期刊
BMC GENOMICS
卷 19, 期 -, 页码 -出版社
BIOMED CENTRAL LTD
DOI: 10.1186/s12864-018-4671-4
关键词
Indel detection; RNA-seq; DNA-seq; TCGA; Cancer genome; Exitron; Metastasis
资金
- National Cancer Institute grant [R01CA17777]
- Young Investigator Award from the Prostate Cancer Foundation
- NATIONAL CANCER INSTITUTE [R01CA174777, T32CA009138] Funding Source: NIH RePORTER
Background: Insertions and deletions (indels) are a major class of genomic variation associated with human disease. Indels are primarily detected from DNA sequencing (DNA-seq) data but their transcriptional consequences remain unexplored due to challenges in discriminating medium-sized and large indels from splicing events in RNA-seq data. Results: Here, we developed transIndel, a splice-aware algorithm that parses the chimeric alignments predicted by a short read aligner and reconstructs the mid-sized insertions and large deletions based on the linear alignments of split reads from DNA-seq or RNA-seq data. TransIndel exhibits competitive or superior performance over eight state-of-theart indel detection tools on benchmarks using both synthetic and real DNA-seq data. Additionally, we applied transIndel to DNA-seq and RNA-seq datasets from 333 primary prostate cancer patients from The Cancer Genome Atlas (TCGA) and 59 metastatic prostate cancer patients from AACR-PCF Stand-Up-To-Cancer (SU2C) studies. TransIndel enhanced the taxonomy of DNA-and RNA-level alterations in prostate cancer by identifying recurrent FOXA1 indels as well as exitron splicing in genes implicated in disease progression. Conclusions: Our study demonstrates that transIndel is a robust tool for elucidation of medium-and large-sized indels from DNA-seq and RNA-seq data. Including RNA-seq in indel discovery efforts leads to significant improvements in sensitivity for identification of med-sized and large indels missed by DNA-seq, and reveals non-canonical RNA-splicing events in genes associated with disease pathology.
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