Figure 1
GCG expression associates with changes in the expression of AGER and its correlated genes in the islets of type 1 diabetes donors. (A) Volcano plot of AGER and genes correlated with AGER at Pearson's r = 0.99, 0.999, 0.9999, 0.99999–1.0. Significant differences for control, non-diabetic autoantibody-positive and type 1 diabetes donors combined (n = 50; top row), and within the type 1 diabetes cohort alone (n = 20; bottom row). Blue dots are significant changes, red dots are significant changes within type 1 diabetes group. See Table S1–S4 for differentially expressed gene lists. No differences were seen within the control or non-diabetic autoantibody-positive groups. Significance was defined by FDR q < 0.05, fold-change > 2.0. Where multiple probes detected changes in the expression of one gene (inset rainbow bars, right axes), the probe with the greatest mean expression is shown. (B) Unsupervised hierarchically clustered heat maps for differentially expressed genes in type 1 diabetes, which were correlated with AGER expression (r = 0.99–1.0). Row annotations, GCGhi and GCGlo subgroups within type 1 diabetes cohort. Column annotations, Gene Ontology enrichment and overrepresentation (Bonferroni adjusted p < 0.05). See Figs. S2–S3 for Gene Set Enrichment Analysis (GSEA). (C,D) Random forest model trained on 60% (12 of 20) type 1 diabetes donors, then validated on the remaining 40% (8 of 20) type 1 diabetes donors. (C) ROC curve for classification into GCGhi or GCGlo in validation cohort. (D) Variable importance by mean decrease in accuracy.
