A Blood RNA Signature Detecting Severe Disease in Young Dengue Patients at Hospital Arrival

The Journal of Infectious Diseases
Iryna NikolayevaBenno Schwikowski

Abstract

Early detection of severe dengue can improve patient care and survival. To date, no reliable single-gene biomarker exists. We hypothesized that robust multigene signatures exist. We performed a prospective study on Cambodian dengue patients aged 4 to 22 years. Peripheral blood mononuclear cells (PBMCs) were obtained at hospital admission. We analyzed 42 transcriptomic profiles of patients with secondary dengue infected with dengue serotype 1. Our novel signature discovery approach controls the number of included genes and captures nonlinear relationships between transcript concentrations and severity. We evaluated the signature on secondary cases infected with different serotypes using 2 datasets: 22 PBMC samples from additional patients in our cohort and 32 whole blood samples from an independent cohort. We identified an 18-gene signature for detecting severe dengue in patients with secondary infection upon hospital admission with a sensitivity of 0.93 (95% confidence interval [CI], .82-.98), specificity of 0.67 (95% CI, .53-.80), and area under the receiver operating characteristic curve (AUC) of 0.86 (95% CI, .75-.97). At validation, the signature had empirical AUCs of 0.85 (95% CI, .69-1.00) and 0.83 (95% CI, .68-.98) for t...Continue Reading

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Citations

Sep 15, 2018·Pathogens and Global Health·Sandra BosPhilippe Despres
Dec 12, 2018·Proceedings of the National Academy of Sciences of the United States of America·Fabio ZaniniShirit Einav
Sep 12, 2018·Toxins·Camila Dias-LopesLiza Felicori
Feb 15, 2021·Molecular & Cellular Proteomics : MCP·Kristina AllgoewerChristine Vogel
Jan 27, 2020·Trends in Microbiology·Makeda Robinson, Shirit Einav
Jul 21, 2020·Current Opinion in Virology·Abhay Ps RathoreAshley L St John

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