A crowdsourced analysis to identify ab initio molecular signatures predictive of susceptibility to viral infection

Slim Fourati, Aarthi Talla, Mehrad Mahmoudian, Joshua G. Burkhart, Riku Klén, Ricardo Henao, Zafer Aydın, Ka Yee Yeung, Mehmet Eren Ahsen, Reem Almugbel, Samad Jahandideh, Xiao Liang, Torbjörn E. M. Nordling, Motoki Shiga, Ana Stanescu, Robert Vogel, The Respiratory Viral DREAM Challenge Consortium, Gaurav Pandey, Christopher Chiu, Micah T. McClain, Chris W. Woods, Geoffrey S. Ginsburg, Laura L. Elo, Ephraim L. Tsalik, Lara M. Mangravite, and Solveig K. Sieberts

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May 07, 2018
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Received: 30th April 18

Respiratory viruses are highly infectious; however, the variation of individuals' physiologic responses to viral exposure is poorly understood. Most studies examining molecular predictors of response focus on late stage predictors, typically near the time of peak symptoms. To determine whether pre- or early post-exposure factors could predict response, we conducted a community-based analysis to identify predictors of resilience or susceptibility to several respiratory viruses (H1N1, H3N2, Rhinovirus, and RSV) using peripheral blood gene expression profiles collected from healthy subjects prior to viral exposure, as well as up to 24 hours following exposure. This analysis revealed that it is possible to construct models predictive of symptoms using profiles even prior to viral exposure. Analysis of predictive gene features revealed little overlap among models; however, in aggregate, these genes were enriched for common pathways. Heme Metabolism, the most significantly enriched pathway, was associated with higher risk of developing symptoms following viral exposure.

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This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.

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Nature Communications

Nature Research, Springer Nature

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