sv-callers

Structural variants (SVs) are an important class of genetic variation implicated in a wide array of genetic diseases. sv-callers is a Snakemake-based workflow that combines several state-of-the-art tools for detecting SVs in whole genome sequencing (WGS) data. The workflow is easy to use and deploy on any Linux-based machine. In particular, the workflow supports automated software deployment, easy configuration and addition of new analysis tools as well as enables to scale from a single computer to different HPC clusters with minimal effort.

Dependencies

• Python
• Conda - package/environment management system
• Snakemake - workflow management system
• Xenon CLI - command-line interface to compute and storage resources
• jq - command-line JSON processor (optional)
• YAtiML - library for YAML type inference and schema validation

The workflow includes the following bioinformatics tools:

• SV callers

  • Manta
  • DELLY
  • LUMPY
  • GRIDSS

• Post-processing

  • BCFtools
  • Viola-SV
  • SURVIVOR

The software dependencies can be found in the conda environment files: [1],[2],[3].

1. Clone this repo.

bash git clone https://github.com/GooglingTheCancerGenome/sv-callers.git cd sv-callers

2. Install dependencies.

```bash

download Miniconda3 installer

wget https://repo.continuum.io/miniconda/Miniconda3-latest-Linux-x86_64.sh -O miniconda.sh

install Conda (respond by 'yes')

bash miniconda.sh

update Conda

conda update -y conda

install Mamba

conda install -n base -c conda-forge -y mamba

create a new environment with dependencies & activate it

mamba env create -n wf -f environment.yaml conda activate wf ```

3. Configure the workflow.

• config files:

  • analysis.yaml - analysis-specific settings (e.g., workflow mode, I/O files, SV callers, post-processing or resources used etc.)
  • samples.csv - list of (paired) samples

• input files:

  • example data in workflow/data directory
  • reference genome in .fasta (incl. index files)
  • excluded regions in .bed (optional)
  • WGS samples in .bam (incl. index files)

• output files:

  • (filtered) SVs per caller and merged calls in .vcf (incl. index files)

4. Execute the workflow.

bash cd workflow

Locally

```bash

'dry' run only checks I/O files

snakemake -np

'vanilla' run if echo_run set to 1 (default) in analysis.yaml,

it merely mimics the execution of SV callers by writing (dummy) VCF files;

SV calling if echo_run set to 0

snakemake --use-conda --jobs

```

Submit jobs to Slurm or GridEngine cluster

bash SCH=slurm # or gridengine snakemake --use-conda --latency-wait 30 --jobs \ --cluster "xenon scheduler $SCH --location local:// submit --name smk.{rule} --inherit-env --cores-per-task {threads} --max-run-time 1 --max-memory {resources.mem_mb} --working-directory . --stderr stderr-%j.log --stdout stdout-%j.log" &>smk.log&

Note: One sample or a tumor/normal pair generates in total 18 SV calling and post-processing jobs. See the workflow instance of single-sample (germline) or paired-sample (somatic) analysis.

To perform SV calling: - edit (default) parameters in analysis.yaml - set echo_run to 0 - choose between two workflow modes: single- (s) or paired-sample (p - default) - select one or more callers using enable_callers (default all)

• use xenon CLI to set:

  • --max-run-time of workflow jobs (in minutes)
  • --temp-space (optional, in MB)

• adjust compute requirements per SV caller according to the system used:

  • the number of threads,
  • the amount of memory(in MB),
  • the amount of temporary disk space or tmpspace (path in TMPDIR env variable) can be used for intermediate files by LUMPY and GRIDSS only.

Query job accounting information

bash SCH=slurm # or gridengine xenon --json scheduler $SCH --location local:// list --identifier [jobID] | jq ...