Pablo Acera Mateos, Aditya J. Sethi, Marco Guarnacci, Agin Ravindran, Akanksha Srivastava, Jiajia Xu, Katrina Woodward, William Hamilton, Jing Gao, Lora M. Starrs, Gaetan Burgio, Rippei Hayashi, Vihandha Wickramasinghe, Nathalie Dehorter, Thomas Preiss, Nikolay Shirokikh, Eduardo Angel Eyras Jiménez
- The expanding field of epitranscriptomics might rival the epigenome in the diversity of the biological processes impacted. However, the identification of modifications in individual RNA molecules remains challenging. We present CHEUI, a new method that detects N6-methyladenosine (m6A) and 5-methylcytidine (m5C) at single-nucleotide and single-molecule resolution from Nanopore signals. CHEUI predicts methylation in Nanopore reads and transcriptomic sites in a single condition, and differential m6A and m5C methylation between any two conditions. Using extensive benchmarking with Nanopore data derived from synthetic and natural RNA, CHEUI showed higher accuracy than other existing methods in detecting m6A and m5C sites and quantifying the site stoichiometry levels, while maintaining a lower proportion of false positives. CHEUI provides a new capability to detect RNA modifications with high accuracy and resolution that can be cost-effectively expanded to other modifications to unveil the full span of the epitranscriptome in normal and disease conditions.
