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ORIGINAL RESEARCH article

Front. Genet.

Sec. RNA

This article is part of the Research TopicEpigenetic Modifications in Drugs and DiseasesView all 5 articles

m6AHD: A new framework for identifying abnormal N6-Methyladenosine (m6A) in heart diseases based on sequencing features

Provisionally accepted
  • 1Department of Hepatobiliary Surgery, Fujian Medical University Union Hospital, Fuzhou, China
  • 2Fujian Medical University School of Medical Technology and Engineering, Fuzhou, China
  • 3Department of Clinical Laboratory, Fujian Medical University Affliated First Quanzhou Hospital, Quanzhou, China

The final, formatted version of the article will be published soon.

Cardiovascular disease (CVD) is a major threat to health, with high incidence rates and a trend toward younger age groups. RNA modifications are an important component of epigenetics, widely present and indispensable in cells. Increasing evidence suggests that RNA modifications are key regulatory factors involved in cardiac physiological and pathological changes. Understanding the role of RNA modifications in heart-related diseases can help us to identify new drug targets. To systematically investigate the role of m6A modification in different cardiac diseases, we integrated m6A epitranscriptome profiles from five cardiac pathological conditions (three drug-induced cardiac toxicity models Evodiamine, Matrine, and TKI, hypertrophy, and heart calcification) and their control groups to construct the first predictive model for abnormal m6A modification in cardiac diseases. We constructed separate models for upregulated and downregulated modifications under different pathological conditions, performed feature selection and parameter optimization, and validated the performance of our models using an independent test set. Cross-validation across different conditions and model interpretability demonstrated that m6A modifications exhibit similar patterns under different pathological conditions and are potentially regulated by similar factors, providing new clues for identifying targets in cardiovascular diseases at the epitranscriptome level. Furthermore, we validated our findings using a zebrafish model of Evodiamine-induced cardiotoxicity. The experimental results revealed significant morphological defects and a broad downregulation of m6A methyltransferase complex components, confirming the involvement of aberrant m6A machinery in the pathology of cardiotoxicity.

Keywords: bioinformatics framework, cardiac disease, M6A, machine learning, RNA modification

Received: 28 Dec 2025; Accepted: 02 Feb 2026.

Copyright: © 2026 Lu, Li, Hong, Liao and Fang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Guanhua Fang

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