Genome-wide identification and functional analysis of dysregulated alternative splicing profiles in sepsis

Abstract

Background: An increasing body of evidence now shows that the long-term mortality of patients with sepsis are associated with various sepsis-related immune cell defects. Alternative splicing (AS), as a sepsis-related immune cell defect, is considered as a potential immunomodulatory therapy target to improve patient outcomes. However, our understanding of the role AS plays in sepsis is currently insufficient. Aim: This study investigated possible associations between AS and the gene regulatory networks affecting immune cells. We also investigated apoptosis and AS functionality in sepsis pathophysiology. Methods: In this study, we assessed publicly available mRNA-seq data that was obtained from the NCBI GEO dataset (GSE154918), which included a healthy group (HLTY), a mild infection group (INF1), asepsis group (Seps), and a septic shock group (Shock). A total of 79 samples (excluding significant outliers) were identified by a poly-A capture method to generate RNA-seq data. The variable splicing events and highly correlated RNA binding protein (RBP) genes in each group were then systematically analyzed. Results: For the first time, we used systematic RNA-seq analysis of sepsis-related AS and identified 1505 variable AS events that differed significantly (p