De novo basecalling of RNA modifications at single molecule and nucleotide resolution

在单分子和核苷酸分辨率下对 RNA 修饰进行从头碱基调用

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作者:Sonia Cruciani #, Anna Delgado-Tejedor #, Leszek P Pryszcz #, Rebeca Medina, Laia Llovera, Eva Maria Novoa

Abstract

RNA modifications influence RNA function and fate, but detecting them in individual molecules remains challenging for most modifications. Here we present a novel methodology to generate training sets and build modification-aware basecalling models. Using this approach, we develop the m6ABasecaller, a basecalling model that predicts m6A modifications from raw nanopore signals. We validate its accuracy in vitro and in vivo, revealing stable m6A modification stoichiometry across isoforms, m6A co-occurrence within RNA molecules, and m6A-dependent effects on poly(A) tails. Finally, we demonstrate that our method generalizes to other RNA and DNA modifications, paving the path towards future efforts detecting other modifications.

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