Extended Data Fig. 6: Models for activation in engineered rearrangements.

a, Example plot showing method for calculating ABC score for MYC with rearranged partner sites. Interaction frequency between the MYC promoter and H3K27ac peaks in the partner region (“contact”) is multiplied by the strength of the H3K27ac signal (“activity”) at each peak across the partner region to obtain a final score for each peak. This signal is then summed across all peaks over the partner region. Of note, this example plot only shows the calculations for the six strongest H3K27ac peaks in the partner region, whereas the actual score is calculated using all H3K27ac peaks. b, Receiver Operating Characteristic (ROC) curve for the TAD delimited ABC model. Shown above the plot is the area under the curve (AUC). c, ROC curve for an ABC model where contacts are measured from genome wide average interaction frequencies. d, Plots showing ABC scores for genes neighboring MYC. Above the plot is the Pearson correlation coefficient for each gene between the genes’ ABC score and expression. e, Heat map of the TAD surrounding MYC as well as the location and relative position of the genes shown in panel D. f, Scatter plot showing ABC scores and summed enhancer activity within 3 Mb for every gene in 30 cancer cell lines. g, Scatter plot showing ABC scores and summed interaction within 3 Mb for every gene in 30 cancer cell lines. h, The number of enhancers per gene linked by the marginal ABC score >= 0.1 for ABC-correlated and non-correlated genes. Gray lines show the paired values for each cell line comparing ABC-correlated and non-correlated genes. P-value is from paired Wilcoxon test. i, Percentage of ABC responsive (blue) and protein-coding genes classified as transcription factors. Protein coding genes are from the Gencode reference annotation. P-value is from Fisher’s Exact test. j, Percentage of ABC responsive (blue) and protein-coding genes classified as oncogenes according to the Cosmic cancer gene census. P-value is from Fisher’s Exact test. k, Normalized interaction frequency as a function of distance for Hi-C interactions at 10 kb resolution in SK-N-DZ cells. Interaction frequency decays exponentially as a function of distance. l, Enhancer activity based on H3K27ac ChIP-seq as quantified by the ROSE super enhancer calling activity for all enhancers in SK-N-DZ cells. Enhancers are displayed ranked according to strength. Super-enhancers show exponentially stronger enhancer activity compared with typical enhancers. m, Enhancer activity required to achieve the equivalent activity-by-contact score for the median enhancer at 20 kb in SK-N-DZ cells as a function of genomic distance. Shown as a dashed line is the minimal enhancer strength categorized as a “super-enhancer” in SK-N-DZ cells by the ROSE algorithm. Due to the exponential decay in interaction frequency. After ~300 kb, the only enhancers capable of producing an ABC score equivalent to the median enhancer at 20 kb are super enhancers.