Integrative Bioinformatics for Characterizing Atypical Memory B Cells Through scRNA-seq in COVID-19 скачать в хорошем качестве

Integrative Bioinformatics for Characterizing Atypical Memory B Cells Through scRNA-seq in COVID-19

2025 Immcantation Users Group Meeting https://immcantation.github.io/users-... Title: Integrative Bioinformatics for Characterizing Atypical Memory B Cells Through Single-Cell RNA-seq in COVID-19 Speaker: Dr. Melissa Garcia, Centro de Investigación en Alimentación y Desarrollo (CIAD) Abstract: Here we performed single-cell RNA sequencing of S1 and RBD protein-specific B cells from convalescent COVID-19 patients with different clinical manifestations. This study aimed to evaluate the role and developmental pathways of atypical memory B cells (MBCs) in response to SARS-CoV-2 infection. We employed bioinformatics tools to conduct multiple analyses, including the Immcantation framework particularly Change-O for VDJ alignment, clonal assignment, and germline reconstruction, along with SHazaM for analyzing somatic hypermutations as part of repertoire characterization. Additional analyses included differential gene expression, pathway enrichment, and trajectory analysis to further explore B cell responses. The results revealed a proinflammatory signature across B cell subsets associated with disease severity, as evidenced by the upregulation of genes such as GADD45B, MAP3K8, and NFKBIA critical and severe individuals. The repertoire analysis demonstrated variations in somatic hypermutation rates and gene usage between atypical and conventional MBCs. Furthermore, the analysis of atypical MBCs suggested a developmental pathway similar to that of conventional MBCs through germinal centers, as indicated by the expression of several genes involved in germinal center processes, including CXCR4, CXCR5,BCL2, and MYC. Additionally, the upregulation of genes characteristic of the immune response in COVID-19, such as ZFP36 and DUSP1, suggested that the differentiation and activation of atypical MBCs may be influenced by exposure to SARS-CoV-2 contributing to the immune response necessary for COVID-19 recovery. Our study contributes to a better understanding of atypical MBCs in COVID-19 and the role of other B cell subsets across different clinical manifestations.