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

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          Abstract

          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 (m 6A, m 1A, m 5C, m 5U, m 6Am, m 7G, 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.

          Abstract

          RNA modifications appear to play a role in determining RNA structure and function. Here, the authors develop a deep learning model that predicts the location of 12 RNA modifications using primary sequence, and show that several modifications are associated, which suggests dependencies between them.

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          Most cited references52

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          SMOTE: Synthetic Minority Over-sampling Technique

          An approach to the construction of classifiers from imbalanced datasets is described. A dataset is imbalanced if the classification categories are not approximately equally represented. Often real-world data sets are predominately composed of ``normal'' examples with only a small percentage of ``abnormal'' or ``interesting'' examples. It is also the case that the cost of misclassifying an abnormal (interesting) example as a normal example is often much higher than the cost of the reverse error. Under-sampling of the majority (normal) class has been proposed as a good means of increasing the sensitivity of a classifier to the minority class. This paper shows that a combination of our method of over-sampling the minority (abnormal) class and under-sampling the majority (normal) class can achieve better classifier performance (in ROC space) than only under-sampling the majority class. This paper also shows that a combination of our method of over-sampling the minority class and under-sampling the majority class can achieve better classifier performance (in ROC space) than varying the loss ratios in Ripper or class priors in Naive Bayes. Our method of over-sampling the minority class involves creating synthetic minority class examples. Experiments are performed using C4.5, Ripper and a Naive Bayes classifier. The method is evaluated using the area under the Receiver Operating Characteristic curve (AUC) and the ROC convex hull strategy.
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            UMAP: Uniform Manifold Approximation and Projection

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              MODOMICS: a database of RNA modification pathways. 2017 update

              Abstract MODOMICS is a database of RNA modifications that provides comprehensive information concerning the chemical structures of modified ribonucleosides, their biosynthetic pathways, the location of modified residues in RNA sequences, and RNA-modifying enzymes. In the current database version, we included the following new features and data: extended mass spectrometry and liquid chromatography data for modified nucleosides; links between human tRNA sequences and MINTbase - a framework for the interactive exploration of mitochondrial and nuclear tRNA fragments; new, machine-friendly system of unified abbreviations for modified nucleoside names; sets of modified tRNA sequences for two bacterial species, updated collection of mammalian tRNA modifications, 19 newly identified modified ribonucleosides and 66 functionally characterized proteins involved in RNA modification. Data from MODOMICS have been linked to the RNAcentral database of RNA sequences. MODOMICS is available at http://modomics.genesilico.pl.
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                Author and article information

                Contributors
                daiyun.huang@liverpool.ac.uk
                jia.meng@xjtlu.edu.cn
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                29 June 2021
                29 June 2021
                2021
                : 12
                : 4011
                Affiliations
                [1 ]GRID grid.440701.6, ISNI 0000 0004 1765 4000, Department of Mathematical Sciences, , Xi’an Jiaotong-Liverpool University, ; Suzhou, PR China
                [2 ]GRID grid.440701.6, ISNI 0000 0004 1765 4000, Department of Biological Sciences, , Xi’an Jiaotong-Liverpool University, ; Suzhou, PR China
                [3 ]GRID grid.10025.36, ISNI 0000 0004 1936 8470, Department of Computer Sciences, , University of Liverpool, ; Liverpool, United Kingdom
                [4 ]GRID grid.10025.36, ISNI 0000 0004 1936 8470, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, ; Liverpool, United Kingdom
                [5 ]GRID grid.256112.3, ISNI 0000 0004 1797 9307, Laboratory of Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, ; Fuzhou, PR China
                [6 ]GRID grid.440701.6, ISNI 0000 0004 1765 4000, School of AI and Advanced Computing, XJTLU Entrepreneur College (Taicang), Xi’an Jiaotong-Liverpool University, ; Suzhou, PR China
                [7 ]GRID grid.10025.36, ISNI 0000 0004 1936 8470, Institute of Ageing and Chronic Disease, University of Liverpool, ; Liverpool, United Kingdom
                [8 ]GRID grid.440701.6, ISNI 0000 0004 1765 4000, AI University Research Centre, Xi’an Jiaotong-Liverpool University, ; Suzhou, PR China
                Author information
                http://orcid.org/0000-0003-4646-0339
                http://orcid.org/0000-0002-3067-7165
                http://orcid.org/0000-0002-6363-2465
                http://orcid.org/0000-0003-3455-205X
                Article
                24313
                10.1038/s41467-021-24313-3
                8242015
                34188054
                2fd5c74b-d405-4634-9571-4805d528fb7e
                © The Author(s) 2021

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 21 November 2020
                : 7 June 2021
                Funding
                Funded by: XJTLU Key Program Special Fund [KSF-T-01]
                Categories
                Article
                Custom metadata
                © The Author(s) 2021

                Uncategorized
                rna,computational models,machine learning
                Uncategorized
                rna, computational models, machine learning

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