Research Article: Multi-omics integration reveals BPGM downregulation and potential plasma metabolite biomarkers for childhood asthma
Abstract:
This study aimed to identify potential diagnostic biomarkers and candidate therapeutic targets through multi-omics integration of peripheral blood transcriptomics and metabolomics in children with asthma. We specifically investigated the association between bisphosphoglycerate mutase (BPGM) downregulation and metabolic alterations in the glycine-serine-threonine pathway, seeking to explore potential mechanisms underlying asthma-related metabolic reprogramming.
In this exploratory multi-omics study, we integrated public transcriptomic data (GSE35571, n =?124 samples: 60 asthma, 64 controls) with in-house untargeted metabolomics ( n =?30 samples: 15 asthma, 15 controls) from treatment-naive, normal-weight children aged 6–14 years. The transcriptomic cohort was derived from a US population (Detroit, Michigan) while the metabolomic cohort was from Xinjiang, China. While this cross-population design precludes direct gene–metabolite correlation at the individual level, pathway-level convergence across ethnically and geographically distinct cohorts may suggest conserved disease-related biological processes, although the pathway intersection should be interpreted as indirect concordance supporting hypothesis generation rather than establishing mechanistic linkage.
Transcriptomics identified 15 differentially expressed genes ( p <?0.05, |log 2 FC|?>?0.25), including significant BPGM downregulation (log 2 FC?=??0.2731, p =?0.0422). Metabolomics revealed 516 differential metabolites [ p <?0.05, variable importance in projection (VIP)?>?1]. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway intersection identified glycine-serine-threonine metabolism (hsa00260) as the core shared pathway, enriched with BPGM and three upregulated metabolites: L-tryptophan, 5-aminolevulinic acid, and L-aspartate semialdehyde. These metabolites demonstrated good diagnostic performance with area under the curve (AUC) values of 0.818, 0.844, and 0.818, respectively. 5-Aminolevulinic acid showed optimal diagnostic accuracy with 80% sensitivity and 80% specificity. Spearman correlation analysis revealed that 5-aminolevulinic acid was significantly positively correlated with both serum IgE ( r =?0.469, p =?0.009) and eosinophil counts ( r =?0.506, p =?0.004), while no significant correlations were observed with pulmonary function parameters.
This preliminary multi-omics integration study identified concurrent BPGM downregulation and altered glycine-serine-threonine metabolism in childhood asthma. While these findings suggest a potential association between BPGM expression changes and metabolic alterations in this pathway, the proposed mechanistic link remains hypothetical and requires direct experimental validation.
Introduction:
Childhood asthma is the most common chronic respiratory disease in pediatric populations, with a global prevalence of approximately 10.2% ( 1 ). This disease exhibits remarkable heterogeneity due to complex interactions among genetic, immunological, environmental, and metabolic factors ( 2 ). Although inhaled corticosteroid-based therapies have been widely adopted, some patients experience inadequate symptom control and progress to severe or refractory asthma ( 3 ). Therefore, there is an urgent need to elucidate…
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