Short fragments of cell-free DNA (cfDNA) that circulate in blood, urine, and other biofluids can offer an information-rich window into human physiology and disease. By looking at the methylation markers of cfDNA, researchers can identify the tissue from which the DNA came. A new study used this method to monitor infectious and immune-related diseases, including COVID-19 infection, and demonstrate the potential clinical applications of this technology. Alexandre Cheng, BSc, a doctoral student in biomedical engineering at Cornell University, presented the results of the study at the American Society of Human Genetics 2020 Virtual Meeting (October 27-30) (https://www.ashg.org/meetings/2020meeting/). cfDNA tests have already impacted clinical patient care. For example, non-invasive prenatal testing uses cfDNA to screen for anatomic or physiological problems with the fetus and multiple clinical trials are underway to evaluate cfDNA for monitoring transplant rejection. Originating from dead cells, cfDNA is ubiquitous in bodily fluids. During infection or immune-related diseases that cause tissue damage, one would expect to see an increased amount of cfDNA from the attacked tissue. To identify tissues-of-origin of cfDNA, Mr. Cheng and his colleagues analyzed the methylation markers of DNA, which are tissue-specific, through a process called whole-genome bisulfite sequencing. The researchers performed this process on cfDNA from the biofluids of various patients to screen for tissue damage in three different disease settings. In an exciting and currently relevant application, the researchers sequenced plasma-derived cfDNA from COVID-19 patients. They observed high initial lung- and liver-derived cfDNA, which decreased as patients recovered, but also significant increases of erythroblast cfDNA.
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