Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung, 40402, Taiwan.
Department of Medical Research, China Medical University Hospital, Taichung, 40447, Taiwan.
Sci Rep. 2023 Aug 23;13(1):13805. doi: 10.1038/s41598-023-40879-y.
Amyotrophic lateral sclerosis (ALS), the most prevalent motor neuron disease characterized by its complex genetic structure, lacks a single diagnostic test capable of providing a conclusive diagnosis. In order to demonstrate the potential for genetic diagnosis and shed light on the pathogenic role of miRNAs in ALS, we developed an ALS diagnostic rule by training the model using 80% of a miRNA profiling dataset consisting of 253 ALS samples and 103 control samples. Subsequently, we validated the diagnostic rule using the remaining 20% of unseen samples. The diagnostic rule we developed includes miR-205-5p, miR-206, miR-376a-5p, miR-412-5p, miR-3927-3p, miR-4701-3p, miR-6763-5p, and miR-6801-3p. Remarkably, the rule achieved an 82% true positive rate and a 73% true negative rate when predicting the unseen samples. Furthermore, the identified miRNAs target 21 genes in the PI3K-Akt pathway and 27 genes in the ALS pathway, including notable genes such as BCL2, NEFH, and OPTN. We propose that miRNA profiling may serve as a complementary diagnostic tool to supplement the clinical presentation and aid in the early recognition of ALS.
肌萎缩侧索硬化症（ALS）是最常见的运动神经元疾病，其特征是具有复杂的遗传结构，目前缺乏一种能够提供明确诊断的单一诊断测试。为了展示遗传诊断的潜力，并阐明 miRNA 在 ALS 中的致病作用，我们使用由 253 个 ALS 样本和 103 个对照样本组成的 miRNA 图谱数据集的 80%来训练模型，从而制定了一个 ALS 诊断规则。随后，我们使用其余 20%的未见样本对该诊断规则进行了验证。我们开发的诊断规则包括 miR-205-5p、miR-206、miR-376a-5p、miR-412-5p、miR-3927-3p、miR-4701-3p、miR-6763-5p 和 miR-6801-3p。值得注意的是，当预测未见样本时，该规则的真阳性率为 82%，真阴性率为 73%。此外，鉴定出的 miRNA 靶向 PI3K-Akt 通路中的 21 个基因和 ALS 通路中的 27 个基因，包括 BCL2、NEFH 和 OPTN 等重要基因。我们提出 miRNA 图谱分析可能作为一种补充性诊断工具，以补充临床表现，并有助于早期识别 ALS。
