Metabolomics analyses of T21 vs D21 RBCs. (A) UHPLC-MS metabolomic analyses were performed on RBCs from male or female disomic and trisomic volunteers. (B) Metabolite levels were correlated to each other and to age to identify variations (Δ|r| > 30%) in metabolite levels secondary to metabolic rewiring in DS, sex, or aging. The rationale behind this analysis is that, even though correlation does not necessarily imply causation, metabolites in the same pathway will show significant correlations to each other owing to biochemical constraints governing the kinetics of the rate-limiting enzymes from that pathway, a concept we previously referred to as the metabolic linkage.24 Phenotypic alterations that disrupted this fine tuning of the kinetics of specific metabolic pathways would be highlighted by a differential analysis of correlation of metabolites across conditions (ie, in this case D21 and T21). (C) Shown from left to right is an overview of correlations across metabolites in D21 and T21 subjects (blue to red = −1 < r < +1) as well as a highlight of correlations varying >30% between these 2 conditions (highlighted in green).
