Discovery of potential gene biomarkers may provide effective septic shock diagnosis, treatment, and prognosis. Using functional gene-set enrichment analysis, we validated the known septic shock-related genes, pathways and functional groups, and identified the unexplored septic shock-related genes and functional groups.
Furthermore, these approaches can augment parallel efforts using clinical markers for earlier identification of sepsis and septic shock, providing meaningful input at the point of care 20, 21, 22. The gene expression profiles discovered by this statistical approach may lead to new insights that support sucessful prognosis, especially among patients with poor long term outcomes 19. To that end, gene expression data from 181 samples collected from critically ill patients admitted to the pediatric intensive care unit (PICU) within the first 24 hours of their admission, were analyzed using multiple statistical testing methods to identify gene biomarkers. The purpose of this study is to identify differentially expressed pediatric septic shock biomarkers using gene expression data to predict long-term outcomes.
Statistical testing and machine learning methods have been frequently used to successfully utilize omics data for biomarker discovery 2, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18. High-throughput technologies support the analysis of gene expressions and also enable the ability to determined activity of these genes in different conditions 8. Furthermore, it has been demonstrated that multiple genes and immune system-related pathways participate in development of pediatric septic shock 7. Many strategies for uncovering biomarkers exist, such as mass-spectrometry, protein arrays, and gene-expression profiling. Single or combination biomarkers are increasingly being analyzed and tested in the context of genes, RNA, or proteins 3, 4, 5, 6.
Multi-omics sequencing technologies have increased the number of genetic biomarkers 2. Septic shock is a life-threatening organ dysfunction caused by an imbalanced host response to infection 1. The identification of the septic shock gene biomarkers may facilitate in septic shock diagnosis, treatment, and prognosis. Differential gene expression analysis revealed the genes involved in the immune response, chemokine-mediated signaling, neutrophil chemotaxis, and chemokine activity and distinguished the septic shock survivor from non-survivor. Using functional enrichment analysis of differentially expressed genes, we validated the known genes and pathways in septic shock and identified the unexplored septic shock-related genes and functional groups. The gene expression signatures showed discriminatory power between pediatric septic shock survivors and nonsurvivor types. We identified 53 differentially expressed pediatric septic shock biomarkers using gene expression data sampled from 181 patients admitted to the pediatric intensive care unit within the first 24 hours of their admission. Multiple genetic markers and functional pathways play a part in development and progression of pediatric septic shock. Advancements in high-throughput sequencing techniques have increased the number of potential genetic biomarkers under review. Septic shock is a devastating health condition caused by uncontrolled sepsis.