m6AConquer: a consistently quantified and orthogonally validated database for the N6-methyladenosine (m6A) epitranscriptome

Nucleic Acids Res. 2025 Dec 3:gkaf1204. doi: 10.1093/nar/gkaf1204. Online ahead of print.

ABSTRACT

The proper placement of N6-methyladenosine (m6A) on mRNA is essential for normal cell function, and its disruption is linked to numerous human diseases. The rapid growth of m6A data from diverse sequencing technologies presents challenges for integrative analysis due to technique-specific biases and inconsistent processing. While existing databases provide valuable catalogs, their reliance on aggregating pre-processed results can propagate inconsistencies. To overcome these limitations, we present m6AConquer, a database founded on reproducible quantification. We systematically re-processed raw data from 10 distinct profiling methods, including high-resolution GLORI and eTAM-seq, quantifying methylation at millions of consensus sites across human and mouse. Our rigorous pipeline features uniform site-calling and false-positive calibration with in vitro transcribed (IVT) controls where available. By leveraging a reproducibility-based framework across technically orthogonal methods, we identified over 135300 orthogonally validated m6A sites in human (IDR < 0.05). Beyond this validated methylome, m6AConquer provides matched multi-omics data (gene expression, splicing, variants) and identifies m6A quantitative trait loci (m6A QTLs) to link RNA modification to genetic regulation and disease. Offering intuitive query tools, interactive visualizations, and downloadable, analysis-ready data matrices, m6AConquer provides a standardized resource for rigorous exploration of the roles of m6A in biology and medicine, freely accessible at https://rnamd.org/m6aconquer/.

PMID:41330425 | DOI:10.1093/nar/gkaf1204