Untargeted Metabolomics Identifies Potential Hypertrophic Cardiomyopathy Biomarkers in Carriers of MYBPC3 Founder Variants

Figures

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  Figure 1. Relative variable importance. Top 25 metabolites in each model ordered by their mean relative importance across the models, showing their relative importance scaled to the most important metabolite in each model. The sPLS-DA and XGBoost models show 26 and 30 metabolites, respectively, as these metabolites were included in the top 25 of other models. Two metabolites selected by the Lasso logistic regression, Ceramide (t18:0/16:0) and 4-Trimethylammoniobutanal, are not visible owing to their very small coefficients (−8.67 × 10−7 and 1.82 × 10−6, respectively). Metabolites annotated to the same mass spectrometry peak are denoted in square brackets. sPLS-DA, sparse partial least squares discriminant analysis. * includes 2-methoxy-estradiol-17b 3-glucuronide and 4-hydroxyandrostenedione glucuronide. † includes aspartyl-(iso)leucine, L-beta-aspartyl-L-leucine, (gamma-)glutamylvaline, and (iso)leucyl-aspartate. ‡ includes 1,3-dimethyluracil, imidazolepropionic acid, and (Pi-)methylimidazoleacetic acid. § includes (S)-3,4-/2,4-dihydroxybutyric acid, 4-deoxythreonic/-erythronic acid, erythrose, and L-erythrulose. ‖ includes dextrin, D-Gal alpha 1- > 6D-Gal alpha 1- > 6D-glucose,…

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  Figure 2. Pathway analysis in peaks with multiple annotated metabolites. Pathways identified for the top 25 metabolites in each of the biomarker identification models. Square brackets indicate metabolites annotated to peaks including other metabolites; italics indicate that ≥1 annotated metabolite was connected to ≥1 different pathway. Arrows indicate metabolites increased (green upward arrow) or decreased (red downward arrow) in subjects with severe phenotypes compared with subjects with no or mild phenotypes. Asterisks denote the level of significance in Mann–Whitney U tests (* p < 0.05, ** p < 0.01, *** p < 0.001). Metabolites that did not associate with disease severity (p > 0.1) are indicated with an equals sign (“=”). Lists of annotated metabolites were condensed as in Figure 1.