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Billy Lau

NCM 2022: Single molecule methylation profiles of cell-free DNA in cancer with nanopore sequencing

Epigenetic characterization of cell-free DNA (cfDNA) is an emerging approach for detecting and characterizing diseases such as cancer. We developed a strategy using nanopore-based, single-molecule sequencing to measure cfDNA methylomes. This approach generated up to hundreds of millions of reads per cfDNA sample using research samples obtained from cancer patients, which is an order of magnitude improvement over existing nanopore sequencing methods. We developed a single-molecule classifier to determine whether individual reads originated from a tumour or immune cells. Leveraging methylomes of matched tumours and immune cells, we characterized cfDNA methylomes in research samples from cancer patients and demonstrate the potential of using this for longitudinal monitoring during treatment.