A crowdsourced analysis to identify ab initio molecular signatures predictive of susceptibility to viral infection
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Oct 24, 2018
- Source ID
- 10.1038/s41467-018-06735-8
Entities
People
- Aarthi Talla
- Alicia Amadoz
- Alok Sharma
- Ana Stanescu
- Benno Schwikowski
- Bertrand Miannay
- Cankut Cubuk
- Carito Guziolowski
- Chengzhe Tian
- Chi Pak
- Christofer Flinta
- Christopher Chiu
- Christopher W Woods
- Deepak Singla
- Di He
- Domenico Borzacchielo
- Ehsan Saghapour
- Emna Ben Abdallah
- Ephraim L Tsalik
- Erika Bongen
- Farnoosh Abbas Aghababazadeh
- Feng Yang
- Francisco Chinesta
- Gaurav Pandey
- Geoffrey S Ginsburg
- Harsh Saini
- Hiroki Sato
- Iryna Nikolayeva
- Ivan Stojković
- Jiadong Ji
- Jiayi Hou
- Joaquin Dopazo
- Jose Carbonell-caballero
- Joshua Burkhart
- Ka Yee Yeung
- Katsumi Inoue
- Kevin Bleakley
- Kumardeep Chaudhary
- Lara M. Mangravite
- Laura L. Elo
- Lei Xie
- Lewis E. Tomalin
- Li Qian
- Maria K Jaakkola
- Maria Suprun
- Marta R. Hidalgo
- Mehmet Eren Ahsen
- Mehrad Mahmoudian
- Micah T McClain
- Michał Łopuszyński
- Miron Bartosz Kursa
- Misbah Razzaq
- Mohammed Mahbubur Rahman
- Morgan Magnin
- Motoki Shiga
- Olivier Roux
- Pengcheng Lu
- Philipp Bucher
- Prasad Chodavarapu
- Reem Almugbel
- Ricardo Henao
- Riku Klén
- Ritesh Kumar
- Robert Vogel
- Ronesh Sharma
- Ryan D Chow
- S. Kumar
- Samad Jahandideh
- Sandeep Kumar Dhanda
- Shamim Sarhadi
- Sherry Bhalla
- Slim Fourati
- Solveig K Sieberts
- The Respiratory Viral Dream Challenge Consortium
- Thomas Cokelaer
- Thomas Faux
- Thomas Yu
- Tomi Suomi
- Tony Ribeiro
- Torbjörn Nordling
- Weiguang Mao
- Xiao Liang
- Yu Xiang
- Zafer Aydın
- Zoran Obradović
Organizations
- National Institutes of Health