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A host transcriptional signature for presymptomatic detection of infection in humans exposed to influenza H1N1 or H3N2.

dc.contributor.author Carin, Lawrence
dc.contributor.author Chen, M
dc.contributor.author Gilbert, AG
dc.contributor.author Ginsburg, Geoffrey Steven
dc.contributor.author Glickman, Seth W
dc.contributor.author Hero, Alfred
dc.contributor.author Huang, Y
dc.contributor.author Kingsmore, Stephen F
dc.contributor.author Lambkin-Williams, R
dc.contributor.author Lucas, Joseph E
dc.contributor.author McClain, MT
dc.contributor.author Nicholson, BP
dc.contributor.author Ramsburg, Elizabeth A
dc.contributor.author Varkey, J
dc.contributor.author Veldman, T
dc.contributor.author Woods, Christopher Wildrick
dc.contributor.author Zaas, Aimee Kirsch
dc.coverage.spatial United States
dc.date.accessioned 2014-07-22T16:09:16Z
dc.date.issued 2013
dc.identifier http://www.ncbi.nlm.nih.gov/pubmed/23326326
dc.identifier PONE-D-12-19352
dc.identifier.uri http://hdl.handle.net/10161/8944
dc.description.abstract There is great potential for host-based gene expression analysis to impact the early diagnosis of infectious diseases. In particular, the influenza pandemic of 2009 highlighted the challenges and limitations of traditional pathogen-based testing for suspected upper respiratory viral infection. We inoculated human volunteers with either influenza A (A/Brisbane/59/2007 (H1N1) or A/Wisconsin/67/2005 (H3N2)), and assayed the peripheral blood transcriptome every 8 hours for 7 days. Of 41 inoculated volunteers, 18 (44%) developed symptomatic infection. Using unbiased sparse latent factor regression analysis, we generated a gene signature (or factor) for symptomatic influenza capable of detecting 94% of infected cases. This gene signature is detectable as early as 29 hours post-exposure and achieves maximal accuracy on average 43 hours (p = 0.003, H1N1) and 38 hours (p-value = 0.005, H3N2) before peak clinical symptoms. In order to test the relevance of these findings in naturally acquired disease, a composite influenza A signature built from these challenge studies was applied to Emergency Department patients where it discriminates between swine-origin influenza A/H1N1 (2009) infected and non-infected individuals with 92% accuracy. The host genomic response to Influenza infection is robust and may provide the means for detection before typical clinical symptoms are apparent.
dc.language eng
dc.relation.ispartof PLoS One
dc.relation.isversionof 10.1371/journal.pone.0052198
dc.subject Female
dc.subject Host-Pathogen Interactions
dc.subject Humans
dc.subject Influenza A Virus, H1N1 Subtype
dc.subject Influenza A Virus, H3N2 Subtype
dc.subject Influenza, Human
dc.subject Male
dc.subject Middle Aged
dc.subject Oligonucleotide Array Sequence Analysis
dc.subject Reverse Transcriptase Polymerase Chain Reaction
dc.subject Species Specificity
dc.subject Time Factors
dc.subject Transcriptome
dc.subject Young Adult
dc.title A host transcriptional signature for presymptomatic detection of infection in humans exposed to influenza H1N1 or H3N2.
dc.type Journal article
pubs.author-url http://www.ncbi.nlm.nih.gov/pubmed/23326326
pubs.begin-page e52198
pubs.issue 1
pubs.organisational-group Basic Science Departments
pubs.organisational-group Biomedical Engineering
pubs.organisational-group Biostatistics & Bioinformatics
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Duke
pubs.organisational-group Duke Cancer Institute
pubs.organisational-group Electrical and Computer Engineering
pubs.organisational-group Global Health Institute
pubs.organisational-group Institutes and Centers
pubs.organisational-group Institutes and Provost's Academic Units
pubs.organisational-group Medicine
pubs.organisational-group Medicine, Cardiology
pubs.organisational-group Medicine, Infectious Diseases
pubs.organisational-group Molecular Genetics and Microbiology
pubs.organisational-group Pathology
pubs.organisational-group Pratt School of Engineering
pubs.organisational-group School of Medicine
pubs.organisational-group School of Nursing
pubs.organisational-group School of Nursing - Secondary Group
pubs.organisational-group Social Science Research Institute
pubs.organisational-group University Institutes and Centers
pubs.publication-status Published
pubs.volume 8
dc.identifier.eissn 1932-6203


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