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As the most pervasive epigenetic mark present on mRNA and lncRNA, N6-methyladenosine (m6A) RNA methylation regulates all stages of RNA life in various biological processes and disease mechanisms. Computational methods for deciphering RNA modification have achieved great success in recent years; nevertheless, their potential remains underexploited. One reason for this is that existing models usually consider only the sequence of transcripts, ignoring the various regions (or geography) of transcripts such as 3'UTR and intron, where the epigenetic mark forms and functions. Here, we developed three simple yet powerful encoding schemes for transcripts to capture the submolecular geographic information of RNA, which is largely independent from sequences. We show that m6A prediction models based on geographic information alone can achieve comparable performances to classic sequence-based methods. Importantly, geographic information substantially enhances the accuracy of sequence-based models, enables isoform- and tissue-specific prediction of m6A sites, and improves m6A signal detection from direct RNA sequencing data. The geographic encoding schemes we developed have exhibited strong interpretability, and are applicable to not only m6A but also N1-methyladenosine (m1A), and can serve as a general and effective complement to the widely used sequence encoding schemes in deep learning applications concerning RNA transcripts., (© The Author(s) 2022. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Motivation: Increasing evidence suggests that post-transcriptional ribonucleic acid (RNA) modifications regulate essential biomolecular functions and are related to the pathogenesis of various diseases. Precise identification of RNA modification sites is essential for understanding the regulatory mechanisms of RNAs. To date, many computational approaches for predicting RNA modifications have been developed, most of which were based on strong supervision enabled by base-resolution epitranscriptome data. However, high-resolution data may not be available., Results: We propose WeakRM, the first weakly supervised learning framework for predicting RNA modifications from low-resolution epitranscriptome datasets, such as those generated from acRIP-seq and hMeRIP-seq. Evaluations on three independent datasets (corresponding to three different RNA modification types and their respective sequencing technologies) demonstrated the effectiveness of our approach in predicting RNA modifications from low-resolution data. WeakRM outperformed state-of-the-art multi-instance learning methods for genomic sequences, such as WSCNN, which was originally designed for transcription factor binding site prediction. Additionally, our approach captured motifs that are consistent with existing knowledge, and visualization of the predicted modification-containing regions unveiled the potentials of detecting RNA modifications with improved resolution., Availability Implementation: The source code for the WeakRM algorithm, along with the datasets used, are freely accessible at: https://github.com/daiyun02211/WeakRM., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author(s) 2021. Published by Oxford University Press.)

Motivation: The distribution of biological features strongly indicates their functional relevance. Compared to DNA-related features, deciphering the distribution of mRNA-related features is non-trivial due to the existence of isoform ambiguity and compositional diversity of mRNAs., Results: We propose here a rigorous statistical framework, MetaTX, for deciphering the distribution of mRNA-related features. Through a standardized mRNA model, MetaTX firstly unifies various mRNA transcripts of diverse compositions, and then corrects the isoform ambiguity by incorporating the overall distribution pattern of the features through an EM algorithm. MetaTX was tested on both simulated and real data. Results suggested that MetaTX substantially outperformed existing direct methods on simulated datasets, and that a more informative distribution pattern was produced for all the three datasets tested, which contain N6-Methyladenosine sites generated by different technologies. MetaTX should make a useful tool for studying the distribution and functions of mRNA-related biological features, especially for mRNA modifications such as N6-Methyladenosine., Availability and Implementation: The MetaTX R package is freely available at GitHub: https://github.com/yue-wang-biomath/MetaTX.1.0., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)