FreeHi-C: high fidelity Hi-C data simulation for benchmarking and data augmentation

Ability to simulate realistic high-throughput chromatin conformation (Hi-C) data is foundational for developing and benchmarking statistical and computational methods for Hi-C data analysis. We propose FreeHi-C, a data-driven Hi-C simulator for simulating and augmenting Hi-C datasets. FreeHi-C employs a non-parametric strategy for estimating interaction distribution of genome fragments from a given sample and simulates Hi-C reads from interacting fragments. Data from FreeHi-C exhibit higher fidelity to the biological Hi-C data compared with other tools in its class. FreeHi-C not only enables benchmarking a wide range of Hi-C analysis methods but also boosts the precision and power of differential chromatin interaction detection methods while preserving false discovery rate control through data augmentation.