Multi-task adaptive pooling enabled synergetic learning of RNA modification across tissue, type and species from low-resolution epitranscriptomes.

Post- and co-transcriptional RNA modifications are found to play various roles in regulating essential biological processes at all stages of RNA life. Precise identification of RNA modification sites is thus crucial for understanding the related molecular functions and specific regulatory circuitry. To date, a number of computational approaches have been developed for in silico identification of RNA modification sites; however, most of them require learning from base-resolution epitranscriptome datasets, which are generally scarce and available only for a limited number of experimental conditions, and predict only a single modification, even though there are multiple inter-related RNA modification types available. In this study, we proposed AdaptRM, a multi-task computational method for synergetic learning of multi-tissue, type and species RNA modifications from both high- and low-resolution epitranscriptome datasets. By taking advantage of adaptive pooling and multi-task learning, the newly proposed AdaptRM approach outperformed the state-of-the-art computational models (WeakRM and TS-m6A-DL) and two other deep-learning architectures based on Transformer and ConvMixer in three different case studies for both high-resolution and low-resolution prediction tasks, demonstrating its effectiveness and generalization ability. In addition, by interpreting the learned models, we unveiled for the first time the potential association between different tissues in terms of epitranscriptome sequence patterns. AdaptRM is available as a user-friendly web server from http://www.rnamd.org/AdaptRM together with all the codes and data used in this project.

Attention-based multi-label neural networks for integrated prediction and interpretation of twelve widely occurring RNA modifications.

Recent studies suggest that epi-transcriptome regulation via post-transcriptional RNA modifications is vital for all RNA types. Precise identification of RNA modification sites is essential for understanding the functions and regulatory mechanisms of RNAs. Here, we present MultiRM, a method for the integrated prediction and interpretation of post-transcriptional RNA modifications from RNA sequences. Built upon an attention-based multi-label deep learning framework, MultiRM not only simultaneously predicts the putative sites of twelve widely occurring transcriptome modifications (m6A, m1A, m5C, m5U, m6Am, m7G, Ψ, I, Am, Cm, Gm, and Um), but also returns the key sequence contents that contribute most to the positive predictions. Importantly, our model revealed a strong association among different types of RNA modifications from the perspective of their associated sequence contexts. Our work provides a solution for detecting multiple RNA modifications, enabling an integrated analysis of these RNA modifications, and gaining a better understanding of sequence-based RNA modification mechanisms.

Predict Epitranscriptome Targets and Regulatory Functions of N 6-Methyladenosine (m6A) Writers and Erasers.

Currently, although many successful bioinformatics efforts have been reported in the epitranscriptomics field for N 6-methyladenosine (m6A) site identification, none is focused on the substrate specificity of different m6A-related enzymes, ie, the methyltransferases (writers) and demethylases (erasers). In this work, to untangle the target specificity and the regulatory functions of different RNA m6A writers (METTL3-METT14 and METTL16) and erasers (ALKBH5 and FTO), we extracted 49 genomic features along with the conventional sequence features and used the machine learning approach of random forest to predict their epitranscriptome substrates. Our method achieved reasonable performance on both the writer target prediction (as high as 0.918) and the eraser target prediction (as high as 0.888) in a 5-fold cross-validation, and results of the gene ontology analysis of their preferential targets further revealed the functional relevance of different RNA methylation writers and erasers.