A systems genomics approach uncovers molecular associates of RSV severity

• Main Authors: Benoodt, L. (Author), Caserta, M.T (Author), Chu, C.-Y (Author), Corbett, A. (Author), Falsey, A.R (Author), Gill, S.R (Author), Grier, A. (Author), Holden-Wiltse, J. (Author), Mariani, T.J (Author), McCall, M.N (Author), Qiu, X. (Author), Slaunwhite, C. (Author), Thakar, J. (Author), Topham, D.J (Author), Walsh, E.E (Author), Wang, L. (Author)
• Format: Article
• Language: English
• Published: Public Library of Science 2021
• Subjects: adaptive immunity; Article; B lymphocyte receptor; cell activation; cohort analysis; controlled study; cytology; disease association; disease severity; gene expression regulation; genetics; genomics; Genomics; high throughput sequencing; human; Human respiratory syncytial virus; Humans; humoral immunity; Immunity, Innate; immunocompetent cell; immunology; infant; Infant; innate immunity; machine learning; Machine Learning; metabolism; Microbiota; microflora; molecular genetics; molecular pathology; Nasal Cavity; nonhuman; nose cavity; pathophysiology; procedures; respiratory epithelium; respiratory syncytial virus infection; Respiratory Syncytial Virus Infections; RNA-Seq; severity of illness index; Severity of Illness Index; signal transduction; Th17 cell
• Online Access: View Fulltext in Publisher
• ISBN: 1553734X (ISSN)
• DOI: 10.1371/journal.pcbi.1009617

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. © 2021 McCall et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.