Posted in Dengue, Resource

A 20-Gene Set Predictive of Progression to Severe Dengue

Methodology employed by Robinson et al., Cell Reports, 2019. The 20-gene set was used to distinguish between individuals with severe and mild dengue

The gene signatures predictive of severe dengue disease progression is poorly understood.

The study by Robinson et al., utilise 10 publicly available datasets and divided them into 7 “discovery” and 3 “validation” datasets. In the discovery datasets, a total of 59 differentially expressed genes (FDR < 10%, effect size > 1.3-fold) was detected between patients who progress to DHF and/or DSS (DHF/DSS) versus patients with an uncomplicated course (dengue fever).

An iterative greedy forward search to the 59 genes revealed a final set of and 20 differentially expressed genes (3 over-expressed, 17 under-expressed) in DHF/DSS (Gene list as shown in figure above). A dengue score for each sample was obtained by subtracting the geometric mean expression of the 17 under-expressed genes from the geometric mean expression of the 3 over-expressed genes.

The 20-gene dengue severity scores distinguished DHF/DSS from dengue fever upon presentation and prior to the onset of severe complications with a summary area under the curve (AUC) = 0.79 in the discovery datasets. The 20-gene dengue scores also accurately identified dengue patients who will develop DHF/DSS in all three validation datasets.

To further validate this signature, the authors tested a cohort of prospectively enrolled dengue patients in Colombia. The 20-gene dengue score, measured by qPCR, distinguished severe dengue from dengue with or without warning signs (AUC = 0.89) and even severe dengue from dengue with warning signs (AUC = 0.85).

Finally, the 20-gene set is significantly downregulated in natural killer (NK) and NK T (NKT) cells, indicating the role of NK and NKT cells in modulating severe disease outcome.

Dataset deposited under Gene Expression Omnibus (GEO): GSE124046

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