Indel detection from DNA and RNA sequencing data with transIndel

Abstract

BackgroundInsertions 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.ResultsHere, 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-the-art 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.ConclusionsOur 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.Electronic supplementary materialThe online version of this article (10.1186/s12864-018-4671-4) contains supplementary material, which is available to authorized users.

Comparative Transcriptome Profiling of Skeletal Muscle from Black Muscovy Duck at Different Growth Stages Using RNA-seq

“…These candidate genes could be used as molecular markers in early marker-assisted selection in animal breeding programs [ 22 , 23 ]. InDels are a major class of genomic variation, which are primarily detected from DNA-seq data [ 24 , 25 ]. In order to explore the gene SNPs and InDels related to muscle growth and development, gene levels of the breast and leg muscle tissues were analyzed by high throughput RNA sequencing technology.…”

Neoantigen prediction in human breast cancer using RNA sequencing data

“…It has been reported that STAR aligner misidentified indels as soft clips at read lengths ≤50 bp, but the detection rate of indels improved at read lengths of 100 bp 54 . As several software programs have been developed for indel‐sensitive detection with RNA‐seq data, 55,56 the detection rate of indels could be improved using longer read length and appropriate tools. Moreover, longer read length is known to improve the detection of the splice junction 57 .…”

ScanITD: Detecting internal tandem duplication with robust variant allele frequency estimation

“…(a) If ITD size is less than the read length, ScanITD reconstructs ITDs as insertions based on the transIndel algorithm [ 10 ], which will modify the CIGAR string and update the start position of the chimeric read (Fig. 1B ).…”