Fig. 3

Genes that demonstrated differential transcript usage in ALS patients relative to controls. (a) Overlap of ALS-control differential transcript usage events between the five examined brain regions. In the upset plot the brain regions involved in each intersection are indicated by a filled dot. Significant differential transcript usage events were defined as those with FDR < 0.05 and ≥ 10% change in isoform usage between ALS patients and controls. (b) Differential transcript usage of the canonical FSTL3 transcript was detected in four brain regions. Top panel: Visual depiction of the FSTL3 transcripts that contributed ≥ 5% of total gene expression in at least one brain region. Predicted Kazal_1 and Kazal_2 domains overlap at blue arrow. Bottom panel: Comparison of isoform fractions between ALS patients and controls for each of the four FSTL3 transcripts. Significant differences (q-value < 0.05) are indicated by an asterisk. Significant differential transcript usage between ALS patients and controls of two isoforms was detected for (c)POLDIP3 in the cerebellum and (d)XBP1 in the motor cortex. Left panels: Visual depiction of the transcripts that contributed ≥ 5% of total gene expression. Turquoise transcripts are “protein_coding” and maroon transcript is “retained_intron”. The yellow shading behind transcripts highlights the exonic regions that differ between the two significant differentially used transcripts. Right panels: Comparison of isoform fractions between ALS patients and controls. Significant differences (q-value < 0.05) are indicated by an asterisk. gDTUs, genes with differential transcript usage