Abstract

A Novel Blood-based, Host Response Gene Expression Signature for Early Sepsis

Siew Hwa Ong, CEO, Acumen Research Laboratories

Sepsis is a life-threatening organ dysfunction caused by dysregulated host responses to infection. Signs and symptoms of early-stage sepsis are non-specific, making early identification challenging and posing risks of delayed treatment, longer hospitalization periods and higher mortality. In a prospective study involving 300 subjects, a panel of 19 sepsis-regulated genes was derived and clinically validated. A diagnostic algorithm was developed for analysis of the qRT-PCR gene expression data of the sepsis gene panel, giving aggregated numerical scores to stratify patients who have infection or infection with risks of sepsis (ie. identification of early sepsis), among all suspect cases. Clinical validation was achieved by a follow up study with an independent cohort (n=170), the gene panel achieved an accuracy of 97.65% (98.63% sensitivity, 91.67% specificity) for detecting infection; and an accuracy of 80.59% (82.11% sensitivity, 76.60% specificity) for identification of early sepsis. Direct comparison with Procalcitonin (n=267) showed highly superior diagnostic accuracy of early sepsis by our gene panel. Conclusion: our novel 19-gene sepsis panel and data analysis algorithm reliably detected the presence of infection and early sepsis among patients, providing strong proof-of-concept data for the development of a clinically viable molecular diagnostic test for sepsis.