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An important unanswered question in chromatin biology is the extent to which long-range looping interactions change across developmental models, genetic perturbations, drug treatments, and disease states. Computational tools for rigorous assessment of cell type-specific loops across multiple biological conditions are needed. We present 3DeFDR, a simple and effective statistical tool for classifying dynamic loops across biological conditions from Chromosome-Conformation-Capture-Carbon-Copy (5C) and Hi-C data. Our work provides a statist