Metabolic profiles of HbSC and HbSS RBCs. (A) Principal component analysis of metabolomics profiles performed on RBCs from HbAA (n = 10; mixed sex), HbSC (n = 12; mixed sex), and HbSS mice (n = 6; mixed sex). (B) Shared and differentially enriched metabolites in RBCs of HbSC and HbSS mice compared to those in HbAA mice (|fold change| ≥ 1.2; P ≤ .05, by unpaired t test). (C) Heat map showing the top 50 differentially enriched metabolites in RBCs from HbAA (n = 10), HbSC (n = 12), and HbSS mice (n = 6). (D) Heat map showing the top 25 differentially enriched metabolites shared between HbSC and HbSS RBCs compared to HbAA RBCs (|fold change| ≥ 1.2; P ≤ .05, by unpaired t-test). (E) Top metabolite sets associated with shared metabolites in HbSC and HbSS RBCs. The top enriched metabolites sets were identified by metabolite set enrichment analysis using MetaboAnalyst v.5.0. (F) Heat map showing the top 25 differentially enriched metabolites in HbSC RBCs relative to HbSS RBCs compared to HbAA RBCs (|fold change| ≥ 1.2; P ≤ .05, by unpaired t-test). (G) Top metabolite sets associated with HbSC-enriched metabolites.