Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350004, China; Department of Mathematical Sciences, Xi'an Jiaotong-Liverpool University, Suzhou 215123, China; Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool L69 7ZB, United Kingdom.
Department of Biological Sciences, Xi'an Jiaotong-Liverpool University, Suzhou 215123, China; Department of Computer Science, University of Liverpool, Liverpool L69 7ZB, United Kingdom.
Genomics Proteomics Bioinformatics. 2023 Aug;21(4):678-694. doi: 10.1016/j.gpb.2022.09.001. Epub 2022 Sep 9.
As the most pervasive epigenetic marker present on mRNAs and long non-coding RNAs (lncRNAs), N-methyladenosine (mA) RNA methylation has been shown to participate in essential biological processes. Recent studies have revealed the distinct patterns of mA methylome across human tissues, and a major challenge remains in elucidating the tissue-specific presence and circuitry of mA methylation. We present here a comprehensive online platform, m6A-TSHub, for unveiling the context-specific mA methylation and genetic mutations that potentially regulate mA epigenetic mark. m6A-TSHub consists of four core components, including (1) m6A-TSDB, a comprehensive database of 184,554 functionally annotated mA sites derived from 23 human tissues and 499,369 mA sites from 25 tumor conditions, respectively; (2) m6A-TSFinder, a web server for high-accuracy prediction of mA 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 mA 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 mA modifications in the primary tissue of cancers. The database should make a useful resource for studying the mA 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.
作为存在于 mRNA 和长链非编码 RNA（lncRNA）上最普遍的表观遗传标记，N6-甲基腺苷（m6A）RNA 甲基化被证明参与了重要的生物学过程。最近的研究揭示了 m6A 甲基组在人类组织中的独特模式，阐明 m6A 甲基化的组织特异性存在和调控机制仍然是一个主要挑战。我们在此介绍了一个全面的在线平台 m6A-TSHub，用于揭示潜在调节 m6A 表观遗传标记的特定组织中 m6A 甲基化和遗传突变的上下文特异性。m6A-TSHub 由四个核心组件组成，包括（1）m6A-TSDB，一个综合数据库，包含分别来自 23 个人类组织和 25 种肿瘤条件的 184554 个功能注释 m6A 位点和 499369 个 m6A 位点；（2）m6A-TSFinder，一个用于从 RNA 序列中高精度预测特定组织内 m6A 甲基化位点的网络服务器，该服务器是使用具有门控注意力的多实例深度神经网络构建的；（3）m6A-TSVar，一个用于评估遗传变异对组织特异性 m6A RNA 修饰影响的网络服务器；（4）m6A-CAVar，一个包含 587983 个癌症基因组图谱（TCGA）癌症突变（源自 27 种癌症类型）的数据库，这些突变被预测会影响癌症原发组织中的 m6A 修饰。该数据库将成为研究特定组织（或癌症类型）中 m6A 甲基组和遗传因素对转录后修饰干扰的有用资源。m6A-TSHub 可在 www.xjtlu.edu.cn/biologicalsciences/m6ats 访问。
