ML algorithms to investigate the potential contribution of different input features for predicting individual brain age. The obtained information then served as a priori knowledge for determining the input feature sets of the final ensemble DL prediction model. Systematic evaluation revealed that ML approaches with multiple concurrent input features, including tissue volume and density, achieved higher prediction accuracy when compared with approaches with a single input feature set [Ridge regression: mean absolute error (MAE) = 4.51 years, R 2 = 0.88; support vector regression, MAE = 4.42 years, R 2 = 0.88]. Based on this evaluation, a final ensemble DL brain age prediction model integrating multiple feature sets was constructed with reasonable computation capacity and achieved higher prediction accuracy when compared with ML approaches in the training dataset (MAE = 3.77 years; R 2 = 0.90). Furthermore, the proposed ensemble DL brain age prediction model also demonstrated sufficient generalizability in the testing dataset (MAE = 3.33 years). In summary, this study provides initial evidence of how-to efficiency for integrating ML and advanced DL approaches into a unified analytical framework for predicting individual brain age with higher accuracy. With the increase in large open multiple-modality neuroimaging datasets, ensemble DL strategies with appropriate input feature sets serve as a candidate approach for predicting individual brain age in the future.

Project description:BACKGROUND:In plants, long non-protein coding RNAs are believed to have essential roles in development and stress responses. However, relative to advances on discerning biological roles for long non-protein coding RNAs in animal systems, this RNA class in plants is largely understudied. With comparatively few validated plant long non-coding RNAs, research on this potentially critical class of RNA is hindered by a lack of appropriate prediction tools and databases. Supervised learning models trained on data sets of mostly non-validated, non-coding transcripts have been previously used to identify this enigmatic RNA class with applications largely focused on animal systems. Our approach uses a training set comprised only of empirically validated long non-protein coding RNAs from plant, animal, and viral sources to predict and rank candidate long non-protein coding gene products for future functional validation. RESULTS:Individual stochastic gradient boosting and random forest classifiers trained on only empirically validated long non-protein coding RNAs were constructed. In order to use the strengths of multiple classifiers, we combined multiple models into a single stacking meta-learner. This ensemble approach benefits from the diversity of several learners to effectively identify putative plant long non-coding RNAs from transcript sequence features. When the predicted genes identified by the ensemble classifier were compared to those listed in GreeNC, an established plant long non-coding RNA database, overlap for predicted genes from Arabidopsis thaliana, Oryza sativa and Eutrema salsugineum ranged from 51 to 83% with the highest agreement in Eutrema salsugineum. Most of the highest ranking predictions from Arabidopsis thaliana were annotated as potential natural antisense genes, pseudogenes, transposable elements, or simply computationally predicted hypothetical protein. Due to the nature of this tool, the model can be updated as new long non-protein coding transcripts are identified and functionally verified. CONCLUSIONS:This ensemble classifier is an accurate tool that can be used to rank long non-protein coding RNA predictions for use in conjunction with gene expression studies. Selection of plant transcripts with a high potential for regulatory roles as long non-protein coding RNAs will advance research in the elucidation of long non-protein coding RNA function.

Dataset Information

LITHOPHONE: Improving lncRNA Methylation Site Prediction Using an Ensemble Predictor.

Publications

LITHOPHONE: Improving lncRNA Methylation Site Prediction Using an Ensemble Predictor.

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