A host transcriptional signature for presymptomatic detection of infection in humans exposed to influenza H1N1 or H3N2.
A host transcriptional signature for presymptomatic detection of infection in humans exposed to influenza H1N1 or H3N2.
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DOI：
10.1371/journal.pone.0052198
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Ginsburg GS
中科院分区：
文献类型：
--
作者：
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 3rd;Ramsburg E;Glickman S;Lucas JE;Carin L;Ginsburg GS
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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通讯作者：
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通讯作者：
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通讯作者：
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