State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing 100875, China.
BABRI Centre, Beijing Normal University, Beijing 100875, China.
Biomed Res Int. 2020 Mar 26;2020:8348147. doi: 10.1155/2020/8348147. eCollection 2020.
Alzheimer's disease (AD) is a neurodegenerative disorder and characterized by the cognitive impairments. It is essential to identify potential gene biomarkers for AD pathology.
DNA methylation expression data of patients with AD were downloaded from the Gene Expression Omnibus (GEO) database. Differentially methylated sites were identified. The functional annotation analysis of corresponding genes in the differentially methylated sites was performed. The optimal diagnostic gene biomarkers for AD were identified by using random forest feature selection procedure. In addition, receiver operating characteristic (ROC) diagnostic analysis of differentially methylated genes was performed.
A total of 10 differentially methylated sites including 5 hypermethylated sites and 5 hypomethylated sites were identified in AD. There were a total of 8 genes including thioredoxin interacting protein (TXNIP), noggin (NOG), regulator of microtubule dynamics 2 (FAM82A1), myoneurin (MYNN), ankyrin repeat domain 34B (ANKRD34B), STAM-binding protein like 1, ALMalpha (STAMBPL1), cyclin-dependent kinase inhibitor 1C (CDKN1C), and coronin 2B (CORO2B) that correspond to 10 differentially methylated sites. The cell cycle (FDR = 0.0284087) and TGF-beta signaling pathway (FDR = 0.0380372) were the only two significantly enriched pathways of these genes. MYNN was selected as optimal diagnostic biomarker with great diagnostic value. The random forests model could effectively predict AD.
Our study suggested that MYNN could be served as optimal diagnostic biomarker of AD. Cell cycle and TGF-beta signaling pathway may be associated with AD.
阿尔茨海默病（AD）是一种神经退行性疾病，其特征是认知障碍。识别潜在的 AD 病理基因生物标志物至关重要。
从基因表达综合数据库（GEO）下载 AD 患者的 DNA 甲基化表达数据。鉴定差异甲基化位点。对差异甲基化位点中相应基因进行功能注释分析。通过随机森林特征选择程序，确定 AD 的最佳诊断基因生物标志物。此外，还对差异甲基化基因进行了接收者操作特征（ROC）诊断分析。
在 AD 中鉴定出 10 个差异甲基化位点，包括 5 个高甲基化位点和 5 个低甲基化位点。共有 8 个基因，包括硫氧还蛋白相互作用蛋白（TXNIP）、noggin（NOG）、微管动力学调节因子 2（FAM82A1）、myoneurin（MYNN）、ankyrin 重复结构域 34B（ANKRD34B）、STAM 结合蛋白样 1（STAMBPL1）、细胞周期蛋白依赖性激酶抑制剂 1C（CDKN1C）和 coronin 2B（CORO2B），与 10 个差异甲基化位点相对应。这些基因中唯一显著富集的通路只有细胞周期（FDR = 0.0284087）和 TGF-β 信号通路（FDR = 0.0380372）。MYNN 被选为具有较大诊断价值的最佳诊断生物标志物。随机森林模型可以有效地预测 AD。
我们的研究表明，MYNN 可以作为 AD 的最佳诊断生物标志物。细胞周期和 TGF-β 信号通路可能与 AD 有关。
