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Nat Methods. 2018 Jun;15(6):455-460. doi: 10.1038/s41592-018-0002-6. Epub 2018 Apr 30.

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

Author information

1
The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
2
China Medical University, Taichung, Taiwan.
3
The Jackson Laboratory for Genomic Medicine, Farmington, CT, USA. chia-lin.wei@jax.org.
4
China Medical University, Taichung, Taiwan. chia-lin.wei@jax.org.

Abstract

Acquired genomic structural variants (SVs) are major hallmarks of cancer genomes, but they are challenging to reconstruct from short-read sequencing data. Here we exploited the long reads of the nanopore platform using our customized pipeline, Picky ( https://github.com/TheJacksonLaboratory/Picky ), to reveal SVs of diverse architecture in a breast cancer model. We identified the full spectrum of SVs with superior specificity and sensitivity relative to short-read analyses, and uncovered repetitive DNA as the major source of variation. Examination of genome-wide breakpoints at nucleotide resolution uncovered micro-insertions as the common structural features associated with SVs. Breakpoint density across the genome is associated with the propensity for interchromosomal connectivity and was found to be enriched in promoters and transcribed regions of the genome. Furthermore, we observed an over-representation of reciprocal translocations from chromosomal double-crossovers through phased SVs. We demonstrate that Picky analysis is an effective tool for comprehensive detection of SVs in cancer genomes from long-read data.

PMID:
29713081
PMCID:
PMC5990454
DOI:
10.1038/s41592-018-0002-6
[Indexed for MEDLINE]
Free PMC Article

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