Picky comprehensively detects high-resolution structural variants in nanopore long reads.

Area of Science:

• Genomics
• Cancer Biology
• Bioinformatics

Background:

• Acquired genomic structural variants (SVs) are critical cancer hallmarks.
• Reconstructing complex SVs from short-read sequencing data presents significant challenges.

Purpose of the Study:

• To leverage nanopore long-read sequencing and a custom pipeline (Picky) for comprehensive SV detection in a breast cancer model.
• To characterize the architecture and genomic context of SVs with high resolution.

Main Methods:

• Utilized nanopore long-read sequencing technology.
• Developed and applied a customized bioinformatics pipeline named Picky.
• Analyzed genome-wide breakpoints at nucleotide resolution.

Main Results:

• Identified the full spectrum of SVs with enhanced specificity and sensitivity compared to short-read methods.
• Uncovered repetitive DNA as a primary source of genomic variation.
• Characterized micro-insertions as common structural features at SV breakpoints.
• Found breakpoint density associated with interchromosomal connectivity, enriched in promoters and transcribed regions.
• Observed an enrichment of reciprocal translocations resulting from chromosomal double-crossovers.

Conclusions:

• The Picky pipeline is an effective tool for comprehensive SV detection in cancer genomes using long-read data.
• Long-read sequencing significantly improves the resolution and accuracy of SV analysis in cancer research.