genomics-pipeline

Step 19: Structural Variant Calling with Delly

What This Does

Third structural variant caller — combines paired-end, split-read, and read-depth signals for comprehensive SV detection including deletions, duplications, inversions, translocations, and insertions.

Why

Using multiple SV callers and intersecting their results dramatically reduces false positives:

Manta (step 4): Fast, sensitive for smaller SVs and indels
CNVnator (step 18): Best for large CNVs via read-depth only
Delly: Most balanced — uses all three signal types, especially strong for inversions and translocations

SVs called by 2+ callers have lower false-positive rates than single-caller calls. Multi-caller intersection is a common strategy in WGS pipelines, though dedicated tools like SURVIVOR or Jasmine provide more precise breakpoint-aware merging than simple position overlap.

Tool

Delly (Rausch et al., Bioinformatics 2012)

Docker Image

quay.io/biocontainers/delly:1.7.3--hd6466ae_0

Command

# SV calling (all SV types)
docker run --rm \
  --cpus 4 --memory 8g \
  -v ${GENOME_DIR}:/genome \
  quay.io/biocontainers/delly:1.7.3--hd6466ae_0 \
  delly call \
    -g /genome/reference/Homo_sapiens_assembly38.fasta \
    -o /genome/${SAMPLE}/delly/${SAMPLE}_sv.bcf \
    /genome/${SAMPLE}/aligned/${SAMPLE}_sorted.bam

# Convert BCF to VCF for downstream tools
docker run --rm \
  -v ${GENOME_DIR}:/genome \
  staphb/bcftools:1.21 \
  bcftools view \
    /genome/${SAMPLE}/delly/${SAMPLE}_sv.bcf \
    -Oz -o /genome/${SAMPLE}/delly/${SAMPLE}_sv.vcf.gz

# Index
docker run --rm \
  -v ${GENOME_DIR}:/genome \
  staphb/bcftools:1.21 \
  bcftools index -t \
    /genome/${SAMPLE}/delly/${SAMPLE}_sv.vcf.gz

Optional: Dedicated CNV Calling

Delly also has a dedicated CNV mode using read-depth only (similar to CNVnator):

docker run --rm \
  --cpus 4 --memory 8g \
  -v ${GENOME_DIR}:/genome \
  quay.io/biocontainers/delly:1.7.3--hd6466ae_0 \
  delly cnv \
    -g /genome/reference/Homo_sapiens_assembly38.fasta \
    -o /genome/${SAMPLE}/delly/${SAMPLE}_cnv.bcf \
    /genome/${SAMPLE}/aligned/${SAMPLE}_sorted.bam

Output

${SAMPLE}_sv.bcf / ${SAMPLE}_sv.vcf.gz — SV calls in VCF format
Each SV has type (DEL, DUP, INV, BND, INS), quality, genotype, and supporting read counts

Filtering

# Keep only PASS variants
bcftools view -f PASS ${SAMPLE}_sv.vcf.gz

# Filter by SV type
bcftools view -i 'INFO/SVTYPE="DEL"' ${SAMPLE}_sv.vcf.gz
bcftools view -i 'INFO/SVTYPE="INV"' ${SAMPLE}_sv.vcf.gz

Runtime

~2-4 hours per 30X WGS genome.

Notes

Delly outputs BCF by default (not VCF). Convert with bcftools view for compatibility.
For consensus SV calling, use SURVIVOR or bcftools to merge calls from Manta + Delly + CNVnator.
Delly is the most accurate caller for inversions and balanced translocations.
The delly cnv mode is optional if you already run CNVnator — it provides similar depth-based CNV calls.
Can be run in parallel with Manta and CNVnator (all independent after alignment).

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