R2Dtool: Integration and Visualization of Isoform-resolved RNA Features

Overview

Journal Bioinformatics

Publisher Oxford University Press

Specialty Biology

Date 2024 Aug 7

PMID 39110520

Authors

Aditya J Sethi

Pablo Acera Mateos

Rippei Hayashi

Nikolay E Shirokikh

Eduardo Eyras

Affiliations

Soon will be listed here.

Abstract

Motivation: Long-read RNA sequencing enables the mapping of RNA modifications, structures, and protein-interaction sites at the resolution of individual transcript isoforms. To understand the functions of these RNA features, it is critical to analyze them in the context of transcriptomic and genomic annotations, such as open reading frames and splice junctions.

Results: We have developed R2Dtool, a bioinformatics tool that integrates transcript-mapped information with transcript and genome annotations, allowing for the isoform-resolved analytics and graphical representation of RNA features in their genomic context. We illustrate R2Dtool's capability to integrate and expedite RNA feature analysis using epitranscriptomics data. R2Dtool facilitates the comprehensive analysis and interpretation of alternative transcript isoforms.

Availability And Implementation: R2Dtool is freely available under the MIT license at github.com/comprna/R2Dtool.

Citing Articles

Prediction of m6A and m5C at single-molecule resolution reveals a transcriptome-wide co-occurrence of RNA modifications.

Acera Mateos P, J Sethi A, Ravindran A, Srivastava A, Woodward K, Mahmud S Nat Commun. 2024; 15(1):3899.

PMID: 38724548 PMC: 11082244. DOI: 10.1038/s41467-024-47953-7.

References

Acera Mateos P, J Sethi A, Ravindran A, Srivastava A, Woodward K, Mahmud S . Prediction of m6A and m5C at single-molecule resolution reveals a transcriptome-wide co-occurrence of RNA modifications. Nat Commun. 2024; 15(1):3899. PMC: 11082244. DOI: 10.1038/s41467-024-47953-7. View

Lee Y, Choe J, Park O, Kim Y . Molecular Mechanisms Driving mRNA Degradation by mA Modification. Trends Genet. 2020; 36(3):177-188. DOI: 10.1016/j.tig.2019.12.007. View

Aw J, Lim S, Wang J, Lambert F, Tan W, Shen Y . Determination of isoform-specific RNA structure with nanopore long reads. Nat Biotechnol. 2020; 39(3):336-346. DOI: 10.1038/s41587-020-0712-z. View

Uzonyi A, Dierks D, Nir R, Kwon O, Toth U, Barbosa I . Exclusion of m6A from splice-site proximal regions by the exon junction complex dictates m6A topologies and mRNA stability. Mol Cell. 2023; 83(2):237-251.e7. DOI: 10.1016/j.molcel.2022.12.026. View

Van Nostrand E, Pratt G, Yee B, Wheeler E, Blue S, Mueller J . Principles of RNA processing from analysis of enhanced CLIP maps for 150 RNA binding proteins. Genome Biol. 2020; 21(1):90. PMC: 7137325. DOI: 10.1186/s13059-020-01982-9. View

Tapial J, Ha K, Sterne-Weiler T, Gohr A, Braunschweig U, Hermoso-Pulido A . An atlas of alternative splicing profiles and functional associations reveals new regulatory programs and genes that simultaneously express multiple major isoforms. Genome Res. 2017; 27(10):1759-1768. PMC: 5630039. DOI: 10.1101/gr.220962.117. View

Quinlan A . BEDTools: The Swiss-Army Tool for Genome Feature Analysis. Curr Protoc Bioinformatics. 2014; 47:11.12.1-34. PMC: 4213956. DOI: 10.1002/0471250953.bi1112s47. View

Thorvaldsdottir H, Robinson J, Mesirov J . Integrative Genomics Viewer (IGV): high-performance genomics data visualization and exploration. Brief Bioinform. 2012; 14(2):178-92. PMC: 3603213. DOI: 10.1093/bib/bbs017. View

Lin Y, Kwok S, Hein A, Thai B, Alabi Y, Ostrowski M . RNA molecular recording with an engineered RNA deaminase. Nat Methods. 2023; 20(12):1887-1899. PMC: 11497829. DOI: 10.1038/s41592-023-02046-z. View

10.

Olarerin-George A, Jaffrey S . MetaPlotR: a Perl/R pipeline for plotting metagenes of nucleotide modifications and other transcriptomic sites. Bioinformatics. 2017; 33(10):1563-1564. PMC: 5860047. DOI: 10.1093/bioinformatics/btx002. View

11.

Pertea G, Pertea M . GFF Utilities: GffRead and GffCompare. F1000Res. 2020; 9. PMC: 7222033. DOI: 10.12688/f1000research.23297.2. View

12.

Dominissini D, Moshitch-Moshkovitz S, Schwartz S, Salmon-Divon M, Ungar L, Osenberg S . Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq. Nature. 2012; 485(7397):201-6. DOI: 10.1038/nature11112. View

13.

Liu H, Begik O, Lucas M, Ramirez J, Mason C, Wiener D . Accurate detection of mA RNA modifications in native RNA sequences. Nat Commun. 2019; 10(1):4079. PMC: 6734003. DOI: 10.1038/s41467-019-11713-9. View

14.

Stephenson W, Razaghi R, Busan S, Weeks K, Timp W, Smibert P . Direct detection of RNA modifications and structure using single-molecule nanopore sequencing. Cell Genom. 2022; 2(2). PMC: 8896822. DOI: 10.1016/j.xgen.2022.100097. View

15.

Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N . The Sequence Alignment/Map format and SAMtools. Bioinformatics. 2009; 25(16):2078-9. PMC: 2723002. DOI: 10.1093/bioinformatics/btp352. View

16.

Hendra C, Pratanwanich P, Kei Wan Y, Goh W, Thiery A, Goke J . Detection of m6A from direct RNA sequencing using a multiple instance learning framework. Nat Methods. 2022; 19(12):1590-1598. PMC: 9718678. DOI: 10.1038/s41592-022-01666-1. View