Plasma cell-free DNA (cfDNA) are small molecules generated through a non-random fragmentation procedure. Despite commendable translational values in cancer liquid biopsy, however, the biology of cfDNA, especially the principles of cfDNA fragmentation, remains largely elusive. Through orientation-aware analyses of cfDNA fragmentation patterns against the nucleosome structure and integration with multidimensional functional genomics data, here we report a DNA methylation – nuclease preference – cutting end – size distribution axis, demonstrating the role of DNA methylation as a functional molecular regulator of cfDNA fragmentation. Hence, low-level DNA methylation could increase nucleosome accessibility and alter the cutting activities of nucleases during DNA fragmentation, which further leads to variation in cutting sites and size distribution of cfDNA. We further develop a cfDNA ending preference-based metric for cancer diagnosis, whose performance has been validated by multiple pan-cancer datasets. Our work sheds light on the molecular basis of cfDNA fragmentation towards broader applications in cancer liquid biopsy.

Brain cancers are among the top causes of death worldwide. Although, the survival rates vary widely depending on the type of the tumor, early diagnosis could generally benefit in better prognosis outcomes of the brain cancer patients. Conventionally, neuroimaging and biopsy are the most widely used approaches in diagnosis, subtyping, and prognosis monitoring of brain cancers, while emerging liquid biopsy assays using peripheral blood or cerebrospinal fluid have demonstrated many favorable characteristics in this task, especially due to their minimally invasive and easiness in sampling nature. Here, we review the recent studies in the liquid biopsy of brain cancers. We discuss the methodologies and performances of various assays on diagnosis, tumor subtyping, relapse prediction as well as prognosis monitoring in brain cancers, which approaches have made a big step toward clinical benefits of brain cancer patients.

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Light plays an important role in many plant biological processes such as photosynthesis and photomorphogenesis. In this study, we applied RNA-seq, ATAC-seq and ChIP-seq to study transcriptional regulation at multiple levels in Brachypodium distachyon (B. distachyon) under controlled light and extended darkness conditions. We have identified 8,400 differentially expressed genes (DEGs), and they are enriched in photosynthesis Gene Ontology terms. ATAC-seq signal decreased after extended darkness, indicating that light has a genome-wide impact on chromatin accessibility. We also found that differential H3K4me3 and H3K9ac modifications are enriched in gene loci associated with photosynthesis and other light-dependent reactions. Finally, ChIP-seq revealed that a HY5-Like transcription factor could directly bind to the promoter open chromatin regions of these light reaction genes. Taken together, our results indicated the dynamic transcriptional reprograming associated with light-dark changes in Brachypodium could be resulted from the combinatorial action of multiple epigenetic features.