Network analysis reveals protein modules associated with childhood respiratory diseases
Author Identifier
Kevin M. Mendez: https://orcid.org/0000-0002-8832-2607
Document Type
Journal Article
Publication Title
Journal of Allergy and Clinical Immunology
PubMed ID
40057284
Publisher
Elsevier
School
Centre for Integrative Metabolomics and Computational Biology / School of Science
Publication Unique Identifier
10.1016/j.jaci.2025.02.030
Funders
National Institutes of Health (R01HL123915, R01HL141826, K01HL146980, K01HL175261, T32HL007427, U19AI168643)
Abstract
Background: The first year of life represents a dynamic immune development period that impacts the risk of developing respiratory-related diseases, including asthma, recurrent infections, and eczema. However, the role of immune-mediating proteins in childhood respiratory diseases is not well characterized in early life. Objective: The objective of this study was to investigate relationships between protein profiles at age 1 year and respiratory-related diseases by age 6 years, including asthma, recurrent wheeze, respiratory infections, and eczema. Methods: We applied weighted gene correlation network analysis to derive modules of highly correlated proteins during early life immune development using plasma samples collected from children at age 1 year (n = 294) in the Vitamin D Antenatal Asthma Reduction Trial. Using regression analysis, we evaluated relationships between protein modules at age 1 and respiratory-related diseases by age 6. We integrated protein modules with additional omics and social, demographic, and environmental data for further characterization. Results: Our analysis identified 4 protein modules at age 1 year associated with incidence of childhood asthma and/or recurrent wheeze (adjusted Ps = .02 to .03), respiratory infections (adjusted Ps = 6.3 × 10−9 to 2.9 × 10−6), and eczema (adjusted P = .01) by age 6 years; associations between modules and clinical outcomes were temporally sensitive and were not recapitulated using protein profiles at age 6 years. Age 1 modules were associated with environmental factors (adjusted Ps = 2.8 × 10−10 to .03) and alterations in metabolomic pathways (adjusted Ps = 2.8 × 10−6 to .04). No genome-wide single nucleotide polymorphisms were identified for any protein module. Conclusion: These findings suggested that protein profiles at age 1 year predicted development of respiratory-related diseases by age 6. Applying network approaches to study protein profiles may represent a new strategy to identify children susceptible to respiratory-related diseases in the first year of life.
DOI
10.1016/j.jaci.2025.02.030
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Comments
Prince, N., Begum, S., Mendez, K. M., Ramirez, L. G., Chen, Y., Chen, Q., ... & Lasky-Su, J. A. (2025). Network analysis reveals protein modules associated with childhood respiratory diseases. Journal of Allergy and Clinical Immunology. Advance online publication. https://doi.org/10.1016/j.jaci.2025.02.030