Agent skill

structural-variant-calling

View SKILL.md on GitHub Repository
Stars 2,009
Forks 275

Install this agent skill to your Project

npx add-skill https://github.com/FreedomIntelligence/OpenClaw-Medical-Skills/tree/main/skills/variant-interpretation-acmg/bioSkills/structural-variant-calling

SKILL.md

name: bio-variant-calling-structural-variant-calling description: Call structural variants (SVs) from short-read sequencing using Manta, Delly, and LUMPY. Detects deletions, insertions, inversions, duplications, and translocations that are too large for standard SNV callers. Use when detecting structural variants from short-read data. tool_type: cli primary_tool: manta measurable_outcome: Execute skill workflow successfully with valid output within 15 minutes. allowed-tools:

  • read_file
  • run_shell_command

Structural Variant Calling (Short Reads)

Manta (Recommended)

bash
# Configure Manta run (creates runWorkflow.py)
configManta.py \
    --bam sample.bam \
    --referenceFasta reference.fa \
    --runDir manta_run

# Execute
manta_run/runWorkflow.py -j 8

# Output: manta_run/results/variants/
# - diploidSV.vcf.gz (germline SVs)
# - candidateSV.vcf.gz (all candidates)
# - candidateSmallIndels.vcf.gz (small indels)

Manta Tumor-Normal Mode

bash
# Somatic SV calling
configManta.py \
    --tumorBam tumor.bam \
    --normalBam normal.bam \
    --referenceFasta reference.fa \
    --runDir manta_somatic

manta_somatic/runWorkflow.py -j 8

# Output includes:
# - somaticSV.vcf.gz (somatic SVs)
# - diploidSV.vcf.gz (germline SVs)

Manta Options

bash
# WES mode (for exome data)
configManta.py \
    --bam sample.bam \
    --referenceFasta reference.fa \
    --exome \                          # Use exome settings
    --callRegions regions.bed.gz \     # Restrict to regions
    --runDir manta_exome

# RNA-seq mode
configManta.py \
    --bam rnaseq.bam \
    --referenceFasta reference.fa \
    --rna \                            # RNA-seq mode
    --runDir manta_rna

Delly

bash
# Call SVs
delly call \
    -g reference.fa \
    -o sv_calls.bcf \
    sample.bam

# Convert to VCF
bcftools view sv_calls.bcf > sv_calls.vcf

# Multiple samples (joint calling)
delly call \
    -g reference.fa \
    -o joint_svs.bcf \
    sample1.bam sample2.bam sample3.bam

Delly Somatic Mode

bash
# Call with tumor-normal
delly call \
    -g reference.fa \
    -o svs.bcf \
    tumor.bam normal.bam

# Create sample file
echo -e "tumor\ttumor\nnormal\tcontrol" > samples.tsv

# Filter for somatic
delly filter \
    -f somatic \
    -o somatic_svs.bcf \
    -s samples.tsv \
    svs.bcf

Delly SV Types

bash
# Call specific SV type
delly call -t DEL -g ref.fa -o deletions.bcf sample.bam
delly call -t DUP -g ref.fa -o duplications.bcf sample.bam
delly call -t INV -g ref.fa -o inversions.bcf sample.bam
delly call -t BND -g ref.fa -o translocations.bcf sample.bam
delly call -t INS -g ref.fa -o insertions.bcf sample.bam

LUMPY

bash
# Extract split reads and discordant pairs
samtools view -b -F 1294 sample.bam > discordant.bam
samtools view -h sample.bam | \
    /path/to/lumpy-sv/scripts/extractSplitReads_BwaMem -i stdin | \
    samtools view -Sb - > splitters.bam

# Run LUMPY
lumpyexpress \
    -B sample.bam \
    -S splitters.bam \
    -D discordant.bam \
    -o lumpy_svs.vcf

Smoove (LUMPY Wrapper)

bash
# Simplified LUMPY workflow
smoove call \
    --name sample \
    --fasta reference.fa \
    --outdir smoove_output \
    -p 8 \
    sample.bam

# Output: smoove_output/sample-smoove.genotyped.vcf.gz

Merge Multiple Callers

bash
# Use SURVIVOR to merge callsets
# Create file listing VCFs
ls manta_svs.vcf delly_svs.vcf lumpy_svs.vcf > vcf_list.txt

# Merge with parameters
SURVIVOR merge vcf_list.txt 1000 2 1 1 0 50 merged_svs.vcf

# Parameters: max_dist min_callers type_agree strand_agree estimate_dist min_size

Filter SV Calls

bash
# Filter by quality
bcftools view -i 'QUAL >= 20' svs.vcf > svs.filtered.vcf

# Filter by size
bcftools view -i 'ABS(SVLEN) >= 50' svs.vcf > svs.min50.vcf

# Filter by SV type
bcftools view -i 'SVTYPE="DEL"' svs.vcf > deletions.vcf
bcftools view -i 'SVTYPE="INS"' svs.vcf > insertions.vcf
bcftools view -i 'SVTYPE="INV"' svs.vcf > inversions.vcf
bcftools view -i 'SVTYPE="DUP"' svs.vcf > duplications.vcf
bcftools view -i 'SVTYPE="BND"' svs.vcf > translocations.vcf

# Keep only PASS
bcftools view -f PASS svs.vcf > svs.pass.vcf

Annotate SVs

bash
# AnnotSV annotation
AnnotSV \
    -SVinputFile svs.vcf \
    -genomeBuild GRCh38 \
    -outputFile annotated_svs

# Output includes: genes, DGV, gnomAD-SV, ClinVar

SV Types

Type Code Description
Deletion DEL Sequence removed
Insertion INS Sequence inserted
Inversion INV Sequence reversed
Duplication DUP Sequence duplicated
Translocation BND Breakend (inter-chromosomal)

Comparison: Manta vs Delly vs LUMPY

Feature Manta Delly LUMPY
Speed Fast Medium Medium
Sensitivity High High High
Small SVs Good Moderate Good
Large SVs Good Good Good
RNA-seq Yes No No
Somatic Yes Yes Limited

Coverage Guidelines

Coverage Detection Ability
10x Large SVs (>1kb)
30x Most SVs
50x+ Small SVs, better breakpoints

Long-Read SV Callers

For long-read data (ONT/PacBio HiFi), use specialized callers with higher sensitivity:

Caller Best For Notes
CuteSV ONT/HiFi Fast, accurate for all SV types
Sniffles2 ONT/HiFi Population-scale, multisample
PBSV PacBio Official PacBio caller

See long-read-sequencing/structural-variants for long-read SV workflows.

Related Skills

  • long-read-sequencing/structural-variants - Long-read SV calling
  • copy-number/cnvkit-analysis - Copy number variants
  • variant-calling/filtering-best-practices - Filter VCF files
  • alignment-files/alignment-filtering - Prepare BAM files

Recommended Agent Skills

Expand your agent's capabilities with these related and highly-rated skills.

FreedomIntelligence/OpenClaw-Medical-Skills

vcf-annotator

Annotate VCF variants with VEP, ClinVar, gnomAD frequencies, and ancestry-aware context. Generates prioritised variant reports.

2,009 275
Explore
FreedomIntelligence/OpenClaw-Medical-Skills

chemist-analyst

Analyzes events through chemistry lens using molecular structure, reaction mechanisms, thermodynamics, kinetics, and analytical techniques (spectroscopy, chromatography, mass spectrometry). Provides insights on chemical processes, material properties, reaction pathways, synthesis, and analytical methods. Use when: Chemical reactions, material analysis, synthesis planning, process optimization, environmental chemistry. Evaluates: Molecular structure, reaction mechanisms, yield, selectivity, safety, environmental impact.

2,009 275
Explore
FreedomIntelligence/OpenClaw-Medical-Skills

bio-alignment-io

Read, write, and convert multiple sequence alignment files using Biopython Bio.AlignIO. Supports Clustal, PHYLIP, Stockholm, FASTA, Nexus, and other alignment formats for phylogenetics and conservation analysis. Use when reading, writing, or converting alignment file formats.

2,009 275
Explore
FreedomIntelligence/OpenClaw-Medical-Skills

sleep-analyzer

分析睡眠数据、识别睡眠模式、评估睡眠质量，并提供个性化睡眠改善建议。支持与其他健康数据的关联分析。

2,009 275
Explore
FreedomIntelligence/OpenClaw-Medical-Skills

metabolomics-workbench-database

Access NIH Metabolomics Workbench via REST API (4,200+ studies). Query metabolites, RefMet nomenclature, MS/NMR data, m/z searches, study metadata, for metabolomics and biomarker discovery.

2,009 275
Explore
FreedomIntelligence/OpenClaw-Medical-Skills

bio-hi-c-analysis-matrix-operations

Balance, normalize, and transform Hi-C contact matrices using cooler and cooltools. Apply iterative correction (ICE), compute expected values, and generate observed/expected matrices. Use when normalizing or transforming Hi-C matrices.

2,009 275
Explore

Didn't find tool you were looking for?

Be as detailed as possible for better results