Genome-wide expression profiling deciphers host responses altered during dengue shock syndrome and reveals the role of innate immunity in severe dengue.

PloS One
Stéphanie DevignotPatricia Couissinier-Paris

Abstract

Deciphering host responses contributing to dengue shock syndrome (DSS), the life-threatening form of acute viral dengue infections, is required to improve both the differential prognosis and the treatments provided to DSS patients, a challenge for clinicians. Based on a prospective study, we analyzed the genome-wide expression profiles of whole blood cells from 48 matched Cambodian children: 19 progressed to DSS while 16 and 13 presented respectively classical dengue fever (DF) or dengue hemorrhagic fever grades I/II (DHF). Using multi-way analysis of variance (ANOVA) and adjustment of p-values to control the False Discovery Rate (FDR<10%), we identified a signature of 2959 genes differentiating DSS patients from both DF and DHF, and showed a strong association of this DSS-gene signature with the dengue disease phenotype. Using a combined approach to analyse the molecular patterns associated with the DSS-gene signature, we provide an integrative overview of the transcriptional responses altered in DSS children. In particular, we show that the transcriptome of DSS children blood cells is characterized by a decreased abundance of transcripts related to T and NK lymphocyte responses and by an increased abundance of anti-inflammato...Continue Reading

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Datasets Mentioned

BETA
GSE17924

Methods Mentioned

BETA
ELISA
Feature Extraction
PCR

Software Mentioned

TIGR MeV ( MultiExperiment Viewer )
SAM ( Significant Analysis of Microarray )
Cluster
Feature Extraction
Limma
Tree View
GeneANOVA
Ingenuity Pathway Analysis software ( IPA
IPA

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