title: A host transcriptional signature for presymptomatic detection of infection in humans exposed to influenza H1N1 or H3N2.
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.
authors: Institute for Genome Sciences and Policy, Duke University Medical Center, Durham, North Carolina, USA. chris.woods@duke.edu
authors: Christopher W
authors: CW
authors: Woods
authors: Micah T
authors: MT
authors: McClain
authors: Minhua
authors: M
authors: Chen
authors: Aimee K
authors: AK
authors: Zaas
authors: Bradly P
authors: BP
authors: Nicholson
authors: Jay
authors: J
authors: Varkey
authors: Timothy
authors: T
authors: Veldman
authors: Stephen F
authors: SF
authors: Kingsmore
authors: Yongsheng
authors: Y
authors: Huang
authors: Robert
authors: R
authors: Lambkin-Williams
authors: Anthony G
authors: AG
authors: Gilbert
authors: Alfred O
authors: AO
authors: Hero
authors: Elizabeth
authors: E
authors: Ramsburg
authors: Seth
authors: S
authors: Glickman
authors: Joseph E
authors: JE
authors: Lucas
authors: Lawrence
authors: L
authors: Carin
authors: Geoffrey S
authors: GS
authors: Ginsburg
mesh_terms: D005260:Female; D054884:Host-Pathogen Interactions; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000502:physiology*; D053122:Influenza A Virus, H3N2 Subtype / Q000502:physiology*; D007251:Influenza, Human / Q000175:diagnosis / Q000235:genetics* / Q000821:virology*; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013045:Species Specificity; D013997:Time Factors; D059467:Transcriptome; D055815:Young Adult