Chromatin conformation capture with high-throughput sequencing (Hi-C) is a technique that measures the in vivo intensity of interactions between all pairs of loci in the genome. Most conventional analyses of Hi-C data focus on the detection of statistically significant interactions. However, an alternative strategy involves identifying significant changes in the interaction intensity (i.e., differential interactions) between two or more biological conditions. This is more statistically rigorous and may provide more biologically relevant results.