Definition of CIS, BCP and z-threshold hot-spot methods. (A) The CIS hot-spot definition implemented here is based on a commonly used density metric [19, 21]. (B) Our 'z-threshold' and 'BCP' hot-spot definitions operate on a partition of the genome into 1 Mb bins. The number of VIS per megabase bin is tallied and then converted to a z-score by subtracting the mean and dividing by the standard error, calculated across all bins. Bins with high z-scores are called 'hot-bins'. Hot-spots are defined by grouping consecutive hot-bins and setting each external boundary to the closest VIS.