Mortality prediction in sepsis via gene expression analysis: a community approach

Abstract

Improved risk stratification and prognosis in sepsis is a critical unmet need. Clinical severity scores and available assays such as blood lactate reflect global illness severity with suboptimal performance, and do not specifically reveal the underlying dysregulation of sepsis. Here three scientific groups were invited to independently generate prognostic models for 30-day mortality using 12 discovery cohorts (N=650) containing transcriptomic data collected from primarily community-onset sepsis patients. Predictive performance was validated in 5 cohorts of community-onset sepsis patients (N=189) in which the models showed summary AUROCs ranging from 0.765-0.89. Similar performance was observed in 4 cohorts of hospital-acquired sepsis (N=282). Combining the new gene-expression-based prognostic models with prior clinical severity scores led to significant improvement in prediction of 30-day mortality (p<0.01). These models provide an opportunity to develop molecular bedside tests that may improve risk stratification and mortality prediction in patients with sepsis, improving both resource allocation and prognostic enrichment in clinical trials.

A Novel 29-Messenger RNA Host-Response Assay From Whole Blood Accurately Identifies Bacterial and Viral Infections in Patients Presenting to the Emergency Department With Suspected Infections: A Prospective Observational Study*

“…The Inflammatix Bacterial Viral Non-Infected version 2 (IMX-BVN-2) classifier evaluated here (to be launched under the name InSep; Inflammatix, Burlingame, CA) is a new host-response assay and neural network-based classifier, which has the potential to meet these needs. The assay measures 29 host mRNAs from peripheral blood and incorporates advanced machine learning to calculate three scores for predicting: 1) the likelihood of bacterial infection, 2) the likelihood of viral infection, and 3) the risk for 30-day mortality (4,(6)(7)(8)(9). In this study, we investigate its accuracy for predicting the presence of bacterial and viral infections in a final cohort of 312 prospectively enrolled patients in the ED with clinically suspected acute infections and/or sepsis with at least one vital sign change.…”

Pediatric Sepsis Endotypes Among Adults With Sepsis

“…These data from the GAinS study represent adults with sepsis used in the discovery and validation of the SRS groupings taken from the earliest available time point after enrollment [1, 2]. Since the two cohorts were from the same study and represent the same clinical circumstances, we used ComBat normalization [8, 9] to co-normalize the cohorts into a single dataset representing 549 unique cases with SRS assignments. From this dataset, we extracted expression data for the 100 endotyping genes.…”

Intensive care medicine in 2050: precision medicine

“…Similar efforts were developed for children with sepsis, but based on panel of protein biomarkers [5, 6]. The most recent effort in this area involved a multi-research group collaboration that leveraged publically available transcriptomic data to develop and validate prognostic models for patients with sepsis [7]. …”