Fragmentation patterns of cell-free DNA reflect the chromatin structure of the cells from which these fragments are derived. With whole-genome sequencing of liquid biopsies and suitable bioinformatic methods, it is thus possible to assess cell-of-origin and epigenetic cell states in a minimally
invasive manner. LIQUORICE is a user-friendly software tool that makes such analyses broadly and easily available. The tool takes aligned whole-genome sequencing data as input and calculates bias-corrected coverage signatures for pre-defined genomic region sets. By providing user-defined sets of regions with tissue-specific or tumor-specific open chromatin, LIQUORICE can be used for a wide range of detection, classification, and quantification tasks in the analysis of liquid biopsies. LIQUORICE is freely and openly available as a Python package and command-line tool for UNIX-based systems from bioconda.