Abstract Chromatin loops form the hierarchical 3D genome architecture and act as critical regulatory hubs, bringing distant cis-elements together to precisely control target gene transcription. Disruption of these spatial interactions is closely linked to human diseases including cancer. Hi-C provides genome-wide interaction maps, yet robust identification of chromatin loops remains a major bottleneck in 3D genomics, especially for contact matrices with low signal-to-noise ratio and high sparsity.
