Figure 4.

CDM subcohorts display variable alternative splicing dysregulation compared with age-matched pediatric controls in the presence of large CTG repeat expansions. (A) UpSet plot displaying number of shared skipped exon (SE) events shared between all four CDM subcohorts (CDM_Group versus age-matched PeCo |ΔΨ| ≥ 0.1, FDR ≤ 0.05) as outlined in associated table. Each column corresponds to a CDM group or set of CDM groups (dots connected by lines below x-axis) sharing the same events. The first four columns represent the number of SE events dysregulated in each subcohort compared with age-matched controls and are colored accordingly. All other columns highlighting shared events are shown in gray. The number of SE events in each set is shown above the column. The total number of dysregulated SEs within each CDM subcohort is displayed in a separate bar plot in the bottom left. (B) Number of SE events identified as dysregulated within each CDM subcohort when compared with age-matched PeCos as outlined in (A) upon increase in threshold for IΔΨI. (C) Area-proportional Venn diagram displaying overlapping SE events mis-spliced in select CDM subcohorts (CDM_Group versus age-matched PeCo |ΔΨ| ≥ 0.1, FDR ≤ 0.05). (D) Scatter plot of Ψ for 392 SE events only dysregulated in CDM_adolescent-2 and CDM_infantgroups. Events differentially spliced (|ΔΨ| ≥ 0.2) are colored in red. (E) Scatter plot of CDM individuals’ CTG repeat expansion size versus age at biopsy. Pearson correlation is shown. Individuals with repeat biopsies were only plotted once and colored according to the assigned CDM cohort at first biopsy. (F) Mean CTG repeat length for CDM subcohorts. (CTG)_n was only available for some individuals. Repeat length for individuals with repeat biopsies was only utilized for age and CDM group assigned at first biopsy. Data represented as mean ± standard deviation, ^*P < 0.05, one-way ANOVA, Tukey’s post-hoc test. All unannotated comparisons were not significant.