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https://github.com/tobiasrausch/breaktracer

Tracing inserted sequence fragments at structural variant breakpoints
https://github.com/tobiasrausch/breaktracer

flt3 insertion mobile-element-insertion mobile-elements tandem-duplication viral-genomics

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Tracing inserted sequence fragments at structural variant breakpoints

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README

          

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# BreakTracer: Tracing inserted sequence fragments at structural variant breakpoints using long-reads

BreakTracer is designed to identify inserted sequence fragments at structural variant (SV) breakpoints using long-read sequencing data. It can detect mobile element insertions, viral sequence integrations, and internal tandem duplications (ITDs), such as FLT3-ITDs. In contrast to generic SV callers like [delly](https://github.com/dellytools/delly), BreakTracer can resolve complex SVs mediated by such insertions and link the inserted sequences to adjacent genomic rearrangements.

## Installing BreakTracer

BreakTracer is available as a [Bioconda package](https://anaconda.org/bioconda/breaktracer), as a pre-compiled [statically linked binary](https://github.com/tobiasrausch/breaktracer/releases/), as a minimal [docker container](https://hub.docker.com/r/trausch/breaktracer/) or as a [singularity containter (SIF file)](https://github.com/tobiasrausch/breaktracer/releases/). The static binaries you can simply download [here](https://github.com/tobiasrausch/breaktracer/releases/) and then make them executable, e.g.:

```
chmod a+x ./breaktracer-v0.2.8-linux-amd64
./breaktracer-v0.2.8-linux-amd64
```

## Building from source

BreakTracer can be built from source using a recursive clone and make. BreakTracer depends on [HTSlib](https://github.com/samtools/htslib) and [Boost](https://www.boost.org/).

`git clone --recursive https://github.com/tobiasrausch/breaktracer.git`

`cd breaktracer/`

`make all`

## Running BreakTracer

BreakTracer has been designed to identify inserted sequence fragments at structural variant (SV) breakpoints using long-read sequencing data. For instance, to identify L1 fragments at SV breakpoints:

`breaktracer find -n L1 -g hg38.fa input.bam > bp.ins.vcf`

BreakTracer can also be used to identify a custom FASTA sequence inserted at SV breakpoints. For instance, to identify a human papillomavirus integration you can use

`breaktracer find -e hpv.seq.fa -g hg38.fa input.bam > bp.ins.vcf`

or with BCF output:

`breaktracer find -e hpv.seq.fa -g hg38.fa -o bp.ins.bcf input.bam`

## Other use cases

As BreakTracer also identifies plain insertions, the method can be used to detect events such as tandem duplications, for example, FLT3 internal tandem duplications (FLT3-ITDs). In this case, the duplicated FLT3 segment serves as the insertion source sequence, which can then be analyzed with BreakTracer.

```
samtools faidx hg38.fa chr13:28033983-28034368 | sed 's/>.*$/>source/' > tdsource.fa
samtools faidx tdsource.fa
```

Make sure to adjust the insertion parameters to detect small insertions (≥15bp). To speed up the analysis, you may also want to subset the BAM file to the region of interest.

```
samtools view -b input.bam chr13:28033983-28034368 > sub.bam
samtools index sub.bam
breaktracer find -m 15 -c 15 -s 15 -r 0 -e tdsource.fa -g hg38.fa sub.bam
```

## License

BreakTracer is free and open source (BSD). Consult the accompanying [LICENSE](https://github.com/tobiasrausch/breaktracer/blob/master/LICENSE) file for more details.

## Credits

[HTSlib](https://github.com/samtools/htslib) is heavily used for alignment processing. [Boost](https://www.boost.org/) for various data structures and algorithms and [Edlib](https://github.com/Martinsos/edlib) for pairwise alignments using edit distance.