Fast Low-Input Efficient Hi-C

We developed FLIE (Fast Low-Input Efficient) Hi-C, a highly optimized and simplified Hi-C variant. Our method shortens the duration of Hi-C from five days to two days and decreases key reagent amounts 5-20 fold, while maintaining experimental controls and data quality. Importantly, the method also reduces the required input material by 100-1000 fold, as we demonstrate by generating detailed high complexity interaction maps from low-input sorted mouse frozen neuron nuclei and from 5,000-10,000 human Hap1 cells.