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Direct identification of A-to-I editing sites with nanopore native RNA sequencing
Nguyen, Tram Heng, Jia Kaewsapsak, Pornchai Kok, Eng Stanojevic, Dominik Liu, Hao Cardilla, Angelysia Praditya, Albert Yi, Zirong Lin, Mingwan
Nguyen, Tram
Heng, Jia
Kaewsapsak, Pornchai
Kok, Eng
Stanojevic, Dominik
Liu, Hao
Cardilla, Angelysia
Praditya, Albert
Yi, Zirong
Lin, Mingwan
Author
Nguyen, Tram
Heng, Jia
Kaewsapsak, Pornchai
Kok, Eng
Stanojevic, Dominik
Liu, Hao
Cardilla, Angelysia
Praditya, Albert
Yi, Zirong
Lin, Mingwan
Aw, Jong
Ho, Yin
Peh, Kai
Wang, Yuanming
Zhong, Qixing
Heraud-Farlow, Jacki
Xue, Shifeng
Reversade, Bruno
Walkley, Carl Richard
Ho, Ying
Sikic, Mile
Wan, Yue
Tan, Meng
Heng, Jia
Kaewsapsak, Pornchai
Kok, Eng
Stanojevic, Dominik
Liu, Hao
Cardilla, Angelysia
Praditya, Albert
Yi, Zirong
Lin, Mingwan
Aw, Jong
Ho, Yin
Peh, Kai
Wang, Yuanming
Zhong, Qixing
Heraud-Farlow, Jacki
Xue, Shifeng
Reversade, Bruno
Walkley, Carl Richard
Ho, Ying
Sikic, Mile
Wan, Yue
Tan, Meng
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.
Keywords
Adenosine genetics, Animals, Inosine genetics, Mice, Nanopores, RNA Editing, RNA genetics, RNA metabolism, Sequence Analysis
Date
2022
Type
Journal article
Journal
Book
Volume
19
Issue
Page Range
833-844
Article Number
ACU Department
Mary MacKillop Institute for Health Research
Faculty of Health Sciences
Faculty of Health Sciences
Collections
Relation URI
Event URL
Open Access Status
License
All rights reserved
File Access
Controlled
Notes
© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.