Loading...
Nanopore-based consensus sequencing enables accurate multimodal tumor cell-free DNA profiling
Chen, L. T. Jager, M. Rebergen, D. Brink, G. J. van den Ende, T. Vanderlinden, W. Kolbeck, P. Pagès-Gallego, M. van der Pol, Y. Besselink, N.
Chen, L. T.
Jager, M.
Rebergen, D.
Brink, G. J.
van den Ende, T.
Vanderlinden, W.
Kolbeck, P.
Pagès-Gallego, M.
van der Pol, Y.
Besselink, N.
Abstract
Shallow genome-wide cell-free DNA sequencing holds great promise for noninvasive cancer monitoring by providing reliable copy number alteration (CNA) and fragmentomic profiles. Single-nucleotide variations (SNVs) are, however, much harder to identify with low sequencing depth due to sequencing errors. Here, we present Nanopore Rolling Circle Amplification (RCA)-enhanced Consensus Sequencing (NanoRCS), which leverages RCA and consensus calling based on genome-wide long-read nanopore sequencing to enable simultaneous multimodal tumor fraction (TF) estimation through SNVs, CNAs, and fragmentomics. The efficacy of NanoRCS is tested on 18 cancer patient samples and seven healthy controls, demonstrating its ability to reliably detect TFs as low as 0.24%. In vitro experiments confirm that SNV measurements are essential for detecting TFs below 3%. NanoRCS provides an opportunity for cost-effective and rapid sample processing, which aligns well with clinical needs, particularly in settings where quick and accurate cancer monitoring is essential for personalized treatment strategies.
Description
Date
2025
Publisher
Collections
Files
Loading...
Found from Unpaywall
Adobe PDF, 11.59 MB
Keywords
Type
Article
Citation
Chen LT, Jager M, Rebergen D, Brink GJ, van den Ende T, Vanderlinden W, et al. Nanopore-based consensus sequencing enables accurate multimodal tumor cell-free DNA profiling. Genome Res. 2025 Apr 14;35(4):886-99. PubMed PMID: 39805703. Pubmed Central PMCID: PMC12047234. Epub 2025/01/14. eng.