Monitoring heart transplant rejection by WGS of donor-derived cell free DNA

The Seattle Sequencing meetup welcomes Dr. Niklas Krumm, MD PhD, Lab Medicine Co-Chief Resident at the University of Washington who will review his development of a novel application of whole genome sequencing of cell free DNA.

Heart transplant rejection is a major cause of morbidity and mortality, and affects 15-20% of transplants in the first five years and current protocol includes 12 or more invasive biopsies of heart tissue in the first year alone. At the University of Washington Department of Laboratory Medicine, we are using whole genome sequencing to quantitate the level of donor-derived cell-free DNA (dd-cfDNA) as a non-invasive marker of acute allograft rejection for heart (and other solid organ) transplants. Our assay is based on a pairing low-coverage WGS from our existing clinical pipeline with SNP genotyping. Initial data shows that this approach provides rapid, cost-effective quantitation of dd-cfDNA, and has sufficient sensitivity and precision for monitoring renal and cardiac allograft rejection down to 0.1%. We are currently investigating parallel approaches, including tissue-of-origin and genotype-free approaches.