Comparison of structural variant calls from Oxford Nanopore haplotype-resolved and telomere-to-telomere genome assemblies

Structural variants (SVs), including insertions and deletions larger than 50 bp, duplications, inversions, and translocations, represent a major source of genetic variation in human populations. These variants have historically been difficult to detect with array and short-read-based approaches, however, hindering efforts to understand their importance in human health and disease.

Modern long-read sequencing technologies have drastically improved our ability to identify and characterise SVs, recently culminating in complete 'telomere-to-telomere' (T2T) de novo genome assemblies which can represent the full range of human sequence variation. Generating T2T genomes remains challenging and costly and requires a combination of multiple sequencing data types. It is therefore important to compare T2T assembly variant calling to other available methods – including raw-read alignment and other haplotype-resolved assembly-based methods – to determine if and when T2T assembly is necessary.

Here we compare SV calls from raw-read, haplotype-resolved de novo assembly, and T2T de novo assembly approaches using Oxford Nanopore simplex and duplex whole-genome sequencing data in order to determine the most efficient SV discovery strategy.

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