Supplementary Figure 5: Characteristics of differential Hi-C and Capture-C contacts.

a-b, Top: positional distribution of differential Hi-C (a) or Capture-C (b) contacts originating from Transcription Start Sites (TSSs) of differentially expressed genes (DE-genes) with >1.5 fold change in expression (orange) and non-differentially expressed (non-DE, grey) genes. Genes are aligned by their TSS and transcribed to the right. 95% confidence bands (shaded ribbons) estimated using bootstrapping. Bottom right: heatmap of differential contacts (balancer/wild-type, log₂ fold change) for 200 randomly sampled DE-genes (Hi-C) (a) or for all captured DE-genes (Capture C) (b). Bottom left: expression change (log₂ fold change) for genes shown in the heatmap. c, Fraction of Hi-C (left) and Capture-C (right) differential contacts originating from different classes and having their other end overlapping a promoter of a differentially expressed or non-differentially expressed gene, a distal enhancer or a distal DHS. The observed fraction (purple) is compared to the distribution obtained from random shuffling (1,000 times) of differential contacts (grey). Center line, median; box limits, upper and lower quartiles; whiskers, 1.5x interquartile range. p-values (two-sided permutation test) of significant differences (p<0.05) are indicated. Numbers in parentheses indicate: number of differential contacts in the given class, and (if applicable) number of unique genes, DE-genes or non-DE genes on the viewpoint side. d, Correlation of change in expression (log₂ fold change) between pairs of DE-genes linked by a differential contact. Concordant gene expression (14 cases) in green, discordant (4 cases) in purple. Pearson correlation coefficient (r) indicated. e, Strength of all differential Capture-C contacts (balancer/wild-type, log₂ fold change) established from each Capture-C probe region, ordered (left to right) based on the change in expression (log₂ fold change) of the most DE gene assigned to the probe. Note that strongly differentially expressed genes (to the left and right of the purple arrows) do not have more, or stronger, differential Capture-C contacts.