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

Publication ,  Journal Article
Woods, CW; McClain, MT; Chen, M; Zaas, AK; Nicholson, BP; Varkey, J; Veldman, T; Kingsmore, SF; Huang, Y; Lambkin-Williams, R; Gilbert, AG ...
Published in: PLoS One
2013

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.

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Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2013

Volume

8

Issue

1

Start / End Page

e52198

Location

United States

Related Subject Headings

  • Young Adult
  • Transcriptome
  • Time Factors
  • Species Specificity
  • Reverse Transcriptase Polymerase Chain Reaction
  • Oligonucleotide Array Sequence Analysis
  • Middle Aged
  • Male
  • Influenza, Human
  • Influenza A Virus, H3N2 Subtype
 

Citation

APA
Chicago
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MLA
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Woods, C. W., McClain, M. T., Chen, M., Zaas, A. K., Nicholson, B. P., Varkey, J., … Ginsburg, G. S. (2013). A host transcriptional signature for presymptomatic detection of infection in humans exposed to influenza H1N1 or H3N2. PLoS One, 8(1), e52198. https://doi.org/10.1371/journal.pone.0052198
Woods, Christopher W., Micah T. McClain, Minhua Chen, Aimee K. Zaas, Bradly P. Nicholson, Jay Varkey, Timothy Veldman, et al. “A host transcriptional signature for presymptomatic detection of infection in humans exposed to influenza H1N1 or H3N2.PLoS One 8, no. 1 (2013): e52198. https://doi.org/10.1371/journal.pone.0052198.
Woods CW, McClain MT, Chen M, Zaas AK, Nicholson BP, Varkey J, et al. A host transcriptional signature for presymptomatic detection of infection in humans exposed to influenza H1N1 or H3N2. PLoS One. 2013;8(1):e52198.
Woods, Christopher W., et al. “A host transcriptional signature for presymptomatic detection of infection in humans exposed to influenza H1N1 or H3N2.PLoS One, vol. 8, no. 1, 2013, p. e52198. Pubmed, doi:10.1371/journal.pone.0052198.
Woods CW, McClain MT, Chen M, Zaas AK, Nicholson BP, Varkey J, Veldman T, Kingsmore SF, Huang Y, Lambkin-Williams R, Gilbert AG, Hero AO, Ramsburg E, Glickman S, Lucas JE, Carin L, Ginsburg GS. A host transcriptional signature for presymptomatic detection of infection in humans exposed to influenza H1N1 or H3N2. PLoS One. 2013;8(1):e52198.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2013

Volume

8

Issue

1

Start / End Page

e52198

Location

United States

Related Subject Headings

  • Young Adult
  • Transcriptome
  • Time Factors
  • Species Specificity
  • Reverse Transcriptase Polymerase Chain Reaction
  • Oligonucleotide Array Sequence Analysis
  • Middle Aged
  • Male
  • Influenza, Human
  • Influenza A Virus, H3N2 Subtype