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JUMPn: A Streamlined Application for Protein Co-Expression Clustering and Network Analysis in Proteomics
Published on: October 19, 2021
Network Analysis Reveals Protein Modules Associated with Childhood Respiratory Diseases
Nicole Prince1,2, Sofina Begum1,2, Kevin M Mendez1,2,3
1Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Insights
Infant immune protein profiles at age 1 predict childhood respiratory diseases like asthma and infections by age 6. These early immune markers are linked to environmental exposures and metabolic changes, offering new ways to identify at-risk children.
Area of Science:
- Immunology
- Pediatric Respiratory Medicine
- Systems Biology
Background:
- The first year of life is critical for immune system development, influencing long-term respiratory health.
- Early life immune trajectories impact the risk of asthma, recurrent infections, and eczema.
- The biological mechanisms linking early immunity to later respiratory disease are not well understood.
Purpose of the Study:
- To investigate the association between immune-related protein profiles in infants and the subsequent development of childhood respiratory diseases.
- To identify early immune biomarkers that predict respiratory disease incidence up to age 6.
- To explore genomic, environmental, and metabolomic factors associated with these early immune profiles.
Main Methods:
- Weighted gene correlation network analysis (WGCNA) was used to identify modules of correlated immune proteins in plasma from 294 children at age 1.
- Regression analyses assessed the relationship between protein modules and respiratory disease incidence (asthma, recurrent wheeze, infections, eczema) by age 6.
- Genomic, environmental, and metabolomic data were analyzed to characterize associated factors.
Main Results:
- Four protein modules at age 1 were significantly associated with childhood asthma, recurrent wheeze, respiratory infections, or eczema by age 6.
- Three modules showed associations with environmental exposures and disrupted metabolomic pathways.
- No significant genome-wide single nucleotide polymorphisms (SNPs) were identified as risk factors for the protein modules.
Conclusions:
- Early life (age 1 year) immune protein profiles can predict the development of respiratory diseases up to age 6.
- These predictive profiles are linked to metabolic pathway alterations, particularly in amino acid and energy metabolism.
- Immune protein profiling in infancy may offer novel strategies for identifying children at risk for respiratory conditions.
Background:
The first year of life is a period of rapid immune development that can impact health trajectories and the risk of developing respiratory-related diseases, such as asthma, recurrent infections, and eczema. However, the biology underlying subsequent disease development remains unknown.
Methods:
Using weighted gene correlation network analysis (WGCNA), we derived modules of highly correlated immune-related proteins in plasma samples from children at age 1 year (N=294) from the Vitamin D Antenatal Asthma Reduction Trial (VDAART). We applied regression analyses to assess relationships between protein modules and development of childhood respiratory diseases up to age 6 years. We then characterized genomic, environmental, and metabolomic factors associated with modules.
Results:
WGCNA identified four protein modules at age 1 year associated with incidence of childhood asthma and/or recurrent wheeze (Padj range: 0.02-0.03), respiratory infections (Padj range: 6.3×10-9-2.9×10-6), and eczema (Padj=0.01) by age 6 years; three modules were associated with at least one environmental exposure (Padj range: 2.8×10-10-0.03) and disrupted metabolomic pathway(s) (Padj range: 2.8×10-6-0.04). No genome-wide SNPs were identified as significant genetic risk factors for any protein module. Relationships between protein modules with clinical, environmental, and 'omic factors were temporally sensitive and could not be recapitulated in protein profiles at age 6 years.
Conclusion:
These findings suggested protein profiles as early as age 1 year predicted development of respiratory-related diseases through age 6 and were associated with changes in pathways related to amino acid and energy metabolism. These may inform new strategies to identify vulnerable individuals based on immune protein profiling.
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