Here, we presented the scHiCDiff software tool that provides both nonparametric tests and parametirc models to detect differential chromatin interactions (DCIs) from single-cell Hi-C data. We thoroughly evaluated the scHiCDiff methods on both simulated and real data. Our results demonstrated that scHiCDiff, especially the zero-inflated negative binomial model option, can effectively detect reliable and consistent single-cell DCIs between two conditions, thereby facilitating the study of cell type-specific variations of chromatin structures at the single-cell level.

Availability and implementation

scHiCDiff is implemented in R and freely available at GitHub (

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