XB-ART-59154
Nat Methods
2022 Jul 01;197:833-844. doi: 10.1038/s41592-022-01513-3.
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Direct identification of A-to-I editing sites with nanopore native RNA sequencing.
Nguyen TA
,
Heng JWJ
,
Kaewsapsak P
,
Kok EPL
,
Stanojević D
,
Liu H
,
Cardilla A
,
Praditya A
,
Yi Z
,
Lin M
,
Aw JGA
,
Ho YY
,
Peh KLE
,
Wang Y
,
Zhong Q
,
Heraud-Farlow J
,
Xue S
,
Reversade B
,
Walkley C
,
Ho YS
,
Šikić M
,
Wan Y
,
Tan MH
.
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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.
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???displayArticle.grants??? [+]
NMRC/OFIRG/0017/2016 MOH | National Medical Research Council (NMRC), Global Investigatorship European Molecular Biology Organization (EMBO), NRF2017-NRF-ISF002-2673 National Research Foundation Singapore (National Research Foundation-Prime Minister's office, Republic of Singapore), ASPIRE League seed grant Nanyang Technological University (NTU), FYP fund Nanyang Technological University (NTU), iGEM fund Nanyang Technological University (NTU), Ph.D. research scholarship Nanyang Technological University (NTU), Core funds Genome Institute of Singapore (GIS)
Genes referenced: adar
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