Whole-genome Nanopore sequencing to identify cell of origin and cancer-specific changes from cell-free DNA

Berman Benjamin, HUJI, School of Medicine - IMRIC, Developmental Biology and Cancer Research



Life Sciences and Biotechnology   


DNA sequencing, tumor detection, bioinformatic technology


DNA methylation (5mC) is among the most promising biomarkers for detecting cancer and other diseases using cell-free DNA (cfDNA) from blood (liquid biopsy). The most popular technique for detecting 5mC involves sodium bisulfite treatment, which destroys and fragments DNA. This is problematic when the amount of disease-associated DNA is only a small fraction of all cell-free DNA in the blood. Bisulfite treatment also removes fragmentation patterns which can be used in conjunction with 5mC to detect cell of origin and cancer-specific changes. Other non-bisulfite approaches for cfDNA involve complex sample processing steps such as enzymatic treatment or antibody pulldown. Current methods require more than a day of sequencing time and is often not available on site at most clinical institutions.

Our innovation Nanopore shallow whole-genome sequencing (cfNano) is a new approach that can detect both cell of origin and cancer-specific features of cfDNA from a combined profile of copy number alterations, 5mC, and fragmentomics. It can also potentially detect other non-cancer conditions such as myocardial infarction, sepsis, and acute pancreatitis. The accessible and rapid nature of Nanopore sequencing make it an attractive platform for cfDNA-based diagnostics.

On both technological and functional sides, Nanopore sequencing is distinguished by:

  • Accessible technology: Oxford Nanopore Technologies (ONT) sequencers have negligible equipment costs, a small footprint that can be used in any institution or in the field
  • Rapid test: that opens up new possibilities for urgent care and emergency medicine
  • Proven efficiency: for classification of cancer types

Illumina-based sequencing approaches are currently being combined with bisulfite, enzymatic, or immunoprecipitation-based sample processing for cancer detection. These involve complex sample processing and waiting for Illumina sequencing core or service providers to process them. Our technology obtains the same information using the Nanopore platform, which is simple and rapid to use. In the future, cfNano may prove superior in accuracy, because we retain the original cell type proportions and fragmentomic patterns which can get distorted by bisulfite treatment and PCR amplification. Our application is the first successful Nanopore technology to identify cfDNA cell of origin.

The expected outcome is a blood test which could detect cancer and monitor changes in cancer DNA during progression or treatment. Our tool could be used by the health professionals’ market, such as liquid biopsy diagnostic companies, Hospital clinical labs and Oncology departments or community clinics. By adopting this innovative tool, they could offer a higher cancer detection rate and accuracy than in other institutes and gain a competitive advantage. We also envision applications in emergency medicine, since DNA methylation sequencing has successfully been used to detect sepsis, pancreatitis, myocardial infarction and other acute coronary syndromes. The rapid nature of ONT sequencing could be of a distinct clinical advantage here.


Contact for more information:

Ariela Markel
VP, Business Development, Healthcare
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