TY - JOUR T1 - A Host Transcriptional Signature for Presymptomatic Detection of Infection in Humans Exposed to Influenza H1N1 or H3N2 A1 - Woods, Christopher W. A1 - McClain, Micah T. A1 - Chen, Minhua A1 - Zaas, Aimee K. A1 - Nicholson, Bradly P. A1 - Varkey, Jay A1 - Veldman, Timothy A1 - Kingsmore, Stephen F. A1 - Huang, Yongsheng A1 - Lambkin-Williams, Robert A1 - Gilbert, Anthony G. A1 - Hero, Alfred O., III A1 - Ramsburg, Elizabeth A1 - Glickman, Seth A1 - Lucas, Joseph E. A1 - Carin, Lawrence A1 - Ginsburg, Geoffrey S. Y1 - 2013/01/09 N2 - 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. JF - PLOS ONE JA - PLOS ONE VL - 8 IS - 1 UR - https://doi.org/10.1371/journal.pone.0052198 SP - e52198 EP - PB - Public Library of Science M3 - doi:10.1371/journal.pone.0052198 ER -