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Gene expression profiling during early acute febrile stage of dengue infection can predict the disease outcome

Nascimento, EJM and Braga-Neto, U and Calzavara-Silva, CE and Gomes, ALV and Abath, FGC and Brito, CAA and Cordeiro, MT and Silva, AM and Magalhãnes, C and Andrade, R and Gil, LHVG and Marques, ETA (2009) Gene expression profiling during early acute febrile stage of dengue infection can predict the disease outcome. PLoS ONE, 4 (11).

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Background: We report the detailed development of biomarkers to predict the clinical outcome under dengue infection. Transcriptional signatures from purified peripheral blood mononuclear cells were derived from whole-genome gene-expression microarray data, validated by quantitative PCR and tested in independent samples. Methodology/Principal Findings: The study was performed on patients of a well-characterized dengue cohort from Recife, Brazil. The samples analyzed were collected prospectively from acute febrile dengue patients who evolved with different degrees of disease severity: classic dengue fever or dengue hemorrhagic fever (DHF) samples were compared with similar samples from other non-dengue febrile illnesses. The DHF samples were collected 2-3 days before the presentation of the plasma leakage symptoms. Differentially-expressed genes were selected by univariate statistical tests as well as multivariate classification techniques. The results showed that at early stages of dengue infection, the genes involved in effector mechanisms of innate immune response presented a weaker activation on patients who later developed hemorrhagic fever, whereas the genes involved in apoptosis were expressed in higher levels. Conclusions/Significance: Some of the gene expression signatures displayed estimated accuracy rates of more than 95%, indicating that expression profiling with these signatures may provide a useful means of DHF prognosis at early stages of infection. © 2009 Nascimento et al.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Nascimento, EJMejmn@pitt.eduEJMN
Braga-Neto, U
Calzavara-Silva, CE
Gomes, ALV
Abath, FGC
Brito, CAA
Cordeiro, MT
Silva, AM
Magalhãnes, C
Andrade, R
Marques, ETAmarques@pitt.eduMARQUES0000-0003-3826-9358
ContributionContributors NameEmailPitt UsernameORCID
Date: 19 November 2009
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 4
Number: 11
DOI or Unique Handle: 10.1371/journal.pone.0007892
Schools and Programs: School of Public Health > Infectious Diseases and Microbiology
Refereed: Yes
MeSH Headings: Adult; Aged; Aged, 80 and over; Apoptosis; Biological Markers--metabolism; Brazil; Cohort Studies; Dengue--diagnosis; Dengue--genetics; Dengue--metabolism; Dengue Virus--genetics; Dengue Virus--metabolism; Female; Fever--diagnosis; Fever--metabolism; Gene Expression Regulation; Humans; Male; Middle Aged; Multivariate Analysis; Oligonucleotide Array Sequence Analysis; Treatment Outcome
Other ID: NLM PMC2775946
PubMed Central ID: PMC2775946
PubMed ID: 19936257
Date Deposited: 03 Aug 2012 16:31
Last Modified: 09 Apr 2019 16:55


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