Fig. 1: Alternative splicing analysis of SF3B1-mutated subset #2 CLL.

A ASE categories, including skipped exon (SE), alternative 3′ splice site usage (A3SS), alternative 5′ splice site usage (A5SS), mutually exclusive exon usage (MXE), and intron retention (RI). B Bar plot displaying numbers of all identified ASEs in the comparison of 18 SF3B1^MUT and 17 SF3B1^WT subset #2 cases across different ASE categories. 163,097 ASEs were detected and involved transcripts of 10,437 genes. C Volcano plot depicting all identified ASEs in the comparison of SF3B1^MUT and SF3B1^WT subset #2 cases. Red dots indicate ASEs that are considered significant (|ΔPSI | ≥ 20% and FDR ≤ 0.01; 80 ASEs). D Bar plot displaying numbers of significant ASEs in the comparison of SF3B1^MUT and SF3B1^WT subset #2 cases across different ASE categories. 80 ASEs were considered significant and involved transcripts of 62 genes. E Heatmap illustrating the individual PSI values for the 80 significant ASEs detected in the comparison of SF3B1^MUT and SF3B1^WT subset #2 cases. 33 ASEs occurred within the same gene at least twice. ASEs are displayed based on the ASE category. The bar plot to the right of the heatmap shows ΔPSI values. The gene affected by each ASE and the corresponding unique ASE ID are listed. Genes that encode ncBAF complex-interacting proteins are depicted in color. For multiple ASEs per gene, only the top ASE is colored, while the others are marked with black asterisks. Additional details of these ASEs are provided in Supplementary Table 3A, B. F Model of the ncBAF chromatin remodeling complex and previously reported ncBAF complex interactors. Alternatively spliced transcripts identified in SF3B1^MUT subset #2 CLL that encode ncBAF complex-related proteins are depicted in color. G Scattered box plot showing the PSI value distribution, ΔPSI values, and P values (Wilcoxon rank-sum test) for significant ncBAF complex-related ASEs identified in the comparison of SF3B1^MUT and SF3B1^WT subset #2 cases. The specific ASEs for ZEB1, BRD9, PLSCR1, TENT4B, CXXC1, DCAF16, UBP1, DLST, and SERBP1 have the unique ASE IDs ZEB1_SE_27141, BRD9_SE_53886, PLSCR1_SE_92684, PAPD5_SE_94061, CXXC1_SE_102397, DCAF16_SE_4627, UBP1_SE_85897, DLST_A3SS_2409, and SERBP1_A3SS_1321, respectively, in Supplementary Table 3A, B. The boxes represent the median and the interquartile range (IQR), while the whiskers extend to 1.5 times the IQR from the first and third quartiles. ASE: alternative splicing event; WT: wildtype; MUT: mutated; FDR: false discovery rate; PSI: percent spliced in; VAF: variant allele frequency.