Accurate detection of m6A RNA modifications in native RNA sequences

Liu, Huanle; Begik, Oguzhan; Lucas, Morghan C.; Ramirez, Jose Miguel; Mason, Christopher E.; Wiener, David; Schwartz, Schraga; Mattick, John S.; Smith, Martin A.; Novoa, Eva Maria

doi:http://dx.doi.org/10.1038/s41467-019-11713-9

Accurate detection of m6A RNA modifications in native RNA sequences

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Liu H, Begik O, Lucas MC, Ramirez JM, Mason CE, Wiener D, Schwartz S, Mattick JS, Smith MA, Novoa EM. Accurate detection of m6A RNA modifications in native RNA sequences. Nat Commun. 2019; 10(1):4079. DOI: 10.1038/s41467-019-11713-9

Abstract

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.