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. 2018 May 5;217(11):1690-1698.
doi: 10.1093/infdis/jiy086.

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

Iryna Nikolayeva  1 , Pierre Bost  1   2 , Isabelle Casademont  3   4 , Veasna Duong  5 , Fanny Koeth  3   4 , Matthieu Prot  3   4 , Urszula Czerwinska  6 , Sowath Ly  5 , Kevin Bleakley  7   8 , Tineke Cantaert  9 , Philippe Dussart  5 , Philippe Buchy  5   10 , Etienne Simon-Lorière  3   4 , Anavaj Sakuntabhai  3   4 , Benno Schwikowski  1
Affiliations

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

Iryna Nikolayeva et al. J Infect Dis. .

Abstract

Background: 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.

Methods: 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.

Results: 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 the PBMCs and whole blood datasets, respectively.

Conclusions: The signature could detect severe dengue in secondary-infected patients upon hospital admission. Its genes offer new insights into the pathogenesis of severe dengue.

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Figures

Figure 1.
Figure 1.
Discovery and validation of the severe dengue signature.
Figure 2.
Figure 2.
Evaluation of classification performance. A, Cross-validated training data, various methods. B, Validation data, our signature.
Figure 3.
Figure 3.
Visual representation of the RNA signature.
See this image and copyright information in PMC

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