Integration of Genetic and Immune Infiltration Insights into Data Mining of Multiple Sclerosis Pathogenesis

Abstract

Background: Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system. MS pathogenesis is closely related to the environment, genetic, and immune system, but the underlying interactions have not been clearly elucidated. This study aims to unveil the genetic basis and immune landscape of MS pathogenesis with bioinformatics.Methods:Gene matrix wasretrieved from the gene expression database NCBI GEO. Then, bioinformatics was used to standardize the samples and obtain differentially expressed genes (DEGs). The protein-protein interaction network was constructed with DEGs on the STRING website. Cytohubbaplug-in and MCODE plug-in were used to mine hub genes. Meanwhile, the CIBERSORTX algorithm was used to explore the characteristics of immune cellinfiltration in MS brain tissues. Spearman correlation analysis was performed between genes and immune cells, and the correlation between genes and different types of brain tissues was also analyzed using the WGCNA method.Results:A total of 90 samples from 2 datasetswere included, and 882 DEGs and 10 hub genes closely related to MS were extracted. Functional enrichment analysis suggested the roleof immune response in MS. Besides,CIBERSORTX algorithm results showed that MS brain tissuescontained a variety of infiltrating immune cells. Correlation analysis suggested that the hub genes were highly relevant to chronic active white matter lesions.Certain hub genes played a role in the activation of immune cells such as macrophages and natural killer cells.Conclusions: Our study shall provideguidance for the further study of the genetic basis and immune infiltration mechanism of MS.

Integration of Genetic and Immune Infiltration Insights into Data Mining of Multiple Sclerosis Pathogenesis

“…Permanent myeloid cells can be found in all tissues and organs. In the case of infection or tissue injury, monocytes or granulocytes (especially neutrophils) can be recruited from the circulation to participate in the promotion of inflammatory response at the beginning and play the roles in tissue repair and regeneration at the later stage [ 46 , 47 ]. The previous study on immune cell patterns of gene expression has suggested that the development of MS is caused by a wide subset of cells [ 42 ].…”