DE NOVO CHARACTERIZATION OF CELL-FREE DNA FRAGMENTATION HOTSPOTS IN HEALTHY AND EARLY-STAGE CANCERS

摘要

A system and method for identifying genomic regions with higher fragmentation rates than the local and global backgrounds as part of diagnosing early stage cancer is provided. The method includes steps of: de-novo characterizing genome-wide cell-free DNA fragmentation regions with higher fragmentation rates than the local and global backgrounds from whole-genome sequencing by weighing the fragment coverages in each region by a ratio of average fragment sizes in the region versus that in the whole chromosome to generate a score; and identifying DNA fragmentation regions of interest based upon comparing the score with a threshold. The system and method can utilize identified DNA fragmentation hotspots for the detection and localization of multiple early-stage cancers (or certain other non-malignant disease).