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VCFX_concordance_checker

Overview

VCFX_concordance_checker compares genotypes between two specified samples within a VCF file to determine concordance (agreement) or discordance (disagreement) for each variant. This tool is useful for comparing genotype calls between different samples, such as technical replicates or related individuals.

Usage

VCFX_concordance_checker --samples "SAMPLE1 SAMPLE2" < input.vcf > concordance_report.tsv

Options

Option Description
-s, --samples "SAMPLE1 SAMPLE2" Required. Names of the two samples to compare, separated by a space
-h, --help Display help message and exit (handled by vcfx::handle_common_flags)
-v, --version Show program version and exit (handled by vcfx::handle_common_flags)

Description

VCFX_concordance_checker analyzes a VCF file and compares the genotypes of two specified samples for each variant. The tool:

  1. Normalizes genotypes by:
  2. Converting phased genotypes (|) to unphased (/)
  3. Sorting alleles numerically (e.g., 1/0 becomes 0/1)
  4. Validating against available alternate alleles
  5. Compares the normalized genotypes between the two samples
  6. Classifies each variant as:
  7. Concordant: Both samples have identical normalized genotypes
  8. Discordant: Samples have different normalized genotypes
  9. Outputs detailed per-variant results to standard output
  10. Provides a summary of concordance statistics to standard error

This tool is particularly useful for: - Quality control of technical replicates - Comparing genotype calls between related samples - Validating sample identity - Assessing reproducibility of variant calling pipelines

Output Format

The tool produces a tab-separated values (TSV) file with the following columns:

Column Description
CHROM Chromosome of the variant
POS Position of the variant
ID Variant identifier
REF Reference allele
ALT Alternate allele(s)
SAMPLE1_GT Normalized genotype of the first sample
SAMPLE2_GT Normalized genotype of the second sample
Concordance Status: Concordant or Discordant

Additionally, a summary of statistics is printed to standard error, including: - Total number of variants compared - Number of concordant genotypes - Number of discordant genotypes

Examples

Basic Usage

Check concordance between two samples in a VCF file: 

VCFX_concordance_checker --samples "SAMPLE1 SAMPLE2" < input.vcf > concordance_report.tsv

Filtering for Discordant Variants

Identify only variants with discordant genotypes: 

VCFX_concordance_checker --samples "SAMPLE1 SAMPLE2" < input.vcf | grep "Discordant" > discordant_variants.tsv

Calculating Concordance Rate

Count concordant variants and calculate rate: 

VCFX_concordance_checker --samples "SAMPLE1 SAMPLE2" < input.vcf > report.tsv 2> stats.txt
grep -c "Concordant" report.tsv > concordant_count.txt

Integration with Other Tools

Use as part of a larger analysis pipeline: 

cat input.vcf | VCFX_record_filter --filter "QUAL>30" | VCFX_concordance_checker --samples "SAMPLE1 SAMPLE2" > high_quality_concordance.tsv

Genotype Normalization

Process

For each sample's genotype, the tool performs the following normalization steps: 1. Extracts the genotype field (GT) 2. Converts all phase separators (|) to unphased separators (/) 3. Splits the genotype into individual allele indices 4. Validates each allele (skips if missing or invalid) 5. Sorts allele indices in ascending order (e.g., 1/0 → 0/1) 6. Rejoins the allele indices with / separators

Example Normalizations

  • 0|1 → 0/1
  • 1/0 → 0/1
  • 1|2 → 1/2
  • 2/1 → 1/2
  • ./1 → (skipped as invalid)
  • 0/0 → 0/0 (unchanged)

Handling Special Cases

Missing Genotypes

  • Genotypes with missing values (./., .) are excluded from comparison
  • Variants where either sample has missing genotypes are skipped

Multi-allelic Variants

  • Alt alleles are parsed from the ALT column (comma-separated)
  • Genotype allele indices are validated against the number of alt alleles
  • For multi-allelic variants, the tool correctly compares numerically sorted genotypes

Phased Genotypes

  • Phasing information is ignored for concordance calculation
  • Genotypes that differ only in phasing are considered concordant (e.g., 0|1 and 0/1)

Invalid Genotypes

  • Genotypes with non-numeric allele indices are skipped
  • Allele indices that exceed the number of alternate alleles are treated as invalid

Malformed VCF Lines

  • Lines with insufficient columns are skipped
  • Lines encountered before the #CHROM header cause an error
  • VCF files without both specified samples cause an error and program termination

Performance Considerations

  • Processes the VCF file line by line, requiring minimal memory
  • No preprocessing or indexing of the VCF file is required
  • Linear time complexity with respect to file size
  • Provides a quick summary of concordance statistics for rapid quality assessment

Limitations

  • Limited to exactly two samples for comparison
  • Only processes diploid genotypes (e.g., 0/1, not haploid 0 or polyploid genotypes)
  • Ignores all FORMAT fields except for GT (genotype)
  • No consideration of genotype quality or other metrics in concordance assessment
  • Cannot generate detailed statistics on concordance by variant type
  • Does not allow customizing concordance criteria beyond exact genotype match