Identification of Immune Cells and Key Genes associated with Alzheimer's Disease.
Identification of Immune Cells and Key Genes associated with Alzheimer's Disease.
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与阿尔茨海默病相关的免疫细胞和关键基因的鉴定
DOI：
10.7150/ijms.66422
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发表时间：
2022
影响因子：
3.6
通讯作者：
Li S
中科院分区：
文献类型：
--
作者：
Liu C;Zhang X;Chai H;Xu S;Liu Q;Luo Y;Li S
阿尔茨海默病（Alzheimer's disease，AD）是一种以认知功能障碍和记忆丧失为特征的老年性神经退行性疾病，目前尚无有效的治疗方法。在过去的几年中，许多研究表明，AD中炎症的增加是认知障碍的主要原因。本研究旨在揭示与AD相关的22种外周血免疫细胞类型和关键基因。收集基因表达数据库（GEO）中的前额叶皮质转录组数据，采用CIBERSORT方法对所有样本中22种免疫细胞的组成进行分析。采用加权基因共表达网络分析法（WGCNA）构建基因共表达网络，筛选AD相关的候选模块基因。通过构建最小绝对收缩选择算子（LASSO）和随机森林（RF）模型，对从WGCNA结果中筛选出的候选模块基因进行分析。结果表明，AD患者前额叶皮层的免疫浸润与健康人不同。在所有22种免疫细胞中，M1巨噬细胞是与AD最相关的细胞类型。我们通过LASSO和RF分析，发现了10个与AD和M1巨噬细胞相关的关键基因，包括ARMCX5、EDN3、GPR174、MRPL23、RAET1E、ROD1、TRAF1、WNT7B、OR4K2和ZNF 543。我们通过逻辑回归和k倍交叉验证验证了这10个基因。我们还在一个独立的数据集中验证了关键基因，发现AD和健康对照组之间的GPR174、TRAF1、ROD1、RAET1E、OR4K2、MRPL23、ARMCX5和EDN3存在显著差异。此外，在5XFAD转基因小鼠中，Wnt7b、Gpr174、Ptbp3、Mrp123、Armcx5和Raet1e的差异表达趋势与它们在独立数据集中的差异表达趋势一致。本研究结果为AD患者提供了潜在的治疗靶点。
Alzheimer's disease (AD) is an age-related neurodegenerative disorder characterized by cognitive impairment and memory loss, for which there is no effective cure to date. In the past several years, numerous studies have shown that increased inflammation in AD is a major cause of cognitive impairment. This study aimed to reveal 22 kinds of peripheral immune cell types and key genes associated with AD. The prefrontal cortex transcriptomic data from Gene Expression Omnibus (GEO) database were collected, and CIBERSORT was used to assess the composition of 22 kinds of immune cells in all samples. Weighted gene co-expression network analysis (WGCNA) was used to construct gene co-expression networks and identified candidate module genes associated with AD. The least absolute shrinkage and selection operator (LASSO) and random forest (RF) models were constructed to analyze candidate module genes, which were selected from the result of WGCNA. The results showed that the immune infiltration in the prefrontal cortex of AD patients was different from healthy samples. Of all 22 kinds of immune cells, M1 macrophages were the most relevant cell type to AD. We revealed 10 key genes associated with AD and M1 macrophages by LASSO and RF analysis, including ARMCX5, EDN3, GPR174, MRPL23, RAET1E, ROD1, TRAF1, WNT7B, OR4K2 and ZNF543. We verified these 10 genes by logistic regression and k-fold cross-validation. We also validated the key genes in an independent dataset, and found GPR174, TRAF1, ROD1, RAET1E, OR4K2, MRPL23, ARMCX5 and EDN3 were significantly different between the AD and healthy controls. Moreover, in the 5XFAD transgenic mice, the differential expression trends of Wnt7b, Gpr174, Ptbp3, Mrpl23, Armcx5 and Raet1e are consistent with them in independent dataset. Our results provided potential therapeutic targets for AD patients.
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影响因子：
25
作者：
Habib, Naomi;McCabe, Cristin;Medina, Sedi;Varshavsky, Miriam;Kitsberg, Daniel;Dvir-Szternfeld, Raz;Green, Gilad;Dionne, Danielle;Nguyen, Lan;Marshall, Jamie L.;Chen, Fei;Zhang, Feng;Kaplan, Tommy;Regev, Aviv;Schwartz, Michal
通讯作者：
Schwartz, Michal
WGCNA：用于加权相关网络分析的 R 包。
影响因子：
3
作者：
Langfelder P;Horvath S
通讯作者：
Horvath S
影响因子：
48
作者：
Kalaria, Raj N.;Maestre, Gladys E.;Arizaga, Raul;Friedland, Robert P.;Galasko, Doug;Hall, Kathleen;Luchsinger, Jose A.;Ogunniyi, Adesola;Perry, Elaine K.;Potocnik, Felix;Prince, Martin;Stewart, Robert;Wimo, Anders;Zhang, Zhen-Xin;Antuono, Piero
通讯作者：
Antuono, Piero
影响因子：
64.5
作者：
Keren-Shaul, Hadas;Spinrad, Amit;Amit, Ido
通讯作者：
Amit, Ido
DOI：
10.1083/jcb.201709069
发表时间：
2018-02-05
期刊：
The Journal of cell biology
影响因子：
--
作者：
Hansen DV;Hanson JE;Sheng M
通讯作者：
Sheng M