Fig. 4: Oncogenic structural variations drive transcriptional reprogramming through TAD remodeling in ccRCC.

a Comparative analysis of TAD fusion scores across distinct deletion classes. Boxplots depict distributions stratified by TAD deletion classes (boundary-spanning vs. internal deletions), with box ranges representing interquartile distances (IQR), central lines indicating medians, and whiskers extending to 1.5×IQR or extreme values within range. Statistical significance was determined by Wilcoxon rank-sum test. b Differential gene expression burden in SV hotspots. Stacked bars quantify proportions of differentially expressed genes (DEGs) in genomic regions stratified by TAD fusion score percentiles (top/bottom 50th percentile) versus genome-wide baselines across 786-O and OS-RC-2 cell lines. c Examples of the impact of inner TAD deletion frequency on the chromatin folding domain in OS-RC-2. Triangle heatmaps represent chromatin contact frequency, with the top showing OS-RC-2, middle showing HEK293T, and bottom showing the subtractive results. Histogram representing roadmap epigenome enhancer activity, marked by H3K27ac, in OS-RC-2 (red). d Examples of the impact of Cross TAD boundary deletion frequency on the chromatin folding domain in ccRCC. Triangle heatmaps represent chromatin contact frequency for 786-O (top), OS-RC-2 (second), HEK293T controls (third), with differential contact maps (fourth: 786-O vs control; fifth: OS-RC-2 vs control). Histograms show roadmap epigenome enhancer activity marked by H3K27ac in 786-O and OS-RC-2 (red). e Box plot of gene expression levels in regions with TAD fusion scores in the top 50%, bottom 50%, and genome-wide levels. The box spans the interquartile range (IQR), with the center line indicating the median and whiskers extending to 1.5×IQR (or the maximum/minimum values if within range). P values were calculated using the Wilcoxon rank-sum test.