m6A-TSHub: Unveiling the Context-specific m6A Methylation and m6A-affecting Mutations in 23 Human Tissues.

Abstract

As the most pervasive epigenetic marker present on mRNAs and long non-coding RNAs (lncRNAs), N⁶-methyladenosine (m⁶A) RNA methylation has been shown to participate in essential biological processes. Recent studies have revealed the distinct patterns of m⁶A methylome across human tissues, and a major challenge remains in elucidating the tissue-specific presence and circuitry of m⁶A methylation. We present here a comprehensive online platform, m6A-TSHub, for unveiling the context-specific m⁶A methylation and genetic mutations that potentially regulate m⁶A epigenetic mark. m6A-TSHub consists of four core components, including (1) m6A-TSDB, a comprehensive database of 184,554 functionally annotated m⁶A sites derived from 23 human tissues and 499,369 m⁶A sites from 25 tumor conditions, respectively; (2) m6A-TSFinder, a web server for high-accuracy prediction of m⁶A methylation sites within a specific tissue from RNA sequences, which was constructed using multi-instance deep neural networks with gated attention; (3) m6A-TSVar, a web server for assessing the impact of genetic variants on tissue-specific m⁶A RNA modifications; and (4) m6A-CAVar, a database of 587,983 The Cancer Genome Atlas (TCGA) cancer mutations (derived from 27 cancer types) that were predicted to affect m⁶A modifications in the primary tissue of cancers. The database should make a useful resource for studying the m⁶A methylome and the genetic factors of epitranscriptome disturbance in a specific tissue (or cancer type). m6A-TSHub is accessible at www.xjtlu.edu.cn/biologicalsciences/m6ats.