A systems genomics approach uncovers molecular associates of RSV severity

Authors

Matthew N. McCall, Department of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester New York, United States of America.
Chin-Yi Chu, Division of Neonatology and Pediatric Molecular and Personalized Medicine Program, University of Rochester Medical Center, Rochester New York, United States of America.
Lu Wang, Department of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester New York, United States of America.
Lauren Benoodt, Department of Biochemistry and Biophysics, University of Rochester Medical Center, Rochester New York, United States of America.
Juilee Thakar, Department of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester New York, United States of America.
Anthony Corbett, Department of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester New York, United States of America.
Jeanne Holden-Wiltse, Department of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester New York, United States of America.
Christopher Slaunwhite, Division of Neonatology and Pediatric Molecular and Personalized Medicine Program, University of Rochester Medical Center, Rochester New York, United States of America.
Alex Grier, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester New York, United States of America.
Steven R. Gill, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester New York, United States of America.
Ann R. Falsey, Rochester Regional HealthFollow
David J. Topham, Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester New York, United States of America.
Mary T. Caserta, Department of Pediatrics, University of Rochester Medical Center, Rochester New York, United States of America.
Edward E. Walsh, Rochester Regional HealthFollow
Xing Qiu, Department of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester New York, United States of America.
Thomas J. Mariani, Division of Neonatology and Pediatric Molecular and Personalized Medicine Program, University of Rochester Medical Center, Rochester New York, United States of America.

Department

Infectious Diseases

Document Type

Article

Publication Title

PLoS Computational Biology

Abstract

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.

First Page

e1009617

DOI

10.1371/journal.pcbi.1009617

Volume

17

Issue

12

Publication Date

12-28-2021

PubMed ID

34962914

Recommended Citation

McCall, M. N., Chu, C., Wang, L., Benoodt, L., Thakar, J., Corbett, A., Holden-Wiltse, J., Slaunwhite, C., Grier, A., Gill, S. R., Falsey, A. R., Topham, D. J., Caserta, M. T., Walsh, E. E., Qiu, X., & Mariani, T. J. (2021). A systems genomics approach uncovers molecular associates of RSV severity. PLoS Computational Biology, 17 (12), e1009617. https://doi.org/10.1371/journal.pcbi.1009617