A versatile computational pipeline for the preprocessing of cell-free DNA fragmentation data

Cell-free DNA (cfDNA) emerges as a promising liquid biopsy biomarker for cancer diagnosis and patient monitoring. Complementing mutation-based assays, cfDNA carries information about epigenetic modifications from decaying cells. This information is encoded in the shape of the cfDNA fragments. Specifically, fragments from cancer tend to be shorter than those originating from other adult cells, enabling a distinction between cancer patients and healthy individuals. Additional cfDNA features such as fragment end motifs and information on nucleosome positioning provide further insight into cancer biology. These cfDNA measures are typically inferred from low-pass whole genome sequencing and subsequent bioinformatics processing. A key bioinformatics step is the alignment of DNA sequencing reads to the reference genome, which critically depends on preprocessing steps such as read trimming and