nf-cmgg/exomecnv is a bioinformatics pipeline that can be used to call copy number variations (CNVs) from exome sequencing data with ExomeDepth and annotate these with EnsemblVEP. It takes a samplesheet with mosdepth *per-base.bed.gz, *cram or *bam files and their index files as input, generates read count data in a region of interest bed file, calls CNVs and ends with an annotation. It is also possible to take a samplesheet with VCF files and their index files as input and only execute the annotation step.

1. Input samplesheet check
2. Mosdepth read counting per sample if CRAM/BAM files are provided
3. Extract mean coverage from the mosdepth per-base coverage bed files for the ROI regions with bedtools map
4. Merge count files per batch
5. ExomeDepth CNV calling per sample
6. Convert ExomeDepth output files to VCF with bedgovcf + sort VCF with bcftools
7. Annotate VCF files with EnsemblVEP

First, prepare a samplesheet with your input data that looks as follows:

samplesheet.csv:

sample,batch,family,bed,bed_index,vcf,tbi
Sample1,prep_M,Fam1,/path/to/bed/Sample1.per-base.bed.gz,/path/to/bed_index/Sample1.per-base.bed.gz.csi
Sample2,prep_F,Fam2,/path/to/bed/Sample2.per-base.bed.gz,/path/to/bed_index/Sample2.per-base.bed.gz.csi,/path/to/Sample2.vcf,/path/to/Sample2.vcf.tbi

Each row represents a sample with the associated batch and family, followed by the paths to the BED/BED_INDEX, CRAM/CRAI or VCF/TBI files, depending on which tasks should be executed.

Now, you can run the pipeline using:

nextflow run nf-cmgg/exomecnv \
   -profile <docker/conda> \
   --input /path/to/samplesheet.csv \
   --outdir /path/to/outdir \
   --vep_cache /path/to/vep_cache \
   --exomedepth \
   --annotate

to execute the ExomeDepth workflow, followed by an EnsemblVEP annotation. The --annotate parameter is optional. If not provided, only the ExomeDepth workflow will be executed.

nf-cmgg/exomecnv was originally written by BertGalle and Toros.

We thank the following people for their extensive assistance in the development of this pipeline: nvnieuwk and matthdsm

If you would like to contribute to this pipeline, please see the contributing guidelines.

An extensive list of references for the tools used by the pipeline can be found in the CITATIONS.md file.

This pipeline uses code and infrastructure developed and maintained by the nf-core community, reused here under the MIT license.

The nf-core framework for community-curated bioinformatics pipelines.

Philip Ewels, Alexander Peltzer, Sven Fillinger, Harshil Patel, Johannes Alneberg, Andreas Wilm, Maxime Ulysse Garcia, Paolo Di Tommaso & Sven Nahnsen.

Nat Biotechnol. 2020 Feb 13. doi: 10.1038/s41587-020-0439-x.