Challenges in structural variant calling in low-complexity regions

Abstract

Background Structural variants (SVs) are genomic differences $\ge$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 needs to be taken for calling and analyzing these variants.