Time since onset of disease and individual clinical markers associate with transcriptional changes in uncomplicated dengue

PLoS Neglected Tropical Diseases
Cornelia A M van de WegArno C Andeweg

Abstract

Dengue virus (DENV) infection causes viral haemorrhagic fever that is characterized by extensive activation of the immune system. The aim of this study is to investigate the kinetics of the transcriptome signature changes during the course of disease and the association of genes in these signatures with clinical parameters. Sequential whole blood samples from DENV infected patients in Jakarta were profiled using affymetrix microarrays, which were analysed using principal component analysis, limma, gene set analysis, and weighted gene co-expression network analysis. We show that time since onset of disease, but not diagnosis, has a large impact on the blood transcriptome of patients with non-severe dengue. Clinical diagnosis (according to the WHO classification) does not associate with differential gene expression. Network analysis however, indicated that the clinical markers platelet count, fibrinogen, albumin, IV fluid distributed per day and liver enzymes SGOT and SGPT strongly correlate with gene modules that are enriched for genes involved in the immune response. Overall, we see a shift in the transcriptome from immunity and inflammation to repair and recovery during the course of a DENV infection. Time since onset of disea...Continue Reading

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Citations

Mar 5, 2016·Genome Biology·Shuzhen Sim, Martin L Hibberd
Jul 8, 2016·Science Translational Medicine·Timothy E SweeneyPurvesh Khatri
Sep 30, 2016·Critical Care Medicine·Timothy E Sweeney, Purvesh Khatri
Nov 30, 2019·Immunology·Alba GrifoniDaniela Weiskopf
Sep 19, 2018·BMC Bioinformatics·Weizhuang Zhou, Russ B Altman
Jan 27, 2020·Trends in Microbiology·Makeda Robinson, Shirit Einav

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Datasets Mentioned

BETA
E-MTAB-3162

Methods Mentioned

BETA
PCR
electrophoresis
chips
PCA

Software Mentioned

R
Bioconductor
Roast
Microarray Suite
Affymetrix
SGOT
GeneChip Operating Software
arrayExpress
Limma

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