Key Laboratory of Information Fusion Technology of Ministry of Education, School of Automation, Northwestern Polytechnical University, Xi'an, Shaanxi 710027, China.
Key Laboratory of Information Fusion Technology of Ministry of Education, School of Automation, Northwestern Polytechnical University, Xi'an, Shaanxi 710027, China.
Methods. 2022 Jul;203:167-178. doi: 10.1016/j.ymeth.2022.03.008. Epub 2022 Mar 18.
N-methyladenosine (mA) is the most abundant form of mRNA modification and plays an important role in regulating gene expression. However, the mechanisms of mA regulated gene expression in cell or condition specific, are still poorly understood. Even though, some methods are able to predict mA regulated expression (mA-reg-exp) genes in specific context, they don't introduce the mA reader binding information, while this information can help to predict mA-reg-exp genes and more clearly to explain the mechanisms of mA-mediated gene expression process. Thus, by integrating mA sites and reader binding information, we proposed a novel method (called mAexpress-Reader) to predict mA-reg-exp genes from limited MeRIP-seq data in specific context. mAexpress-Reader adopts the reader binding signal strength to weight the posterior distribution of the estimated regulatory coefficients for enhancing the prediction power. By using mAexpress-Reader, we found the complex characteristic of mA on gene expression regulation and the distinct regulated pattern of mA-reg-exp genes with different reader binding. mA readers, YTHDF2 or IGF2BP1/3 all play an important role in various cancers and the key cancer pathways. In addition, mAexpress-Reader reveals the distinct mA regulated mode of reader targeted genes in cancer. mAexpress-Reader could be a useful tool for studying the mA regulation on reader target genes in specific context and it can be freely accessible at: https://github.com/NWPU-903PR/m6AexpressReader.
N6-甲基腺苷（m6A）是 mRNA 修饰中最丰富的形式，在调节基因表达中发挥着重要作用。然而，m6A 调节基因表达的机制在细胞或条件特异性中仍然知之甚少。尽管有些方法能够预测特定环境下的 m6A 调节表达（m6A-reg-exp）基因，但它们没有引入 m6A 读取器结合信息，而这些信息可以帮助预测 m6A-reg-exp 基因，并更清楚地解释 m6A 介导的基因表达过程的机制。因此，通过整合 m6A 位点和读取器结合信息，我们提出了一种新的方法（称为 mAexpress-Reader），用于从特定环境中有限的 MeRIP-seq 数据中预测 m6A-reg-exp 基因。mAexpress-Reader 采用读取器结合信号强度对估计的调控系数的后验分布进行加权，以增强预测能力。通过使用 mAexpress-Reader，我们发现了 m6A 对基因表达调控的复杂特征以及具有不同读取器结合的 m6A-reg-exp 基因的独特调控模式。m6A 读取器 YTHDF2 或 IGF2BP1/3 在各种癌症和关键癌症途径中都发挥着重要作用。此外，mAexpress-Reader 揭示了癌症中读者靶向基因的独特 m6A 调控模式。mAexpress-Reader 可以成为研究特定环境下读者靶向基因的 m6A 调控的有用工具，可在 https://github.com/NWPU-903PR/m6AexpressReader 上免费获取。
