School of Life Science and Technology, Xidian University, Xi'an, China.
Tongji University, China.
Brief Bioinform. 2021 Sep 2;22(5). doi: 10.1093/bib/bbaa384.
A-to-I RNA editing, contributing to nearly 90% of all editing events in human, has been reported to involve in the pathogenesis of Alzheimer's disease (AD) due to its roles in brain development and immune regulation, such as the deficient editing of GluA2 Q/R related to cell death and memory loss. Currently, there are urgent needs for the systematic annotations of A-to-I RNA editing events in AD. Here, we built ADeditome, the annotation database of A-to-I RNA editing in AD available at https://ccsm.uth.edu/ADeditome, aiming to provide a resource and reference for functional annotation of A-to-I RNA editing in AD to identify therapeutically targetable genes in an individual. We detected 1676 363 editing sites in 1524 samples across nine brain regions from ROSMAP, MayoRNAseq and MSBB. For these editing events, we performed multiple functional annotations including identification of specific and disease stage associated editing events and the influence of editing events on gene expression, protein recoding, alternative splicing and miRNA regulation for all the genes, especially for AD-related genes in order to explore the pathology of AD. Combing all the analysis results, we found 108 010 and 26 168 editing events which may promote or inhibit AD progression, respectively. We also found 5582 brain region-specific editing events with potentially dual roles in AD across different brain regions. ADeditome will be a unique resource for AD and drug research communities to identify therapeutically targetable editing events. Significance: ADeditome is the first comprehensive resource of the functional genomics of individual A-to-I RNA editing events in AD, which will be useful for many researchers in the fields of AD pathology, precision medicine, and therapeutic researches.
A-to-I RNA 编辑，在人类中约有 90%的编辑事件涉及其中，由于其在大脑发育和免疫调节中的作用，如 GluA2 Q/R 相关的编辑缺陷与细胞死亡和记忆丧失有关，据报道与阿尔茨海默病 (AD) 的发病机制有关。目前，迫切需要对 AD 中的 A-to-I RNA 编辑事件进行系统注释。在这里，我们构建了 ADeditome，这是一个可在 https://ccsm.uth.edu/ADeditome 上访问的 AD 中 A-to-I RNA 编辑注释数据库，旨在为 AD 中 A-to-I RNA 编辑的功能注释提供资源和参考，以识别个体中具有治疗潜力的靶基因。我们在 9 个大脑区域的 1524 个样本中检测到了 1676363 个编辑位点来自 ROSMAP、MayoRNAseq 和 MSBB。对于这些编辑事件，我们进行了多种功能注释，包括鉴定特定的和疾病阶段相关的编辑事件，以及编辑事件对所有基因的基因表达、蛋白质重编码、选择性剪接和 miRNA 调节的影响，特别是对于 AD 相关基因，以探索 AD 的病理学。结合所有分析结果，我们发现了 108010 个和 26168 个可能分别促进或抑制 AD 进展的编辑事件。我们还发现了 5582 个具有跨不同大脑区域潜在双重作用的大脑区域特异性编辑事件。ADeditome 将成为 AD 和药物研究社区的独特资源，用于鉴定具有治疗潜力的编辑事件。意义：ADeditome 是 AD 中个体 A-to-I RNA 编辑事件功能基因组学的第一个全面资源，将对 AD 病理学、精准医学和治疗研究领域的许多研究人员有用。
