Stephanie Yu from The Chinese University of Hong Kong in China presented at the Nanopore Community Meeting in Singapore (2023) on “Long cell-free DNA: the beginning of a new era in liquid biopsy.” Cell-free DNA is released into circulation after cell lysis. Their group is interested in novel molecular diagnostics based on cell-free DNA in plasma. They are focusing on DNA that is fragmented and circulating in plasma. Short-read sequencing has revealed patterns in fragmentation resembling DNA wrapped around nucleosomes and histones. The team believed that long cell-free DNA was there. Yu and team wanted to explore cell-free DNA in maternal plasma using long-read DNA sequencing. They identified differences in cell-free DNA. Yu and team found fetal DNA in maternal plasma. Using computer simulations, the team estimated the percentage of cell-free DNA fragments with informative SNPs. Longer DNA was predicted to have more cell-free DNA. Methylation levels could then be used to determine the origin of the DNA. The team found reduced percentages of long cfDNA. The team wants to learn from cfDNA patterns and sequences to detect cancer and improve their algorithms. They are now able to do tissue-of-origin analysis. The team believes that long-read sequencing has allowed them to analyze a population of DNA circulating that is useful in cancer and other detection systems. Performance is being tested and improve. This area of research and its methods is growing.
