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Absorption of Nasal and Bronchial Fluids: Precision Sampling of the Human Respiratory Mucosa and Laboratory Processing of Samples
Published on: January 21, 2018
Balancing precision versus cohort transcriptomic analysis of acute and recovery phase of viral bronchiolitis
Ruchir Gupta1,2, Mara L Leimanis1,3, Marie Adams4
1Department of Pediatrics and Human Development, College of Human Medicine, Michigan State University, Grand Rapids, Michigan.
Insights
This study reveals distinct immune system signatures in infants with severe acute bronchiolitis, identifying sex differences and unique patient responses. Understanding these viral infection patterns improves healthcare delivery.
Area of Science:
- Pediatric infectious diseases
- Molecular biology
- Genomics
Background:
- Lower respiratory tract viral infections pose significant healthcare burdens.
- Lack of vaccines and antivirals necessitates better risk factor and outcome analysis.
- Minimally invasive methods like blood analysis can improve patient care.
Purpose of the Study:
- To investigate transcriptomic signatures in infants with acute bronchiolitis.
- To identify molecular differences between moderate and severe cases.
- To explore sex-based variations in gene expression related to disease severity.
Main Methods:
- Utilized PAXgene RNA sequencing on infant cohorts with acute bronchiolitis.
- Employed case-control statistical analysis and cohort-based outlier mapping.
- Focused on precision transcriptomics for identifying molecular patterns.
Main Results:
- Severe bronchiolitis showed distinct immune, interferon, and cytokine signaling signatures.
- Significant sex differences were observed in specific gene expressions (XIST, RPS4Y1, KDM5D, LINC00278).
- Identified unique secondary infections, cytokine activation, and immune responses in individual patients.
Conclusions:
- Patient-level transcriptomic signatures are crucial for understanding adverse outcomes in viral bronchiolitis.
- Integrating cohort biomarkers with individual biological responses is essential.
- Precision medicine approaches can enhance healthcare for viral respiratory infections.
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.
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