Tracing the cell-type-specific modules of immune responses during COVID-19 progression using scDisProcema

Abstract

COVID-19 has caused severe threats to lives and damage to property worldwide. The immunopathology of the disease is of particular concern. Currently, researchers have used gene co-expression networks (GCNs) to deepen the study of molecular mechanisms of immune responses to COVID-19. However, most efforts have not fully explored dynamic changes of cell-type-specific molecular networks in the disease process. This study proposes a GCN construction pipeline named single-cell Disease Progression cellular module analysis (scDisProcema), which can trace dynamic changes of immune system response during disease progression using single-cell data. Here, scDisProcema considers changes in cell fate and expression patterns during disease development, identifying gene modules responsible for different immune cells. The hub genes are screened for each module by the specific expression level and the intercellular connectivity of modules. Based on functional items enriched by each gene module, we elucidate the biological processes of different cells involved in disease development and explain the molecular mechanisms underlying the process of cell depletion or proliferation caused by disease. Compared with traditional WGCNA methods, scDisProcema can make more convenient use of the heterogeneity information provided by scRNA-seq data and has great potential in exploring molecular changes during disease progression and organ development.