FreeHi-C simulates high-fidelity Hi-C data for benchmarking and data augmentation

The ability to simulate high-throughput chromatin conformation (Hi-C) data is foundational for benchmarking Hi-C data analysis methods. Here we present a nonparametric strategy named FreeHi-C to simulate Hi-C data from the interacting genome fragments. Data from FreeHi-C exhibit high fidelity to biological Hi-C data. FreeHi-C boosts the precision and power of differential chromatin interaction detection through data augmentation under preserved false discovery rate control. FreeHi-C takes Hi-C sequencing data as input and simulates reads with random mutations and indels from the interacting fragment pairs. FreeHi-C-simulated replicates are used for benchmarking Hi-C analysis methods and enable data augmentation for differential chromatin interaction analysis.