Direct identification of A-to-I editing sites with nanopore native RNA sequencing

Tram Anh Nguyen, Jia Wei Joel Heng, Pornchai Kaewsapsak, Eng Piew Louis Kok, Dominik Stanojević, Hao Liu, Angelysia Cardilla, Albert Praditya, Zirong Yi, Mingwan Lin, Jong Ghut Ashley Aw, Yin Ying Ho, Kai Lay Esther Peh, Yuanming Wang, Qixing Zhong, Jacki Heraud-Farlow, Shifeng Xue, Bruno Reversade, Carl Walkley, Ying Swan HoMile Šikić, Yue Wan, Meng How Tan

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Inosine is a prevalent RNA modification in animals and is formed when an adenosine is deaminated by the ADAR family of enzymes. Traditionally, inosines are identified indirectly as variants from Illumina RNA-sequencing data because they are interpreted as guanosines by cellular machineries. However, this indirect method performs poorly in protein-coding regions where exons are typically short, in non-model organisms with sparsely annotated single-nucleotide polymorphisms, or in disease contexts where unknown DNA mutations are pervasive. Here, we show that Oxford Nanopore direct RNA sequencing can be used to identify inosine-containing sites in native transcriptomes with high accuracy. We trained convolutional neural network models to distinguish inosine from adenosine and guanosine, and to estimate the modification rate at each editing site. Furthermore, we demonstrated their utility on the transcriptomes of human, mouse and Xenopus. Our approach expands the toolkit for studying adenosine-to-inosine editing and can be further extended to investigate other RNA modifications.
Original languageEnglish (US)
Pages (from-to)833-844
Number of pages12
JournalNature Methods
Volume19
Issue number7
DOIs
StatePublished - Jul 1 2022
Externally publishedYes

Bibliographical note

Generated from Scopus record by KAUST IRTS on 2023-02-15

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Biotechnology

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