(a) Examples of events amongst the 100-most correlated to insolubility, with Leafcutter (LC) PSI plotted on the X-axis and insolubility (%) on the Y-axis. DS events are shown for the following genes (clockwise, from upper left): BBS2, GABRG2, HNRNPA3, HNRNPH1, RIOK3 and CCDC136 (events listed in Supplementary file 1C). (b) Heatmap of 100 events most correlated/anti-correlated (absolute value Spearman coefficient) with hnRNP H insolubility. Blue-red color scale represents Z-score for normalized PSI. Four rows above heatmap display whether each sample was included in the groupings used for the identification of DS events, termed 'In analysis' (black = yes, white = no), gender (pink = female, blue = male), Patient subtype (see key), and percent insolubility hnRNP H (180,000 x G), ranging from light (low insolubility) to dark (high insolubility) gray. Yellow is shown for cases without insolubility data. Patients are arranged by subtype, with increasing insolubility from left to right, where data is available. (c) Gene set enrichment analysis of top 200 dysregulated splicing events correlated to hnRNP H insolubility. (d) Heatmap of significant DS events that occur in a set of common splicing factor genes, simplified to the single most changed event per gene (hnRNPs, SR proteins, ALS-related RBPs or SMN; events listed in Supplementary file 1D). The same four rows apply as in (b). (e) Bar graph depicting that patients like-C9 are 3.8-times more likely to have symptoms of FTD than patients like-control (Fisher’s exact test, Odds ratio (OR) = 3.8, p=0.032).