Woods, Christopher WMcClain, Micah TChen, MinhuaZaas, Aimee KNicholson, Bradly PVarkey, JayVeldman, TimothyKingsmore, Stephen FKingsmore, Stephen FHuang, YongshengLambkin-Williams, RobertGilbert, Anthony GHero, Alfred ORamsburg, ElizabethGlickman, SethLucas, Joseph ECarin, LawrenceGinsburg, Geoffrey STse, Herman2014-07-222013https://hdl.handle.net/10161/8944There 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.FemaleHost-Pathogen InteractionsHumansInfluenza A Virus, H1N1 SubtypeInfluenza A Virus, H3N2 SubtypeInfluenza, HumanMaleMiddle AgedOligonucleotide Array Sequence AnalysisReverse Transcriptase Polymerase Chain ReactionSpecies SpecificityTime FactorsTranscriptomeYoung AdultJournal article1932-6203