Challenges in structural variant calling in low-complexity regions

2025/09/27 by Qian Qin, Heng Li, Qin, Qian +1 · 2 voices · 1 citation
#q-bio.GN

paper · pdf · doi:10.48550/arxiv.2509.23057

Abstract

Background: Structural variants (SVs) are genomic differences ≥50 bp in length. They remain challenging to detect even with long sequence reads, and the sources of these difficulties are not well quantified. Results: We identified 35.4 Mb of low-complexity regions (LCRs) in GRCh38. Although these regions cover only 1.2% of the genome, they contain 69.1% of confident SVs in sample HG002. Across long-read SV callers, 77.3-91.3% of erroneous SV calls occur within LCRs, with error rates increasing with LCR length. Conclusion: SVs are enriched and difficult to call in LCRs. Special care need to be taken for calling and analyzing these variants.

Citations

• Finding low-complexity DNA sequences with longdust
• Sawfish: improving long-read structural variant discovery and genotyping with local haplotype modeling

Cited by

• Finding low-complexity DNA sequences with longdust
• Efficient near-telomere-to-telomere assembly of nanopore simplex reads

Discussions

• Do you know ~60% of human SVs fall in ~1% of GRCh38? See our new preprint: arxiv.org/abs/2509.23057 and the companion blog post on how we started this project and longdust: lh3.github.io/2025/09/29/o. [bsky, 83 points, 0 comments]
• Qian Qin, Heng Li: Challenges in structural variant calling in low-complexity regions https://arxiv.org/abs/2509.23057 https://arxiv.org/pdf/2509.23057 https://arxiv.org/html/2509.23057 [bsky, 0 points, 0 comments]

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