Abstract
BackgroundThe host response to bacterial sepsis is reported to be nonspecific regardless of the causative pathogen. However, newer paradigms indicated that the host response of Gram-negative sepsis may be different from Gram-positive sepsis, and the difference has not been clearly clarified. The current study aimed to explore the difference by identifying the differential gene sets using the genome-wide technique.MethodsThe training dataset GSE6535 and the validation dataset GSE13015 were used for bioinformatics analysis. The distinct gene sets of sepsis with different infections were screened using gene set variation analysis (GSVA) and gene set enrichment analysis (GSEA). The intersection gene sets based on the two algorithms were confirmed through Venn analysis. Finally, the common gene sets between GSE6535 and GSE13015 were determined by GSEA.ResultsTwo immunological gene sets in GSE6535 were identified based on GSVA, which could be used to discriminate sepsis caused by Gram-positive, Gram-negative, or mixed infection. A total of 19 gene sets were obtained in GSE6535 through Venn analysis based on GSVA and GSEA, which revealed the heterogeneity of Gram-negative and Gram-positive sepsis at the molecular level. The result was also verified by analysis of the validation set GSE13015, and 40 common differential gene sets were identified between dataset GSE13015 and dataset GSE6535 by GSEA.ConclusionsThe identified differential gene sets indicated that host response may differ dramatically depending on the inciting organism. The findings offer new insight to investigate the pathophysiology of bacterial sepsis.
Highlights
Sepsis is a potentially life-threatening condition caused mainly by bacterial infection, with high morbidity and mortality
Organs damaged by Gram-positive sepsis are clinically no different from Gram-negative sepsis, there is increasing evidence that differences exist in the host response (Li et al, 2017)
The heatmap showed that the enrichment score (ES) patterns may distinguish Gram-positive sepsis patients from Gram-negative sepsis patients (Figure 3A)
Summary
Sepsis is a potentially life-threatening condition caused mainly by bacterial infection, with high morbidity and mortality. It is defined as infection accompanied by organ dysfunction resulting from dysregulated host responses (Singer et al, 2016). Organs damaged by Gram-positive sepsis are clinically no different from Gram-negative sepsis, there is increasing evidence that differences exist in the host response (Li et al, 2017). Gram-positive bacteria require a highly orchestrated host response, with intracellular killing by neutrophils and macrophages. This is different for Gram-negative pathogens, which may be readily killed in the extracellular space by antibody and complement (Van Amersfoort et al, 2003). The current study aimed to explore the difference by identifying the differential gene sets using the genome-wide technique
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