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

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.