VCFX_distance_calculator¶

Overview¶

VCFX_distance_calculator analyzes a VCF file and calculates the distance (in base pairs) between consecutive variants along each chromosome, providing insights into variant density and spacing across the genome.

Usage¶

VCFX_distance_calculator [OPTIONS] < input.vcf > variant_distances.tsv

Options¶

Option	Description
`-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_distance_calculator processes a VCF file to measure the distance between variants on the same chromosome. The tool:

Reads a VCF file line-by-line
Extracts chromosome (CHROM) and position (POS) information from each valid variant
For each chromosome, tracks the position of the previous variant
Calculates the distance from the previous variant to the current one
Outputs a tab-delimited file with the results
Provides summary statistics to stderr, including minimum, maximum, and average distances per chromosome

This tool is useful for: - Analyzing variant density across the genome - Identifying regions with unusually sparse or dense variant coverage - Quality control to detect potential issues with variant calling - Understanding the distribution of variants in targeted sequencing

Output Format¶

The output is a tab-delimited text file with the following columns:

CHROM  POS  PREV_POS  DISTANCE

Where: - CHROM: The chromosome name - POS: The position of the current variant - PREV_POS: The position of the previous variant on the same chromosome (or "NA" for the first variant) - DISTANCE: The distance in base pairs between current and previous positions (or "NA" for the first variant)

Examples¶

Basic Usage¶

./VCFX_distance_calculator < input.vcf > variant_distances.tsv

Analyzing Specific Chromosomes¶

# Extract only chromosome 1 data
grep -P "^chr1\t|^CHROM" variant_distances.tsv > chr1_distances.tsv

Identifying Large Gaps¶

# Find regions with large gaps (>100,000 bp)
./VCFX_distance_calculator < input.vcf | awk -F'\t' '$4 > 100000 {print}' > large_gaps.tsv

Visualizing Distance Distribution¶

# Process output for visualization (e.g., with R or Python)
./VCFX_distance_calculator < input.vcf | \
  grep -v "NA" | cut -f1,4 > distances_for_plotting.tsv

Summary Statistics¶

In addition to the main output file, VCFX_distance_calculator prints summary statistics to stderr:

=== Summary Statistics ===
Chromosome: chr1
  Variants compared: 501
  Distances computed: 500
  Total distance: 10000000
  Min distance: 1
  Max distance: 150000
  Average distance: 20000

This provides a quick overview of variant distribution patterns for each chromosome.

Handling Special Cases¶

First variant on a chromosome: Marked with "NA" for PREV_POS and DISTANCE
Unsorted VCF files: Processes variants in the order they appear, which may result in negative distances
Duplicate positions: Correctly calculates a distance of 0 between variants at the same position
Malformed lines: Warns about and skips lines that don't follow VCF format
Missing header: Requires a proper VCF header (#CHROM line) before processing variant records
Invalid chromosome names: Skips variants with obviously invalid chromosome names
Non-numeric positions: Skips variants where the position cannot be parsed as an integer

Performance¶

The tool is optimized for efficiency: - Processes VCF files line-by-line with minimal memory overhead - Uses hash maps for O(1) lookups of previous positions - Can handle very large VCF files (tested with millions of variants) - Memory usage scales with the number of distinct chromosomes, not with file size

Limitations¶

Does not account for chromosome lengths (cannot detect missing regions)
Does not distinguish between different types of variants
Assumes variants are properly formatted according to VCF specifications
No built-in filtering for quality or other variant attributes
Distances are calculated based on the reference genome coordinates, not actual sequence lengths
Does not handle structural variants in any special way (uses only the position field)