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

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 in...

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Bibliographic Details
Published in:PloS one 2013-01, Vol.8 (1), p.e52198-e52198
Main Authors: Woods, Christopher W, McClain, Micah T, Chen, Minhua, Zaas, Aimee K, Nicholson, Bradly P, Varkey, Jay, Veldman, Timothy, Kingsmore, Stephen F, Huang, Yongsheng, Lambkin-Williams, Robert, Gilbert, Anthony G, Hero, 3rd, Alfred O, Ramsburg, Elizabeth, Glickman, Seth, Lucas, Joseph E, Carin, Lawrence, Ginsburg, Geoffrey S
Format: Article
Language:English
Subjects:
Analysis
Bacterial infections
Bioinformatics
Biology
Computer engineering
Development and progression
Emergency medical services
Epidemics
Female
Gene expression
Genes
Genetic aspects
Genetic research
Genomes
Genomics
Health aspects
Host-Pathogen Interactions
Humans
Impact analysis
Infections
Infectious diseases
Influenza
Influenza A
Influenza A Virus, H1N1 Subtype - physiology
Influenza A Virus, H3N2 Subtype - physiology
Influenza, Human - diagnosis
Influenza, Human - genetics
Influenza, Human - virology
Livestock
Male
Medicine
Middle Aged
Oligonucleotide Array Sequence Analysis
Pandemics
Peripheral blood
Regression analysis
Reverse Transcriptase Polymerase Chain Reaction
Species Specificity
Swine
Swine flu
Time Factors
Transcription
Transcription (Genetics)
Transcriptome
Viral infections
Virology
Young Adult
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Description
Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0052198