Bulk RNA Sequencing With Integrated Single-Cell RNA Sequencing Identifies BCL2A1 as a Potential Diagnostic and Prognostic Biomarker for Sepsis

Front Public Health. 2022 Jun 27;10:937303. doi: 10.3389/fpubh.2022.937303. eCollection 2022.


Background: Sepsis is one of the leading causes of morbidity and mortality worldwide in the intensive care unit (ICU). The prognosis of the disease strongly depends on rapid diagnosis and appropriate treatment. Thus, some new and accurate sepsis-related biomarkers are pressing needed and their efficiency should be carefully demonstrated.

Methods: Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were applied to detect sepsis and monocyte/macrophage-related genes. Least absolute shrinkage and selection operator (LASSO) and random forest regression analyses were used in combination to screen out prognostic genes. Single-cell RNA sequence profiling was utilized to further verify the expression of these genes on a single cell level. Receiver operating characteristic (ROC) curve and decision curve analysis (DCA) were also applied to verify the diagnostic value of the target biomarkers.

Results: The intersections of the genes detected by differential expression and WGCNA analyses identified 141 overlapping candidate genes that were closely related to sepsis and macrophages. The LASSO and random forest regression analyses further screened out 17 prognostic genes. Single-cell RNA sequencing analysis detected that FCGR1A and BCL2A1 might be potential biomarkers for sepsis diagnosis and the diagnostic efficacy of BCL2A1 was further validated by ROC curve and DCA.

Conclusions: It was revealed that BCL2A1 had good diagnostic and prognostic value for sepsis, and that it can be applied as a potential and novel biomarker for the management of the disease.

Keywords: biomarker; diagnosis; sepsis; sequencing; single-cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Biomarkers / metabolism
  • Humans
  • Minor Histocompatibility Antigens* / metabolism
  • Prognosis
  • Proto-Oncogene Proteins c-bcl-2* / metabolism
  • Sepsis* / diagnosis
  • Sepsis* / genetics
  • Sepsis* / metabolism
  • Sequence Analysis, RNA


  • BCL2-related protein A1
  • Biomarkers
  • Minor Histocompatibility Antigens
  • Proto-Oncogene Proteins c-bcl-2