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