Abstract
Septic shock is a major medical problem with high morbidity and mortality and incompletely understood biology. Integration of multiple data sets into a single analysis framework empowers discovery of new knowledge about the condition that may have been missed by individual analysis of each of these datasets. Electronic search was performed on medical literature and gene expression databases for selection of transcriptomic studies done in circulating leukocytes from human subjects suffering from septic shock. Gene-level meta-analysis was conducted on the six selected studies to identify the genes consistently differentially expressed in septic shock. This was followed by pathway-level analysis using three different algorithms (ORA, GSEA, SPIA). The identified up-regulated pathway, Osteoclast differentiation pathway (hsa04380) was validated in two independent cohorts. Of the pathway, 25 key genes were selected that serve as an expression signature of Septic Shock.
Highlights
Septic shock (SS) is a serious medical condition that claims many lives every year worldwide
Normalized gene expression data of the studies were retrieved from Gene Expression Omnibus (GEO) and analyzed to detect differentially expressed genes (Fig 2)
SS was compared with control and the six p-values were combined to generate a single p-value per gene
Summary
Septic shock (SS) is a serious medical condition that claims many lives every year worldwide. 2% of the patients admitted to the hospital are diagnosed with SS [1], with mortality of 40–60% within 30 days [2]. Of these patients, half are treated in the intensive care unit (ICU), representing 10% of all ICU admissions [2, 3]. The number of cases in USA exceeds 750,000 per year [2], and has been estimated up to 19 million cases worldwide per year [4]. With a number of unsuccessful clinical trials, there is urgent need for new directions in research [5]
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