Extended Data Fig. 6: Integration of eCLIP and KD–RNA-seq to identify splicing regulatory patterns.

a, Inner heatmap indicates the difference between normalized eCLIP read density at skipped exons that were excluded (left) or included (right) upon RBP knockdown, versus nSEs (as described in Supplementary Fig. 14). Out of 203 pairings of eCLIP and KD–RNA-seq in the same cell type (139 RBPs total), 92 pairings (72 RBPs) with at least 100 significantly included or excluded events are shown. Outer heatmap indicates positions at which the signal exceeds the 0.5–99.5% confidence interval obtained by 1,000 random samplings of the same number of events from the native skipped exon control set without multiple hypothesis testing correction. The number of RBP knockdown-altered skipped exons for each comparison is indicated. Data sets were hierarchically clustered at the RBP level, and data sets with fewer than 100 events are indicated by hatching. b, c, Heatmap indicates correlation (Pearson R) between splicing maps for knockdown-excluded (b) or knockdown-included (c) exons for RBPs profiled in both K562 and HepG2 cells, hierarchically clustered at the RBP level. d, Plot represents the distribution of Pearson correlations between splicing maps as shown in b, c, separated by whether the comparison is between the same RBP (n = 18 knockdown-included and 16 knockdown-excluded) or different RBPs (n = 612 knockdown-included and 480 knockdown-excluded comparisons, respectively) profiled in two cell types. Different RBPs are shown as smoothed histogram using a Normal kernel, and red line indicates mean. Significance was determined by two-sided Kolmogorov–Smirnov test.