Haplotype-resolved, multi-modal, tumour-normal analysis of cancer genomes using nanopore sequencing
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Here we demonstrate how Oxford Nanopore native long-read sequencing enables the direct detection of not only SNVs, but also break point-resolved simple and complex structural variants (SVs and CNVs), haplotype phasing of all variant types, and identification of DNA modifications like 5-methylcytosine (5mC) and 5-hydroxy-methylcytosine (5hmC) from a single tumour-normal dataset.
We use well characterised cancer cell lines and in silico benchmarking datasets to assess somatic SNV, and SV calling performance using different sequencing depths, and also demonstrate how long nanopore reads enable haplotype and clone specific CNV calling. Finally, we use twelve matched tumour-normal pairs from four different tissues to showcase a comprehensive tumour-normal analysis using Nanopore sequencing.