Two gene set variation indexes as potential diagnostic tool for sepsis.

Abstract

Accurate diagnosis of sepsis remains challenging, new markers or combinations of markers are urgently needed. In the present study, we screened differentially expressed genes (DEGs) between sepsis and non-sepsis blood samples across three previously published gene expression data sets. Common upregulated and downregulated DEGs were ranked according to their average functional similarity. The ten genes (OLFM4, ORM1, CEP55, S100A12, S100P, LRG1, CEACAM8, MS4A4A, PLSCR1, and IL1R2) with the largest average functional similarity among the common upregulated genes and another ten genes (THEMIS, IL2RB, CD2, IL7R, CD3E, KLRB1, PVRIG, CCRR3, TGFBR3, and PLEKHA1) with the largest average functional similarity among the common downregulated genes were separately identified as the upregulated crucial gene set and the downregulated crucial gene set. Gene set variation analysis (GSVA) was used to obtain the GSVA index of each sample against the two crucial gene sets. Both the two crucial GSVA indexes may be robust markers for sepsis with high area under ROC curve. The diagnostic utility of the upregulated GSVA index was validated in another independent data set. Functional analyses revealed several sepsis-related pathways. In conclusion, we proposed two sepsis-related gene sets across multiple data sets and created two GSVA indexes with promising diagnostic value.