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feat: add vaf calculation for strelka results #109

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feat: add vaf calculation for strelka results #109

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4bc016d
feat: first steps to add vaf calculation for strelka
famosab Jan 9, 2025
e78b133
fix: snakefmt
famosab Jan 9, 2025
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3 changes: 2 additions & 1 deletion .gitignore
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Original file line number Diff line number Diff line change
Expand Up @@ -6,4 +6,5 @@ resources/**
logs
logs/**
data/**
report/**
report/**
test/**
5 changes: 5 additions & 0 deletions workflow/envs/cyvcf.yaml
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Original file line number Diff line number Diff line change
@@ -0,0 +1,5 @@
channels:
- conda-forge
- bioconda
dependencies:
- cyvcf2
2 changes: 2 additions & 0 deletions workflow/rules/common.smk
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Original file line number Diff line number Diff line change
Expand Up @@ -455,6 +455,8 @@ def get_vaf_status(wildcards):
vaf_benchmark = benchmarks[wildcards.benchmark].get("vaf-field")
if vaf_benchmark is None:
return False
if vaf_benchmark == "tbc":
return True
else:
callsets = get_benchmark_callsets(wildcards.benchmark)
vaf_callsets = [
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13 changes: 13 additions & 0 deletions workflow/rules/eval.smk
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Original file line number Diff line number Diff line change
Expand Up @@ -91,6 +91,19 @@ rule remove_non_pass:
"v3.3.6/bio/bcftools/view"


rule calculate_vaf:
input:
"results/filtered-variants/{callset}.bcf",
output:
"results/calculate-vaf/{callset}.added-vaf.bcf",
log:
"logs/calculate-vaf/",
conda:
"../envs/cyvcf.yaml"
script:
"../scripts/calc-vaf.py"


rule intersect_calls_with_target_regions:
input:
bcf="results/filtered-variants/{callset}.bcf",
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36 changes: 36 additions & 0 deletions workflow/scripts/calc-vaf.py
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@@ -0,0 +1,36 @@
from cyvcf2 import VCF

#vcf = "/Users/famke/01-pm4onco/osf-download/pipeline-results-of-imgag-data/qbic/strelka/tumor_5perc_vs_normal_5perc.strelka.somatic_snvs_VEP.ann.vcf" #snakemake.input
#indel = "/Users/famke/01-pm4onco/osf-download/pipeline-results-of-imgag-data/qbic/strelka/tumor_5perc_vs_normal_5perc.strelka.somatic_indels_VEP.ann.vcf.gz"

#
# SNVS
#

def get_snv_allele_freq(vcf):
for variant in VCF(vcf):
refCounts = variant.format(variant.REF + "U")
altCounts = variant.format(variant.ALT[0] + "U")

# TODO: check which value is the correct one from the matrix (this leads to many zero VAF)
tier1RefCounts = refCounts[0, 0]
tier1AltCounts = altCounts[0, 0]

vaf = tier1AltCounts / (tier1AltCounts + tier1RefCounts)

print(vaf)
Comment on lines +10 to +21
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🛠️ Refactor suggestion

Enhance the SNV VAF calculation implementation.

The current implementation needs improvements:

  1. Add error handling for division by zero
  2. Add docstring explaining the function
  3. Store results instead of just printing
  4. Validate the matrix values as noted in TODO

Here's a suggested implementation:

 def get_snv_allele_freq(vcf):
+    """Calculate Variant Allele Frequency (VAF) for SNVs.
+    
+    Args:
+        vcf: Path to the VCF file containing SNV variants
+        
+    Returns:
+        List of tuples containing (variant_id, vaf)
+    """
+    results = []
     for variant in VCF(vcf):
         refCounts = variant.format(variant.REF + "U")
         altCounts = variant.format(variant.ALT[0] + "U")
 
-        # TODO: check which value is the correct one from the matrix (this leads to many zero VAF)
         tier1RefCounts = refCounts[0, 0]
         tier1AltCounts = altCounts[0, 0]
 
-        vaf = tier1AltCounts / (tier1AltCounts + tier1RefCounts)
+        total_counts = tier1AltCounts + tier1RefCounts
+        if total_counts == 0:
+            vaf = 0.0
+        else:
+            vaf = tier1AltCounts / total_counts
 
-        print(vaf)
+        results.append((variant.ID or f"{variant.CHROM}:{variant.POS}", vaf))
+    return results
📝 Committable suggestion

‼️ IMPORTANT
Carefully review the code before committing. Ensure that it accurately replaces the highlighted code, contains no missing lines, and has no issues with indentation. Thoroughly test & benchmark the code to ensure it meets the requirements.

Suggested change
def get_snv_allele_freq(vcf):
for variant in VCF(vcf):
refCounts = variant.format(variant.REF + "U")
altCounts = variant.format(variant.ALT[0] + "U")
# TODO: check which value is the correct one from the matrix (this leads to many zero VAF)
tier1RefCounts = refCounts[0, 0]
tier1AltCounts = altCounts[0, 0]
vaf = tier1AltCounts / (tier1AltCounts + tier1RefCounts)
print(vaf)
def get_snv_allele_freq(vcf):
"""Calculate Variant Allele Frequency (VAF) for SNVs.
Args:
vcf: Path to the VCF file containing SNV variants
Returns:
List of tuples containing (variant_id, vaf)
"""
results = []
for variant in VCF(vcf):
refCounts = variant.format(variant.REF + "U")
altCounts = variant.format(variant.ALT[0] + "U")
tier1RefCounts = refCounts[0, 0]
tier1AltCounts = altCounts[0, 0]
total_counts = tier1AltCounts + tier1RefCounts
if total_counts == 0:
vaf = 0.0
else:
vaf = tier1AltCounts / total_counts
results.append((variant.ID or f"{variant.CHROM}:{variant.POS}", vaf))
return results




#
# INDELs
#

def get_indel_allele_freq(vcf):
for variant in VCF(vcf):
tier1RefCounts = variant.format("TAR")[0,0]
tier1AltCounts = variant.format("TIR")[0,0]

vaf = tier1AltCounts / (tier1AltCounts + tier1RefCounts)

print(vaf)
Comment on lines +29 to +36
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🛠️ Refactor suggestion

Apply similar improvements to INDEL VAF calculation.

The INDEL function needs the same enhancements as the SNV function.

Here's a suggested implementation:

 def get_indel_allele_freq(vcf):
+    """Calculate Variant Allele Frequency (VAF) for INDELs.
+    
+    Args:
+        vcf: Path to the VCF file containing INDEL variants
+        
+    Returns:
+        List of tuples containing (variant_id, vaf)
+    """
+    results = []
     for variant in VCF(vcf):
         tier1RefCounts = variant.format("TAR")[0,0]
         tier1AltCounts = variant.format("TIR")[0,0]
 
-        vaf = tier1AltCounts / (tier1AltCounts + tier1RefCounts)
+        total_counts = tier1AltCounts + tier1RefCounts
+        if total_counts == 0:
+            vaf = 0.0
+        else:
+            vaf = tier1AltCounts / total_counts
 
-        print(vaf)
+        results.append((variant.ID or f"{variant.CHROM}:{variant.POS}", vaf))
+    return results
📝 Committable suggestion

‼️ IMPORTANT
Carefully review the code before committing. Ensure that it accurately replaces the highlighted code, contains no missing lines, and has no issues with indentation. Thoroughly test & benchmark the code to ensure it meets the requirements.

Suggested change
def get_indel_allele_freq(vcf):
for variant in VCF(vcf):
tier1RefCounts = variant.format("TAR")[0,0]
tier1AltCounts = variant.format("TIR")[0,0]
vaf = tier1AltCounts / (tier1AltCounts + tier1RefCounts)
print(vaf)
def get_indel_allele_freq(vcf):
"""Calculate Variant Allele Frequency (VAF) for INDELs.
Args:
vcf: Path to the VCF file containing INDEL variants
Returns:
List of tuples containing (variant_id, vaf)
"""
results = []
for variant in VCF(vcf):
tier1RefCounts = variant.format("TAR")[0,0]
tier1AltCounts = variant.format("TIR")[0,0]
total_counts = tier1AltCounts + tier1RefCounts
if total_counts == 0:
vaf = 0.0
else:
vaf = tier1AltCounts / total_counts
results.append((variant.ID or f"{variant.CHROM}:{variant.POS}", vaf))
return results

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