Detecting cell-of-origin and cancer-specific methylation features of cell-free DNA from Nanopore sequencing

Efrat Katsman; Shari Orlanski; Filippo Martignano; Ilana Fox-Fisher; Ruth Shemer; Yuval Dor; Aviad Zick; Amir Eden; Iacopo Petrini; Silvestro G Conticello; Benjamin P Berman

doi:10.1186/s13059-022-02710-1

Detecting cell-of-origin and cancer-specific methylation features of cell-free DNA from Nanopore sequencing

Genome Biol. 2022 Jul 15;23(1):158. doi: 10.1186/s13059-022-02710-1.

Authors

Efrat Katsman^#¹, Shari Orlanski^#¹, Filippo Martignano^#², Ilana Fox-Fisher¹, Ruth Shemer¹, Yuval Dor¹, Aviad Zick³, Amir Eden⁴, Iacopo Petrini⁵, Silvestro G Conticello^#^{6

7}, Benjamin P Berman^#⁸

Affiliations

¹ Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
² Core Research Laboratory, ISPRO, Florence, Italy.
³ Department of Oncology, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.
⁴ Department of Cell and Developmental Biology, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.
⁵ Unit of Respiratory Medicine, Department of Critical Area and Surgical, Medical and Molecular Pathology, University Hospital of Pisa, Pisa, Italy.
⁶ Core Research Laboratory, ISPRO, Florence, Italy. silvestro.conticello@cnr.it.
⁷ Institute of Clinical Physiology, National Research Council, Pisa, Italy. silvestro.conticello@cnr.it.
⁸ Department of Developmental Biology and Cancer Research, Institute for Medical Research Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel. ben.berman@mail.huji.ac.il.

^# Contributed equally.

Abstract

The Oxford Nanopore (ONT) platform provides portable and rapid genome sequencing, and its ability to natively profile DNA methylation without complex sample processing is attractive for point-of-care real-time sequencing. We recently demonstrated ONT shallow whole-genome sequencing to detect copy number alterations (CNAs) from the circulating tumor DNA (ctDNA) of cancer patients. Here, we show that cell type and cancer-specific methylation changes can also be detected, as well as cancer-associated fragmentation signatures. This feasibility study suggests that ONT shallow WGS could be a powerful tool for liquid biopsy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cell-Free Nucleic Acids*
Circulating Tumor DNA*
DNA Methylation
High-Throughput Nucleotide Sequencing
Humans
Nanopore Sequencing*
Neoplasms* / genetics

Substances

Cell-Free Nucleic Acids
Circulating Tumor DNA