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

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

Izvornik
Nature methods (1548-7091) 19 (2022); 833-844

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
inosine, RNA modification, prediction, sequencing

Sažetak
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.

Izvorni jezik
Engleski

Znanstvena područja
Računarstvo

POVEZANOST RADA