Fig. 2: Unannotated splicing events in HD drive gene expression changes.
a, Bar plot showing rMATS splicing changes that are annotated (known) versus not annotated (novel). Bar plots showing MAJIQ and LeafCutter output for the detection of novel unannotated splicing events in the cortex and striatum from 3mos R6/2 and NT. b, Venn diagram showing MAJIQ junction overlap between TDP-43 KD changes from Šušnjar et al.73 versus R6/2 cortex and striatum samples. c, Heatmap showing exclusion and inclusion of novel unannotated splicing events in 3mos HD R6/2 versus NT (cortex and striatum). Gradient scale represents z-scores of normalized gene counts. d,e, Integrated Genomics Viewer99 sashimi plots of increased CE splicing in R6/2 (Cntn6; d) or loss of novel unannotated exon (UE) in NT (Ssbp2; e) in R6/2 and corresponding gene expression changes of the genes that contain the splicing event with statistical significance determined by unpaired two-tailed t-test (Cntn6: P < 0.0001, t = 7.111, degrees of freedom (d.f.) = 18, F = 1.612, 95% confidence interval (CI): 10.13–18.64; Ssbp2: P < 0.0001, t = 13.35, d.f. = 18, F = 6.684, 95% CI: −63.21 to −46.02). Data are presented as mean values ± s.e.m. n = 10 biological replicates per genotype (five males, five females). iCLIP-seq, individual-nucleotide resolution UV cross-linking and immunoprecipitation followed by high-throughput sequencing. f, Heatmap showing exclusion and inclusion of novel unannotated splicing events detected by MAJIQ in HD patient cortex compared to non-HD control from Al-Dalahmah et al.63 and corresponding gene expression changes of the genes that contain the splicing event. Gradient scale represents z-scores of normalized gene counts. CTRL, control.
