Unraveling the role of histone acetylation in sepsis biomarker discovery.

INTRODUCTION

Sepsis is a life-threatening condition caused by a dysregulated immune response to infection. Despite advances in clinical care, effective biomarkers for early diagnosis and prognosis remain lacking. Emerging evidence suggests that histone acetylation plays a crucial role in the pathophysiology of sepsis.

METHODS

Transcriptomic and single-cell RNA sequencing data were used to identify histone acetylation-related genes. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were performed, followed by machine learning algorithms (LASSO, SVM-RFE, and Boruta) to screen for potential biomarkers. Mendelian randomization (MR), RT-qPCR, and functional assays were conducted for validation.

RESULTS

, , and were identified as key biomarkers. A predictive nomogram demonstrated strong diagnostic potential. Immune infiltration and single-cell analyses linked the biomarkers to macrophage activity. MR analysis confirmed as a causal factor in sepsis. Functional assays showed that knockdown of suppressed and expression, indicating its pro-inflammatory role.

DISCUSSION

This study identifies novel biomarkers associated with histone acetylation and immune dysregulation in sepsis. These findings deepen our understanding of sepsis pathogenesis and may facilitate the development of improved diagnostic and therapeutic strategies.