Picky comprehensively detects high-resolution structural variants in nanopore long reads.
Document Type
Article
Publication Date
6-2018
JAX Source
Nat Methods 2018 Jun; 15:455-460.
ISSN
1548-7105
PMID
29713081
DOI
https://doi.org/10.1038/s41592-018-0002-6
Grant
CA034196
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. Nat Methods 2018 Jun; 15:455-460.
Recommended Citation
Gong L,
Wong C,
Cheng W,
Tjong H,
Menghi F,
Ngan C,
Liu E,
Wei C.
Picky comprehensively detects high-resolution structural variants in nanopore long reads. Nat Methods 2018 Jun; 15:455-460.