E-MTAB-3162 - Time since Onset of Disease and Individual Clinical Markers Associate with Transcriptional Changes in Uncomplicated Dengue
Submitted on 30 April 2012, last updated on 10 December 2014, released on 28 February 2015
Background 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. Methodology/principle findings 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 and coagulation. Overall, we see a shift in the transcriptome from immunity and inflammation to repair and recovery during the course of DENV infection. Conclusions/significance Time since onset of disease associates with the shift in transcriptome signatures from immunity and inflammation to cell cycle and repair mechanisms in patients with non-severe dengue. The strong association of time with blood transcriptome changes hampers both the discovery as well as the potential application of biomarkers in dengue. However, we identified gene expression modules that associate with key clinical parameters of dengue that reflect the systemic activity of disease during the course of infection. The expression level of these gene modules may support earlier detection of disease progression as well as clinical management of dengue.
transcription profiling by array, observational design, time series design
Time since onset of disease and individual clinical markers associate with transcriptional changes in uncomplicated dengue. van de Weg CA, van den Ham HJ, Bijl MA, Anfasa F, Zaaraoui-Boutahar F, Dewi BE, Nainggolan L, van IJcken WF, Osterhaus AD, Martina BE, van Gorp EC, Andeweg AC. :e0003522 (2015), PMID:25768297