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Nanopore-based consensus sequencing enables accurate multimodal tumour cell-free DNA profiling


Chen et al. explored the potential of nanopore rolling circle amplification (RCA)-enhanced consensus sequencing (NanoRCS) for detecting cell-free tumour DNA. NanoRCS simultaneously identified SNVs, copy number alterations (CNAs), and fragmentomics patterns. With results in 20–110 minutes and lower error rates than short-read sequencing approaches, this non-invasive method could facilitate real-time cancer monitoring in the future.

Key points:

  • NanoRCS reliably detected tumour fractions as low as 0.24%.

  • The authors reported low SNV error rates (0.00072 for NanoRCS consensus-called reads, 0.00674 for Oxford Nanopore non-consensus-called reads, and 0.00108 for short-read sequencing technology after error correction in overlapping regions of paired-end reads).

  • NanoRCS provided real-time results, detecting tumour-specific SNVs within 20–110 minutes of sequencing.

  • The method demonstrated utility for oesophageal, ovarian, and granulosa cell cancers.

  • By leveraging Oxford Nanopore sequencing, NanoRCS offers a low-cost, portable alternative to other sequencing platforms, with faster turnaround and smaller batch compatibility.

Sample type: human cell-free DNA from blood plasma or ascites

Authors: Li-Ting Chen, Myrthe Jager, Dàmi Rebergen, Geertruid J. Brink, Tom van den Ende, Willem Vanderlinden, Pauline Kolbeck, Marc Pagès-Gallego, Ymke van der Pol, Nicolle Besselink, Norbert Moldovan, Nizar Hami, Wigard Kloosterman, Hanneke van Laarhoven, Florent Mouliere, Ronald Zweemer, Jan Lipfert, Sarah Derks, Alessio Marcozzi, Jeroen de Ridder

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