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

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,...

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Autores principales: Gao, Wenliang, Kong, Wei, Wang, Shuaiqun, Wen, Gen, Yu, Yaling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9496783/
https://www.ncbi.nlm.nih.gov/pubmed/36138932
http://dx.doi.org/10.3390/brainsci12091196
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author Gao, Wenliang
Kong, Wei
Wang, Shuaiqun
Wen, Gen
Yu, Yaling
author_facet Gao, Wenliang
Kong, Wei
Wang, Shuaiqun
Wen, Gen
Yu, Yaling
author_sort Gao, Wenliang
collection PubMed
description 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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spelling pubmed-94967832022-09-23 Biomarker Genes Discovery of Alzheimer’s Disease by Multi-Omics-Based Gene Regulatory Network Construction of Microglia Gao, Wenliang Kong, Wei Wang, Shuaiqun Wen, Gen Yu, Yaling Brain Sci Article 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. MDPI 2022-09-05 /pmc/articles/PMC9496783/ /pubmed/36138932 http://dx.doi.org/10.3390/brainsci12091196 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gao, Wenliang
Kong, Wei
Wang, Shuaiqun
Wen, Gen
Yu, Yaling
Biomarker Genes Discovery of Alzheimer’s Disease by Multi-Omics-Based Gene Regulatory Network Construction of Microglia
title Biomarker Genes Discovery of Alzheimer’s Disease by Multi-Omics-Based Gene Regulatory Network Construction of Microglia
title_full Biomarker Genes Discovery of Alzheimer’s Disease by Multi-Omics-Based Gene Regulatory Network Construction of Microglia
title_fullStr Biomarker Genes Discovery of Alzheimer’s Disease by Multi-Omics-Based Gene Regulatory Network Construction of Microglia
title_full_unstemmed Biomarker Genes Discovery of Alzheimer’s Disease by Multi-Omics-Based Gene Regulatory Network Construction of Microglia
title_short Biomarker Genes Discovery of Alzheimer’s Disease by Multi-Omics-Based Gene Regulatory Network Construction of Microglia
title_sort biomarker genes discovery of alzheimer’s disease by multi-omics-based gene regulatory network construction of microglia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9496783/
https://www.ncbi.nlm.nih.gov/pubmed/36138932
http://dx.doi.org/10.3390/brainsci12091196
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