纳米孔RNA测序可直接检测A-to-I的编辑位点
2022-06-19   阅读:650   来源:自然

新加坡南洋理工大学Meng How Tan课题组发现,纳米孔RNA测序可直接检测A-to-I的编辑位点。2022年6月13日,《自然—方法学》杂志在线发表了这项成果。

研究人员发现,牛津纳米孔直接RNA测序可用于识别转录组中的含肌苷位点,且准确度高。研究人员训练了卷积神经网络模型来区分肌苷与腺苷和鸟苷,并估计每个编辑位点的修改率。此外,研究人员在人类、小鼠和爪蟾的转录组上证明了它们的效用。这个方法扩大了研究腺苷到肌苷(A-to-I)编辑的工具箱,并可进一步扩展到研究其他RNA修饰。

据了解,肌苷是动物中普遍存在的一种RNA修饰,当腺苷被ADAR家族的酶脱氨后形成。传统上,肌苷是由Illumina RNA测序数据间接识别的变体,因为它们被细胞机器解读为鸟苷。然而,这种间接方法在外显子通常较短的蛋白质编码区、具有稀少注释的单核苷酸多态性的非模型生物中,或在未知DNA突变普遍存在的疾病背景下表现不佳。

附:英文原文

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

Author: Nguyen, Tram Anh, Heng, Jia Wei Joel, Kaewsapsak, Pornchai, Kok, Eng Piew Louis, Stanojevi, 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, iki, Mile, Wan, Yue, Tan, Meng How

Issue&Volume: 2022-06-13

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. 

DOI: 10.1038/s41592-022-01513-3

编辑:小柯机器人

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