Characteristics And Functions Of Sepsis Diagnostic Biomarkers:A Network Structure-based Study

Sepsis,characterized by rapid onset and high mortality,has difficulties in early diagnosis due to the complexity of the pathogenesis.Therefore,studies on the characteristics and functions of sepsis diagnostic biomarkers(SDBs)are of great importance.In this study,the subjects were divided into two categories: adults and neonates,and the SDBs related to them were manually collected.Gene expression data of sepsis patients and healthy controls were used for differential expression analysis.Adult and neonatal sepsis-specific networks were constructed respectively based on the integration of proteinprotein interaction network and gene expression data.Then the positional relationship between SDBs and differentially expressed(DE)genes,as well as the network topological characteristics of SDBs were deeply analyzed.GO analysis,IPA diseases and functions annotation,pathway enrichment analysis and biological function classification were performed for the systematic investigation of SDBs functions.This study identified 46 adult SDBs and 45 neonatal SDBs,most of which were cytokine/chemokine biomarkers.Among them,13 biomarkers were shared by adult and neonatal group.27% of adult SDBs and 54% of neonatal SDBs were significantly DE in sepsis(p-value<0.05).In the sepsis-specific networks,52% of adult SDBs and 53% of neonatal SDBs were the first neighbor of DE genes.The topological characteristics of SDBs in sepsis-specific network included: adult SDBs were significantly located on the node with degree that secondary to Hub and low closeness(p-value<0.05);neonatal SDBs were significantly located on the node with degree that secondary to Hub,low closeness and low vulnerability(p-value<0.05).According to the literature analysis,the KEGG and IPA pathways enriched by adult SDBs and neonatal SDBs were associated with sepsis,and the differences remain to be further in-depth studied.This study systematically explored the characteristics and biological functions of adult SDBs and neonatal SDBs at the network level.The conclusions are valuable for the discovery and clinical transformation of SDBs,which have certain theoretical value and practical significance.