Faculty of Computer Science, Deggendorf Institute of Technology, Dieter-Görlitz-Platz 1, Deggendorf, 94469, Bavaria, Germany.
Department for Pediatric Hematology, Oncology and Stem Cell Transplantation, University Hospital Regensburg, Franz-Josef-Strauß-Allee 11, Regensbug, 93053, Bavaria, Germany.
Nat Commun. 2024 Oct 23;15(1):9121. doi: 10.1038/s41467-024-53298-y.
RNA editing is a highly conserved process. Adenosine deaminase acting on RNA (ADAR) mediated deamination of adenosine (A-to-I editing) is associated with human disease and immune checkpoint control. Functional implications of A-to-I editing are currently of broad interest to academic and industrial research as underscored by the fast-growing number of clinical studies applying base editors as therapeutic tools. Analyzing the dynamics of A-to-I editing, in a biological or therapeutic context, requires the sensitive detection of differential A-to-I editing, a currently unmet need. We introduce the local differential editing index (LoDEI) to detect differential A-to-I editing in RNA-seq datasets using a sliding-window approach coupled with an empirical q value calculation that detects more A-to-I editing sites at the same false-discovery rate compared to existing methods. LoDEI is validated on known and novel datasets revealing that the oncogene MYCN increases and that a specific small non-coding RNA reduces A-to-I editing.
RNA 编辑是一种高度保守的过程。腺苷脱氨酶作用于 RNA（ADAR）介导的腺苷脱氨（A-to-I 编辑）与人类疾病和免疫检查点控制有关。A-to-I 编辑的功能意义目前受到学术和工业研究的广泛关注，这突出体现在越来越多的临床研究将碱基编辑器作为治疗工具应用。在生物学或治疗学背景下分析 A-to-I 编辑的动态，需要灵敏地检测到差异的 A-to-I 编辑，这是当前尚未满足的需求。我们引入了局部差异编辑指数（LoDEI），通过滑动窗口方法结合经验 q 值计算来检测 RNA-seq 数据集中的差异 A-to-I 编辑，与现有方法相比，该方法可以在相同的错误发现率下检测到更多的 A-to-I 编辑位点。LoDEI 在已知和新的数据集上得到验证，结果表明致癌基因 MYCN 增加，而特定的小非编码 RNA 减少 A-to-I 编辑。
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