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CyclomicsSeq: targeted and genome-wide detection of circulating tumour DNA using nanopore consensus sequencing


Abstract

Levels of circulating tumour DNA (ctDNA) in liquid biopsies may serve as a sensitive biomarker for real-time, minimally-invasive tumour diagnostics and monitoring. To detect lowly abundant ctDNA molecules based on somatic variants, extremely sensitive sequencing methods are required. CyclomicsSeq enables consensus sequencing of concatenated copies of a single DNA molecule, increasing the base accuracy by ~60x and enabling accurate detection of, for example, TP53 mutations at frequencies down to 0.02%. A genome-wide version of CyclomicsSeq integrates multiple signals derived from ctDNA, including SNVs, CNVs, and fragmentation patterns, enabling monitoring of cancer with unprecedented dynamic range, and potentially paving the way for presymptomatic cancer screening.

Authors: Jeroen de Ridder

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