Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Genome-wide gene expression analysis of human whole-blood samples in in response to dengue disease

ABSTRACT: We looked at the whole-blood transcriptional profiling on dengue patients sampled within 72h of fever presentation and compared the signatures with autologous samples drawn at defervescence and convalescence and to control patients with fever of other etiology. Our data show that the early response in patients mimics those previously only described in vitro and suggests that this innate immune responses may initiate the later adaptive immune responses. Total RNA obtained from whole-blood of dengue patients with fever presentation, defervescence and convalescence are compared. Also, dengue patients with fever presentation are compared with control patients which are with fever of other etiology. 119 samples are analysed, which include 31 dengue patients and 26 control patients.

ORGANISM(S): Homo sapiens

SUBMITTER: ling ling

PROVIDER: E-GEOD-28405 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description: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 and 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) and 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 The samples correspond to blood samples from 26 patients from a cohort in Brazil, divided into three classes, DHF, DF, ND, as follows: 18 were confirmed dengue 3, genotype III cases, among which 10 were diagnosed as dengue hemorrhagic fever (DHF) and 8 as classical dengue fever (DF), and 8 control samples (ND) from febrile patients confirmed to be not infected with dengue. None of the DHF patients presented vasculopathy signs and symptoms at the time the samples used in the functional genomic characterization were collected. At the time of collection the patients referred approximately 5 days of disease and the absence of fever was reported two to three days after enrollment. The samples from the DF, DHF and ND patients were matched to avoid significant differences regarding patient age, gender, dengue infection history and days of symptoms among the groups.

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Genome-wide gene expression analysis of human whole-blood samples in in response to dengue disease

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