Single-molecule methylation profiles of cell-free DNA in cancer with nanopore sequencing
Billy T. Lau, Alison Almeda, Marie Schauer, Madeline McNamara, Xiangqi Bai, Qingxi Meng, Mira A. Partha, Susan M. Grimes, HoJoon Lee, Gregory M. Heestand, Hanlee P. Ji
Abstract
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 200 million reads for a single cfDNA sample from cancer patients, an order of magnitude improvement over existing nanopore sequencing methods. We developed a single-molecule classifier to determine whether individual reads originated from a tumor or immune cells. Leveraging methylomes of matched tumors and immune cells, we characterized cfDNA methylomes of cancer patients for longitudinal monitoring during treatment.