An Integrative Transcriptomic and Metabolomic Study of Lung Function in Children With Asthma

Abstract

The results of this hypothesis-generating study suggest a mechanistic basis for multiple asthma genes, including ORMDL3, and a role for lipid metabolism. They demonstrate that integrating multiple omic technologies may provide a more informative picture of asthmatic lung function biology than single omic analyses.

Precision Medicine in Childhood Asthma: Omic Studies of Treatment Response

“…Remarkably, in recent years, the number of pharmacogenomic, epigenomic, and metabolomic studies that included ethnically diverse minority populations such as African Americans and Hispanic/Latinos have increased compared to the past [25][26][27]38,63,82,83]. However, studies in populations of Asian ancestry remain still scarce [51].…”

“…While single omics have contributed to revealing some insights on the basis of treatment response, in many cases, they focus on single-marker approaches, limiting its predictive power and clinic transferability. As an example of success, system biology has been applied to transcriptomics [52] and metabolomics [63] data to identify multiple co-expressed markers and the underlying biologic pathways they are involved in. Further validation should also be sought by ex-vivo studies and directed to the development of panels of biomarkers with clinical applicability.…”

“…Further validation should also be sought by ex-vivo studies and directed to the development of panels of biomarkers with clinical applicability. Moreover, many studies have investigated whole tissues with a heterogeneous composition of multiple cell types [38,39,49,51,63], but more initiatives to refine specific cell-type patterns in disease-relevant tissues are required. Besides, while replication attempts are a common practice among pharmacogenomic studies, this strategy should expand to other omics, especially when sample sizes are limited.…”

“…Moreover, Kelly et al also conducted a multiomic study of lung function in Hispanic/Latino children with asthma (n = 325) [63]. In an integrative approach to identify modules of coregulated gene transcripts and metabolites, a total of 25,060 transcripts and 8185 metabolites from whole blood were clustered using WGCNA.…”

Plasma 25-Hydroxyvitamin D Concentrations are Associated with Polyunsaturated Fatty Acid Metabolites in Young Children: Results from the Vitamin D Antenatal Asthma Reduction Trial

“…Our replication analysis included children in CAMP with both serum 25(OH)D [52] and metabolomics data at baseline (n = 542) or end of the trial (n = 561), respectively. Metabolomic profiling in serum samples was conducted at The Broad Institute [53,54] (details in Supplementary File 1). Equivalent models to the primary analyses in VDAART were employed for 501 named metabolites, with two adjustments: (1) we removed asthma status from the models since all children in CAMP were asthmatics, and (2) we adjusted for age at sampling since CAMP was not a birth cohort.…”