A review of how the analysis of non-genetic features of DNA is expanding the utility of liquid biopsies is presented in Science this week. While liquid biopsies primarily focus on the detection of genetic markers in cell-free DNA (cfDNA), the use of DNA methylation, fragmentomic, and topologic analyses of circulating DNA are coming to the fore in clinical practice, according to a trio of scientists from the Chinese University of Hong Kong. The researchers discuss advances in the field and highlight the need for new detection methods for nongenetic markers for liquid biopsies that can be more easily implemented on a large scale. They also call for liquid biopsy research to expand beyond plasma into additional biofluids, as well as for the exploration of the biological interactions between the processes underpinning emergent markers. Doing so, the authors write, will require significant investment in basic research in liquid biopsies since much of the focus currently rests on clinical translation and commercial exploitation.
A genome-wide CRISPR-Cas9 screen reveals new details about the relationships between the enzymes involved in DNA methylation, according to a study in this week's Science. A team led by investigators from the Sloan Kettering Institute use a knock-in DNA methylation reporter to perform the screen in human embryonic stem cells and identify an uncharacterized gene, called QSER1, that safeguards bivalent promoters and poised enhancers of developmental genes, especially those in DNA methylation valleys, against hypermethylation. They also show that QSER1 works with TET1 to guard transcriptional and developmental programs from DNMT3-mediated de novo methylation at important genomic loci.