Balancing precision versus cohort transcriptomic analysis of acute and recovery phase of viral bronchiolitis

Author:

Gupta Ruchir12,Leimanis Mara L.13,Adams Marie4,Bachmann André S.1,Uhl Katie L.12,Bupp Caleb P.5,Hartog Nicholas L.6,Kort Eric J.17,Olivero Rosemary18,Comstock Sarah S.9,Sanfilippo Dominic J.13,Lunt Sophia Y.1011ORCID,Prokop Jeremy W.12ORCID,Rajasekaran Surender1312

Affiliation:

1. Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, Grand Rapids, Michigan

2. Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan

3. Pediatric Intensive Care Unit, Helen DeVos Children’s Hospital, Grand Rapids, Michigan

4. Genomics Core Facility, Van Andel Institute, Grand Rapids, Michigan

5. Spectrum Health Medical Genetics, Grand Rapids, Michigan

6. Allergy & Immunology, Spectrum Health, Grand Rapids, Michigan

7. DeVos Cardiovascular Research Program, Spectrum Health and Van Andel Institute, Grand Rapids, Michigan

8. Infectious Disease, Helen DeVos Children’s Hospital, Grand Rapids, Michigan

9. Department of Food Science and Human Nutrition, Michigan State University, East Lansing, Michigan

10. Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan

11. Chemical Engineering and Materials Science, Michigan State University, East Lansing, Michigan

12. Office of Research, Spectrum Health, Grand Rapids, Michigan

Abstract

Viral infections affecting the lower respiratory tract place enormous burdens on hospitals. As neither vaccines nor antiviral agents exist for many viruses, understanding risk factors and outcomes in each patient using minimally invasive analysis, such as blood, can lead to improved health care delivery. A cohort of PAXgene RNA sequencing of infants admitted with moderate or severe acute bronchiolitis and respiratory syncytial virus were compared with case-control statistical analysis and cohort-based outlier mapping for precision transcriptomics. Patients with severe bronchiolitis had signatures connected to the immune system, interferon signaling, and cytokine signaling, with marked sex differences in XIST, RPS4Y1, KDM5D, and LINC00278 for severity. Several patients had unique secondary infections, cytokine activation, immune responses, biological pathways, and immune cell activation, highlighting the need for defining patient-level transcriptomic signatures. Balancing relative contributions of cohort-based biomarker discoveries with patient’s biological responses is needed to understand the totality of mechanisms of adverse outcomes in viral bronchiolitis.

Funder

Helen Devos childrens Hospital Foundation

HHS | NIH | National Institute of Environmental Health Sciences

Michigan State University

Publisher

American Physiological Society

Subject

Cell Biology,Physiology (medical),Pulmonary and Respiratory Medicine,Physiology

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