Identification of pericyte loss and neutrophils infiltration in Focal cortical dysplasia by Integrated Analysis of Single-Cell and Bulk RNA-Sequencing

Abstract

Introduction Epilepsy is one of the most common serious brain conditions. Focal cortical dysplasia(FCD) is the most common diagnosis in children among patients with drug-resistant epilepsy who require surgical treatment. However, the pathogenic genes and the interaction between different cells of FCD are not clear, especially the immune mechanism of FCD remains nascent. We further analyze FCD data in terms of genes, cellular changes and immune infiltration by integrating bulk and single-cell sequencing data. Methods The scRNA-seq dataset GSE201048 and bulk RNA-seq dataset GSE62019 were combined to perform deconvolution to infer the cell composition ratio of samples in bulk RNA-seq of FCD. We used AUCell analysis, GO and KEGG enrichment analysis, cell communication analysis and WGCNA to analyze pericyte function and pericyte cell communication. PPI was used to identify hub genes. GSVA and The Pearson correlation analysis were used to identify relationships between hub genes and pericyte. We used logistic regression to construct a diagnostic model based on hub genes. Finally, we performed immune infiltration analysis. Results Pericytes were significantly reduced in FCD. Neutrophils cells were significantly different between the FCD group and the control group ( p < 0.05 ), and the degree of immune infiltration was higher in the FCD group. PPI network analysis identified 5 hub genes related to pericytes. Through LASSO regression analysis, we established a risk score model containing five genes. Conclusion This study provides a new perspective to study the molecular mechanism and cell changes in FCD. It was found for the first time that pericytes play an important role in FCD.