Chromatin and Nucleosome-Associated Features in Liquid Biopsy: Implications for Cancer Biomarker Discovery

Cell-free DNA (cfDNA) from the bloodstream has been studied for cancer biomarker discovery, and chromatin-derived epigenetic features have come into the spotlight for their potential to expand clinical applications. Methylation, fragmentation, and nucleosome positioning patterns of cfDNA have previously been shown to reveal epigenomic and inferred transcriptomic information. More recently, histone modifications have emerged as a tool to further identify tumor-specific chromatin variants in plasma. A number of sequencing methods have been developed to analyze these epigenetic markers, offering new insights into tumor biology. Features within the cfDNA allow for cancer detection, subtype and tissue of origin classification, inference of gene expression, and improve the differentiation of cancer status and types. These methods provide insights into uncovering the complexity of cancer genetics and the dynamic nature of its progression. In this review, we highlight the array of features that can be extracted from chromatin- and nucleosome-associated organization for cancer classification.