Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/162250
Title: Direct identification of A-to-I editing sites with nanopore native RNA sequencing
Authors: Nguyen, Tram Anh
Heng, Joel Jia Wei
Kaewsapsak, Pornchai
Kok, Louis Eng Piew
Stanojević, Dominik
Liu, Hao
Cardilla, Angelysia
Praditya, Albert
Yi, Zirong
Lin, Mingwan
Aw, Ashley Jong Ghut
Ho, Yin Ying
Peh, Esther Kai Lay
Wang, Yuanming
Zhong, Qixing
Heraud-Farlow, Jacki
Xue, Shifeng
Reversade, Bruno
Walkley, Carl
Ho, Ying Swan
Šikić, Mile
Wan, Yue
Tan, Meng How
Keywords: Engineering::Bioengineering
Science::Biological sciences
Issue Date: 2022
Source: Nguyen, T. A., Heng, J. J. W., Kaewsapsak, P., Kok, L. E. P., Stanojević, D., Liu, H., Cardilla, A., Praditya, A., Yi, Z., Lin, M., Aw, A. J. G., Ho, Y. Y., Peh, E. K. L., Wang, Y., Zhong, Q., Heraud-Farlow, J., Xue, S., Reversade, B., Walkley, C., ...Tan, M. H. (2022). Direct identification of A-to-I editing sites with nanopore native RNA sequencing. Nature Methods, 19(7), 833-844. https://dx.doi.org/10.1038/s41592-022-01513-3
Project: NRF2017-NRF-ISF002–2673
NMRC/OFIRG/0017/2016
Journal: Nature Methods
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.
URI: https://hdl.handle.net/10356/162250
ISSN: 1548-7091
DOI: 10.1038/s41592-022-01513-3
Rights: © 2022, The Author(s), under exclusive licence to Springer Nature America, Inc. All rights reserved.
Fulltext Permission: none
Fulltext Availability: No Fulltext
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