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

TitleA crowdsourced analysis to identify ab initio molecular signatures predictive of susceptibility to viral infection.
Publication TypeJournal Article
Year of Publication2018
AuthorsFourati, S, Talla, A, Mahmoudian, M, Burkhart, JG, Klén, R, Henao, R, Yu, T, Aydın, Z, Yeung, KYee, Ahsen, MEren, Almugbel, R, Jahandideh, S, Liang, X, Nordling, TEM, Shiga, M, Stanescu, A, Vogel, R, Pandey, G, Chiu, C, McClain, MT, Woods, CW, Ginsburg, GS, Elo, LL, Tsalik, EL, Mangravite, LM, Sieberts, SK
Corporate AuthorsRespiratory Viral DREAM Challenge Consortium
JournalNat Commun
Volume9
Issue1
Pagination4418
Date Published2018 Oct 24
ISSN2041-1723
Abstract

The response to respiratory viruses varies substantially between individuals, and there are currently no known molecular predictors from the early stages of infection. Here we conduct a community-based analysis to determine whether pre- or early post-exposure molecular factors could predict physiologic responses to viral exposure. Using peripheral blood gene expression profiles collected from healthy subjects prior to exposure to one of four respiratory viruses (H1N1, H3N2, Rhinovirus, and RSV), as well as up to 24 h following exposure, we find that it is possible to construct models predictive of symptomatic response using profiles even prior to viral exposure. Analysis of predictive gene features reveal little overlap among models; however, in aggregate, these genes are enriched for common pathways. Heme metabolism, the most significantly enriched pathway, is associated with a higher risk of developing symptoms following viral exposure. This study demonstrates that pre-exposure molecular predictors can be identified and improves our understanding of the mechanisms of response to respiratory viruses.

DOI10.1038/s41467-018-06735-8
Alternate JournalNat Commun
PubMed ID30356117
PubMed Central IDPMC6200745
Grant ListW911NF-15-1-0107 / / DOD | Defense Advanced Research Projects Agency (DARPA) /
W911NF-15-1-0107 / / DOD | Defense Advanced Research Projects Agency (DARPA) /
W911NF-15-1-0107 / / DOD | Defense Advanced Research Projects Agency (DARPA) /
W911NF-15-1-0107 / / DOD | Defense Advanced Research Projects Agency (DARPA) /
U54 HL127624 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) /
R01GM114434 / / U.S. Department of Health & Human Services | National Institutes of Health (NIH) /