Open AccessA systems genomics approach uncovers molecular associates of RSV severity
Author(s) -
Matthew N. McCall,
Chin-Yi Chu,
Lu Wang,
Lauren Benoodt,
Juilee Thakar,
Anthony Corbett,
Jeanne HoldenWiltse,
Christopher Slaunwhite,
Alex Grier,
Steven R. Gill,
Ann R. Falsey,
David J. Topham,
Mary T. Caserta,
Edward E. Walsh,
Xing Qiu,
Thomas J. Mariani
Publication year - 2021
Publication title -
plos computational biology/plos computational biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.628
H-Index - 182
eISSN - 1553-7358
pISSN - 1553-734X
DOI - 10.1371/journal.pcbi.1009617
Subject(s) - immune system , innate immune system , immunology , biology , acquired immune system , virus , computational biology
Respiratory syncytial virus (RSV) infection results in millions of hospitalizations and thousands of deaths each year. Variations in the adaptive and innate immune response appear to be associated with RSV severity. To investigate the host response to RSV infection in infants, we performed a systems-level study of RSV pathophysiology, incorporating high-throughput measurements of the peripheral innate and adaptive immune systems and the airway epithelium and microbiota. We implemented a novel multi-omic data integration method based on multilayered principal component analysis, penalized regression, and feature weight back-propagation, which enabled us to identify cellular pathways associated with RSV severity. In both airway and immune cells, we found an association between RSV severity and activation of pathways controlling Th17 and acute phase response signaling, as well as inhibition of B cell receptor signaling. Dysregulation of both the humoral and mucosal response to RSV may play a critical role in determining illness severity.