Accurate detection of m6A RNA modifications in native RNA sequences

By Huanle Liu, Oguzhan Begik, M. Lucas, J. Ramirez, Christopher E. Mason, David Wiener, Schraga Schwartz, John S. Mattick, Martin A. Smith, E. Novoa. Nature Communications, 2019

471 citations recorded by the source corpus.

The epitranscriptomics field has undergone an enormous expansion in the last few years; however, a major limitation is the lack of generic methods to map RNA modifications transcriptome-wide. Here, we show that using direct RNA sequencing, N6-methyladenosine (m6A) RNA modifications can be detected with high accuracy, in the form of systematic errors and decreased base-calling qualities. Specifically, we find that our algorithm, trained with m6A-modified and unmodified synthetic sequences, can predict m6A RNA modifications with ~90% accuracy. We then extend our findings to yeast data sets, finding that our method can identify m6A RNA modifications in vivo with an accuracy of 87%. Moreover, we further validate our method by showing that these ‘errors’ are typically not observed in yeast ime4-knockout strains, which lack m6A modifications. Our results open avenues to investigate the biological roles of RNA modifications in their native RNA context. We currently lack generic methods to map RNA modifications across the entire transcriptome. Here, the authors demonstrate that m6A RNA modifications can be detected with high accuracy using nanopore direct RNA sequencing.

Subfields: Cancer Research, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/05882211cb3bdff79bddee7b8a0965c82c3263ba

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In Molecular Biology

Citations in the corpus

Long-read human genome sequencing and its applications (2020, unknown): “54 , Springer Nature Limited. the modified base as it translocates through the nano-pore 86,126,127,142 .”
Nanopore sequencing technology, bioinformatics and applications (2021, background): “Since then, epitranscriptome analyses using ONT sequencing have progressed rapidly, including detection of 7-methylguanosine (m 7 G) and pseudouridine in 16S rRNAs of E. coli 183 , m 6 A in mRNAs of S. cerevisiae 73 and A. thaliana 168 and m 6 A 130 and pseudouridine 104 in human RNAs.”