VCFX Tools Overview

VCFX is a collection of C/C++ tools for processing and analyzing VCF (Variant Call Format) files, with optional WebAssembly compatibility. Each tool is an independent command-line executable that can parse input from stdin and write to stdout, enabling flexible piping and integration into bioinformatics pipelines.

The suite also includes a convenience wrapper vcfx so you can run commands as vcfx <subcommand>. For example, vcfx variant_counter is equivalent to running VCFX_variant_counter. Use vcfx --list or the alias vcfx list to see available subcommands. To view Markdown documentation for a tool, run vcfx help <tool>. All individual VCFX_* binaries remain available if you prefer calling them directly. Every tool now supports the common flags --help and --version for quick usage or version information.

Tool Categories

Data Analysis

These tools help extract statistical information and insights from variant data:

• VCFX_allele_freq_calc - Calculate allele frequencies
• VCFX_variant_classifier - Classify variants into SNP, INDEL, MNV, or STRUCTURAL
• VCFX_inbreeding_calculator - Calculate inbreeding coefficients
• VCFX_dosage_calculator - Calculate allele dosage from genotypes
• VCFX_hwe_tester - Test for Hardy-Weinberg equilibrium
• VCFX_distance_calculator - Calculate genetic distances between samples
• VCFX_allele_counter - Count alleles in VCF files
• VCFX_allele_balance_calc - Calculate allele balance metrics
• VCFX_variant_counter - Count variants in VCF files
• VCFX_ancestry_inferrer - Infer ancestry from genetic data
• VCFX_ancestry_assigner - Assign ancestry to samples
• VCFX_ld_calculator - Calculate pairwise linkage disequilibrium (r²) between variants

Data Filtering

Tools for selecting variants based on specific criteria:

• VCFX_phase_checker - Filter variants to keep only fully phased genotypes
• VCFX_phred_filter - Filter variants based on Phred-scaled quality scores
• VCFX_record_filter - Filter variants based on various VCF fields
• VCFX_gl_filter - Filter variants based on genotype likelihoods
• VCFX_allele_balance_filter - Filter variants based on allele balance
• VCFX_population_filter - Filter variants based on population statistics
• VCFX_probability_filter - Filter variants based on probability scores
• VCFX_nonref_filter - Filter to keep only non-reference variants
• VCFX_impact_filter - Filter variants based on predicted impact
• VCFX_phase_quality_filter - Filter variants based on phasing quality scores
• VCFX_region_subsampler - Filter variants based on genomic regions

Data Transformation

Tools for converting or reformatting VCF data:

• VCFX_multiallelic_splitter - Split multiallelic variants into biallelic records
• VCFX_sample_extractor - Extract specific samples from a VCF file
• VCFX_position_subsetter - Extract variants at specific positions
• VCFX_format_converter - Convert VCF files to other formats
• VCFX_genotype_query - Query specific genotype patterns
• VCFX_indel_normalizer - Normalize indel representations
• VCFX_sv_handler - Handle structural variants in VCF files
• VCFX_fasta_converter - Convert VCF files to FASTA format
• VCFX_sorter - Sort VCF files by position
• VCFX_af_subsetter - Extract variants based on allele frequency
• VCFX_reformatter - Reformat VCF files for better readability

Quality Control

Tools for validating and checking data quality:

• VCFX_concordance_checker - Check concordance between samples in a VCF file
• VCFX_missing_detector - Detect and report missing data
• VCFX_outlier_detector - Detect outlier samples or variants
• VCFX_alignment_checker - Check alignment of variants
• VCFX_cross_sample_concordance - Check concordance between samples
• VCFX_validator - Validate VCF format compliance

File Management

Tools for handling VCF files:

• VCFX_indexer - Create an index file for random access
• VCFX_file_splitter - Split VCF files into smaller chunks
• VCFX_compressor - Compress VCF files efficiently
• VCFX_diff_tool - Find differences between VCF files
• VCFX_subsampler - Subsample variants from a VCF file
• VCFX_duplicate_remover - Remove duplicate variants
• VCFX_merger - Merge multiple VCF files by position

Annotation and Reporting

Tools for annotating and extracting information from VCF files:

• VCFX_custom_annotator - Add custom annotations to VCF files
• VCFX_info_summarizer - Summarize INFO fields in VCF files
• VCFX_header_parser - Parse and extract information from VCF headers
• VCFX_annotation_extractor - Extract annotations from VCF files
• VCFX_ref_comparator - Compare variants against a reference genome
• VCFX_field_extractor - Extract specific fields from VCF files
• VCFX_info_aggregator - Aggregate INFO fields across variants
• VCFX_info_parser - Parse INFO fields in VCF files
• VCFX_metadata_summarizer - Summarize key metadata from VCF files

Data Processing

Tools for processing variants and samples:

• VCFX_missing_data_handler - Handle missing data in VCF files
• VCFX_quality_adjuster - Adjust quality scores in VCF files
• VCFX_haplotype_phaser - Phase haplotypes in VCF files
• VCFX_haplotype_extractor - Extract haplotype information

Common Usage Patterns

VCFX tools are designed to be combined in pipelines. Here are some common usage patterns:

Basic Filtering and Analysis

# Extract phased variants, filter by quality, and calculate allele frequencies
cat input.vcf | \
  VCFX_phase_checker | \
  VCFX_phred_filter --phred-filter 30 | \
  VCFX_allele_freq_calc > result.tsv

Variant Classification and Filtering

# Classify variants and filter for SNPs with high quality
cat input.vcf | \
  VCFX_variant_classifier --append-info | \
  grep 'VCF_CLASS=SNP' | \
  VCFX_phred_filter --phred-filter 30 > high_quality_snps.vcf

Sample Comparison

# Check concordance between two samples in a single VCF
cat input.vcf | VCFX_concordance_checker --samples "SAMPLE1 SAMPLE2" > concordance.tsv

Linkage Disequilibrium Analysis

# Calculate LD in a specific region after filtering for common variants
cat input.vcf | \
  VCFX_af_subsetter --af-filter '0.05-1.0' | \
  VCFX_ld_calculator --region chr1:10000-20000 > ld_matrix.txt

Normalization and Splitting

# Normalize indels and split multiallelic variants
cat input.vcf | \
  VCFX_indel_normalizer | \
  VCFX_multiallelic_splitter > normalized_biallelic.vcf

Population Analysis

# Extract population-specific VCFs and calculate allele frequencies
cat input.vcf | VCFX_population_filter --population EUR --pop-map pop_map.txt > eur.vcf
cat eur.vcf | VCFX_allele_freq_calc > eur_afs.tsv

Quality Control Pipeline

# Validate, classify, detect missing data, and filter by quality
cat input.vcf | \
  VCFX_validator | \
  VCFX_variant_classifier --append-info | \
  VCFX_missing_detector --max-missing 0.1 | \
  VCFX_phred_filter --phred-filter 20 > qc_passed.vcf