Detecting RNA modifications from nanopore ionic current signals

Abstract

To date, over 150 naturally occurring RNA modifications have been identified. Oxford Nanopore’s direct RNA technology senses RNA molecules directly, permitting RNA modification detection during sequencing. Presently, Guppy cannot always accurately interpret the signals of modified nucleotides, leading to errors. We developed Nanocompore that compares ionic current signals from two different samples to detect modified nucleotides agnostic of basecalling training. We tested Nanocompore using several datasets and find that our results correlate with other RNA modification detection methods, confirm previous observations on the distribution of N6-methyladenosine sites, and provide insights into the distribution of RNA modifications in coding and non-coding transcripts.