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

Am J Physiol Lung Cell Mol Physiol. 2021 Jun 1;320(6):L1147-L1157. doi: 10.1152/ajplung.00440.2020. Epub 2021 Apr 14.

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.

Keywords: immune system; precision medicine; respiratory syncytial virus; transcriptomics; viral bronchiolitis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bronchiolitis, Viral / blood
  • Bronchiolitis, Viral / virology*
  • Humans
  • Minor Histocompatibility Antigens / pharmacology*
  • Respiratory Syncytial Virus Infections / drug therapy*
  • Respiratory Syncytial Virus Infections / immunology
  • Respiratory Syncytial Virus, Human / drug effects
  • Respiratory Syncytial Virus, Human / pathogenicity
  • Severity of Illness Index
  • Transcriptome / drug effects*
  • Transcriptome / immunology
  • Virus Diseases / drug therapy
  • Virus Diseases / virology

Substances

  • Minor Histocompatibility Antigens