Circulating cell-free DNA. Short fragments of cell-free DNA circulate in blood, urine and other biofluids and offer an information-rich window into human physiology, with rapidly expanding applications in prenatal testing, cancer screening, organ transplant monitoring and infectious disease testing.
Our research pursues technologies and applications of cell-free DNA in infectious and immune-related disease. The great promise of cfDNA in diagnostic medicine derives from i) its abundance: 10-100 billion molecules of cell-free DNA can be isolated from just 1 mL of plasma. The combined DNA sequence of these molecules is sufficient to cover the human genome 1,000 to 10,000 fold. ii) Its origin: cell-free DNA is derived from dead cells and comprises rich information about cells in the blood and any vascularized tissue that can be accessed noninvasively. iii) Its short lifetime: cell-free DNA is cleared from the blood within 60 minutes. cell-free DNA therefore provides a very dynamic window into health.
Our recent research in this area has led to i) novel molecular and bioinformatic technologies to obtain and mine sequence information from cell-free DNA, and ii) novel applications of cell-free DNA in diagnostic medicine:
- We have demonstrated that a single-stranded DNA library preparation uncovers the diversity of ultrashort cfDNA in plasma.
- We have reported that urinary cell-free DNA is a versatile analyte for the diagnosis of urinary tract infection
- We have developed a cell-free DNA metagenomic sequencing assay that integrates the damage response to infection.
- We have reported how cell-free DNA tissues-of-origin profiling can be used to predict Graft versus Host Disease and detect infection after hematopoietic cell transplantation
- We have created a bioinformatics tool to screen for infection from low-biomass isolates of cell-free DNA