Biomarker Genes Discovery of Alzheimer's Disease by Multi-Omics-Based Gene Regulatory Network Construction of Microglia

被引:3
作者
Gao, Wenliang [1 ]
Kong, Wei [1 ]
Wang, Shuaiqun [1 ]
Wen, Gen [2 ]
Yu, Yaling [2 ,3 ]
机构
[1] Shanghai Maritime Univ, Coll Informat Engn, 1550 Haigang Ave, Shanghai 201306, Peoples R China
[2] Shanghai Jiao Tong Univ Affiliated Peoples Hosp 6, Dept Orthoped Surg, Shanghai 200233, Peoples R China
[3] Shanghai Jiao Tong Univ Affiliated Peoples Hosp 6, Inst Microsurg Extrem, Shanghai 200233, Peoples R China
基金
中国国家自然科学基金; 上海市自然科学基金;
关键词
SCENIC; multi-omics; gene regulatory network; microglia; prognosis; immunotherapy; BETA;
D O I
10.3390/brainsci12091196
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Microglia, the major immune cells in the brain, mediate neuroinflammation, increased oxidative stress, and impaired neurotransmission in Alzheimer's disease (AD), in which most AD risk genes are highly expressed. In microglia, due to the limitations of current single-omics data analysis, risk genes, the regulatory mechanisms, the mechanisms of action of immune responses and the exploration of drug targets for AD immunotherapy are still unclear. Therefore, we proposed a method to integrate multi-omics data based on the construction of gene regulatory networks (GRN), by combining weighted gene co-expression network analysis (WGCNA) with single-cell regulatory network inference and clustering (SCENIC). This enables snRNA-seq data and bulkRNA-seq data to obtain data on the deeper intermolecular regulatory relationships, related genes, and the molecular mechanisms of immune-cell action. In our approach, not only were central transcription factors (TF) STAT3, CEBPB, SPI1, and regulatory mechanisms identified more accurately than with single-omics but also immunotherapy targeting central TFs to drugs was found to be significantly different between patients. Thus, in addition to providing new insights into the potential regulatory mechanisms and pathogenic genes of AD microglia, this approach can assist clinicians in making the most rational treatment plans for patients with different risks; it also has significant implications for identifying AD immunotherapy targets and targeting microglia-associated immune drugs.
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页数:19
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