基于单细胞测序生物信息学分析进行阿尔茨海默病生物标志物的发掘

Discovery of Alzheimer’s Disease Biomarkers Based on Single-Cell Sequencing Bioinformatics Analysis

摘要: 目的：阿尔茨海默病(Alzheimer’s Disease, AD)是一种常见的中枢神经系统退行性疾病，严重影响着我国以及全球老年人的生命健康，且近年来有年轻化趋势。然而，用于AD早期诊断的生物标志物仍然有待发掘，本研究旨在发掘可用于AD早期诊断的生物标志物，为AD早期诊治提供帮助；方法：本研究通过单细胞测序，鉴定出不同细胞亚群间的上下调基因及其表达量，将单细胞测序的结果通过加权基因共表达分析(WGCNA, Weighted Correlation Network Analysis)鉴定出与AD发病相关的关键基因群，并对这些基因类群进行GO (Gene Ontology)及KEGG (Kyoto Encyclopedia of Genes and Genomes)分析，得到其生物功能及通路，最后通过PPI (Protein-Protein Interaction Networks)蛋白互作网络构建及Cytoscape转换，将本研究结果可视化。此外，对模块基因利用CIBERSORT (Cell-type Identification by Estimating Relative Subsets of RNA Transcripts)进行免疫浸润分析，得到在AD中表达异常的免疫细胞；结果：1) 通过WGCNA及PPI蛋白互作网络构建得到三个关键基因，其有可能成为AD早期诊治的生物标志物。2) 通过CIBERSORT免疫浸润得到4种在AD中表达异常的免疫细胞。

Abstract: Objective: Alzheimer’s Disease (Alzheimer’s Disease, AD) is a common degenerative disease of the central nervous system, which seriously affects the life and health of the elderly in China and the world, and tends to be younger in recent years. However, biomarkers for early diagnosis of AD remain to be explored. The purpose of this study is to explore biomarkers that can be used for early diagnosis of AD and provide help for early diagnosis and treatment of AD. Method: In this study, the up-down genes and their expression levels among different cell subsets were identified by single-cell sequencing. The key gene groups related to AD pathogenesis were identified by WGCNA (Weighted Correlation Network Analysis), and their biological functions and pathways were analyzed by GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes). Finally, the results of this study were visualized by PPI (Protein-Protein Interaction Networks) protein interaction network construction and Cytoscape transformation. In addition, CIBERSORT (Cell-type Identification by Estimating Relative Subsets of RNA Transcripts) was used to immunize immune cells with abnormal expression in AD. Results: 1) Three key genes were obtained by WGCNA and PPI protein interaction network construction, which have the potential to be biomarkers for early diagnosis and treatment of AD. 2) Four kinds of immune cells with abnormal expression in AD were obtained by CIBERSORT immune infiltration.