Meta-analysis reveals pathway signature of Septic Shock

Septic shock is a major medical problem with high morbidity and mortality and incompletely understood biology. Availability of genome-wide expression data from different studies on septic shock empowers the quest for hitherto unidentified pathways by integration and meta-analysis of multiple data sets. Electronic search was performed on medical literature and gene expression databases. Selection of studies was based on the organism (human subjects), tissue of origin (circulating leukocytes) and the platform technology (gene expression microarray). Gene-level meta-analysis was conducted on the six selected studies to identify the genes consistently differentially expressed in septic shock. These genes were then subjected to pathway analysis. The identified up-regulated pathway hsa 04380 (Osteoclast Differentiation) was validated in an independent cohort of patients. A simplified model was generated showing the major gene-modules dysregulated in SS.