Multi-omics integration reveals BPGM downregulation and potential plasma metabolite biomarkers for childhood asthma

<h4>Objective</h4>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.<h4>Methods</h4>In this exploratory multi-omics study, we integrated public transcriptomic data (GSE35571, <i>n</i> = 124 samples: 60 asthma, 64 controls) with in-house untargeted metabolomics (<i>n</i> = 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.<h4>Results</h4>Transcriptomics identified 15 differentially expressed genes (<i>p</i> < 0.05, |log₂FC| > 0.25), including significant BPGM downregulation (log₂FC = -0.2731, <i>p</i> = 0.0422). Metabolomics revealed 516 differential metabolites [<i>p</i> < 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 (<i>r</i> = 0.469, <i>p</i> = 0.009) and eosinophil counts (<i>r</i> = 0.506, <i>p</i> = 0.004), while no significant correlations were observed with pulmonary function parameters.<h4>Conclusions</h4>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.