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Publication
Journal of Allergy & Clinical Immunology

Network Analysis Reveals Protein Modules Associated with Childhood Respiratory Diseases

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  • March 6, 2025
  • Jessica Lasky-Su, PhD, Brigham and Women's Hospital
Topic/Product:
Inflammation, Inflammation Panel 250
Disease Area:
Childhood Respiratory Diseases
Sample Type:
Plasma

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.
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Authors & Affiliations

Nicole Prince, Sofina Begum, Kevin M Mendez, Lourdes G Ramirez, Yulu Chen, Qingwen Chen, Su H Chu, Priyadarshini Kachroo, Ofer Levy, Joann Diray-Arce, Paolo Palma, Augusto A Litonjua, Scott T Weiss, Rachel S Kelly, Jessica A Lasky-Su

Channing Division of Network Medicine, Brigham and Women’s Hospital

Harvard Medical School

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Steve Williams, MD, PhD

CSO

Dr. Willams serves as the company’s Chief Scientific Officer. He was previously Chief Medical Officer at Standard Biotools and at SomaLogic where he pioneered the discipline for discovery and validation of predictive, diagnostic and prognostic models using machine-learning applied to large-plex proteomics. 20 such tests were used for drug characterization, safety and efficacy when incorporated in clinical drug trials at Pharma/Biotech and 17 different multivariate tests were validated and translated into regulated healthcare uses. Prior to SomaLogic, Dr. Williams was at Pfizer in the UK and the USA as a clinical triallist in Translational Medicine, and subsequently as VP, Global Clinical Technology. He sat on the National Advisory Council for the National Institute of Biomedical Imaging and Bioengineering, the Executive Committee for the FNIH Biomarkers Consortium, and worked with FDA and PhRMA on developing evidentiary standards for biomarker qualification. Dr. William’s medical training was in London, at Charing Cross and Westminster Medical School, followed by a PhD in medicine/physiology at the same institution and training in Radiology at the University of Newcastle Upon Tyne. Steve is co-inventor on 26 proteomics patents and author/coauthor on multiple foundational proteomics manuscripts.

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Justin McAnear

CFO

Mr. McAnear serves as the company’s Chief Financial Officer. He brings over 25 years of operational and financial leadership experience across various sectors and was instrumental in taking 10x Genomics public in 2019, serving as its CFO for over five years. Mr. McAnear served for over 3 years as Tesla’s VP of Worldwide Finance and Operations, supporting landmark initiatives such as the Model X and Model 3 launches and Solar City acquisition.  He also held various roles at Apple and J&J earlier in his career and served as a naval officer and aviator for over 9 years.