High-throughput conformation capture experiments, such as Hi-C provide genome-wide maps of chromatin interactions, enabling life scientists to investigate the role of the three-dimensional structure of genomes in gene regulation and other essential cellular functions. A fundamental problem in the analysis of Hi-C data is how to compare two contact maps derived from Hi-C experiments. Detecting similarities and differences between contact maps are critical in evaluating the reproducibility of replicate experiments and for identifying differential genomic regions with biological significance. Due to the complexity of chromatin conformations and the presence of technology-driven and sequence-specific biases, the comparative analysis of Hi-C data is analytically and computationally challenging.