VCF Reformatter: What is it?

Did it ever happen that you had VCF files and you wanted to have a look at the data as you would do with a normal table? VCF Reformatter is here for your rescue!

A Rust command-line tool for parsing and reformatting VCF (Variant Call Format) files, with support for VEP (Variant Effect Predictor) and SnpEff annotations. This tool flattens complex VCF files into tab-separated values (TSV) format for easier downstream analysis. Also incredibly useful for quick checks to your data!

VCF Reformatter

🚀 Quick Start

# Download binary from releases (easiest! You download and use it)
wget https://github.com/flalom/vcf-reformatter/releases/latest/download/vcf-reformatter-v0.3.0-linux-x86_64
chmod +x vcf-reformatter-v0.3.0-linux-x86_64

# Transform your VCF file  
./vcf-reformatter-v0.3.0-linux-x86_64 sample.vcf.gz

# Generate MAF output ⚠️ (in beta!)
./vcf-reformatter-v0.3.0-linux-x86_64 sample.vcf.gz --output-format maf

OR Via Bioconda

conda install -c bioconda vcf-reformatter
# or
# mamba install vcf-reformatter -c bioconda

OR install from crates.io:

cargo install vcf-reformatter

OR build from source (you need Rust toolchain):

git clone https://github.com/flalom/vcf-reformatter.git
cd vcf-reformatter
cargo build --release
./target/release/vcf-reformatter sample.vcf.gz

⚠️ Experimental MAF support

MAF output is currently in beta testing (v0.3.0). Known limitations:

• VAF calculation needs refinement for some genotype patterns
• Multi-sample handling requires validation
• Use with caution in production workflows

Memory considerations for MAF:

• Files >100K variants: Monitor memory usage
• Files >1M variants: Ensure adequate RAM (16GB+)

🎯 Why VCF Reformatter?

The Problem: VCF files are notoriously difficult to analyze. Complex nested annotations, semicolon-separated INFO fields, and multi-transcript VEP annotations make downstream analysis a nightmare.

The Solution: VCF Reformatter flattens everything into clean, readable TSV format that works seamlessly with Excel, R, Python, and any analysis tool (⚠️ beware Excel auto-correction!).

Before & After

Before (Raw VCF):

chr1  69511  .  A  G  1294.53  .  DP=65;AF=1;CSQ=G|missense_variant|MODERATE|OR4F5|ENSG00000186092...

After (Reformatted TSV):

CHROM  POS    REF  ALT  QUAL     INFO_DP  INFO_AF  CSQ_Allele  CSQ_Consequence      CSQ_SYMBOL
chr1   69511  A    G    1294.53  65       1        G           missense_variant     OR4F5

✨ Key Features

📦 Installation

Option 1: Download Pre-compiled Binaries (Easiest!)

No Rust installation required - just download and run:

1. Go to Releases

2. Download the binary for your platform:

   • vcf-reformatter-v0.3.0-linux-x86_64 → Linux (most users)
   • vcf-reformatter-v0.3.0-linux-x86_64-static → HPC clusters (works everywhere)
   • vcf-reformatter-v0.3.0-windows-x86_64.exe → Windows
   • vcf-reformatter-v0.3.0-macos-x86_64 → Intel Mac
   • vcf-reformatter-v0.3.0-macos-arm64 → Apple Silicon Mac (M1/M2/M3/M4)

3. Make executable and run:

# Linux/Mac
chmod +x vcf-reformatter-*
./vcf-reformatter-* --help

# Windows
# Just double-click or run from command prompt
# C++ might be required, if not already installed

Option 2: Build from Source

git clone https://github.com/flalom/vcf-reformatter.git
cd vcf-reformatter
cargo build --release

Option 3: Docker

# Build the container
docker build -t vcf-reformatter .

# Run with your data
docker run --rm -v $(pwd):/data vcf-reformatter /data/sample.vcf.gz

Option 4: Singularity

# Build Singularity image
singularity build vcf-reformatter.sif Singularity

# Run on HPC cluster
singularity run --bind $PWD:/data vcf-reformatter.sif /data/sample.vcf.gz -j 16

🛠️ Usage

Basic Usage

# Simple conversion
vcf-reformatter input.vcf.gz

# Most severe consequence only (recommended for analysis)
vcf-reformatter input.vcf.gz -t most-severe

# All transcripts in separate rows (comprehensive)
vcf-reformatter input.vcf.gz -t split

Annotation Type Detection

# Auto-detect annotation type (recommended)
vcf-reformatter input.vcf.gz -a auto

# Force VEP processing
vcf-reformatter vep_annotated.vcf.gz -a vep -t most-severe

# Force SnpEff processing  
vcf-reformatter snpeff_annotated.vcf.gz -a snpeff -t most-severe

Advanced Usage

# High-performance processing with compression
vcf-reformatter large_cohort.vcf.gz \
  --transcript-handling most-severe \
  --threads 0 \
  --compress \
  --output-dir results/ \
  --prefix my_analysis \
  --verbose

# Optimized for HPC environments
vcf-reformatter huge_dataset.vcf.gz -t most-severe -j 32 -o /scratch/results/ -c -v

Complete Options

Usage: vcf-reformatter [OPTIONS] <INPUT_FILE>

Arguments:
  <INPUT_FILE>  Input VCF file (supports .vcf.gz)

Options:
  --output-format <FORMAT>     Output format [default: tsv] 
                               [values: tsv, maf]
  --center <CENTER>            Sequencing center for MAF output  
  --ncbi-build <BUILD>         Genome build 
                               [default: GRCh38]
  --sample-barcode <BARCODE>   Sample identifier for MAF output
  -t, --transcript-handling <MODE>  How to handle multiple transcripts
                                   [default: first]
                                   [values: most-severe, first, split]
  -a, --annotation-type <N>        Which annotations to parse VEP/SnpEff
                                   [default: auto]
                                   [values: snpeff, vep, auto]
  -j, --threads <N>                Thread count (0 = auto-detect) [default: 1]
  -o, --output-dir <DIR>           Output directory [default: current]
  -p, --prefix <PREFIX>            Output file prefix [default: input filename]
  -c, --compress                   Compress output with gzip
  -v, --verbose                    Detailed performance statistics
  -h, --help                       Show help
  -V, --version                    Show version

🧬 Transcript Handling Modes

VCF files with VEP annotations often contain multiple transcript annotations per variant. Choose the strategy that fits your analysis:

🎯 Most Severe (--transcript-handling most-severe)

Best for: Clinical analysis, variant prioritization

vcf-reformatter input.vcf.gz -t most-severe

# for maf output
vcf-reformatter input.vcf.gz -t most-severe --output-format maf

Selects the transcript with the most severe consequence (stop_gained > missense_variant > synonymous, etc.)

⚡ First Only (--transcript-handling first) [Default]

Best for: Quick analysis, performance-critical workflows

vcf-reformatter input.vcf.gz  # Uses first transcript by default

Processes only the first transcript annotation (fastest option)

📊 Split All (--transcript-handling split)

Best for: Comprehensive analysis, transcript-level studies

vcf-reformatter input.vcf.gz -t split

Creates separate rows for each transcript (most detailed output)

📈 Performance

Benchmarks

• Small files (< 1K variants): ~5,000 variants/sec
• Medium files (1K-10K variants): ~15,000 variants/sec
• Large files (10K+ variants): ~30,000 variants/sec

Optimization Tips

# Auto-detect optimal thread count
vcf-reformatter input.vcf.gz -j 0

# For files > 10K variants, use parallel processing
vcf-reformatter input.vcf.gz -t most-severe -j 0 -v

# Combine with compression for large outputs
vcf-reformatter input.vcf.gz -t split -j 0 -c -v

📊 Output Format

File Structure

VCF Reformatter generates two files:

• {prefix}_header.txt - Original VCF header and metadata
• {prefix}_reformatted.tsv - Flattened tabular data

Column Types

1. Standard VCF: CHROM, POS, ID, REF, ALT, QUAL, FILTER
2. INFO Fields: INFO_DP, INFO_AF, INFO_AC, etc.
3. VEP Annotations: CSQ_Allele, CSQ_Consequence, CSQ_SYMBOL, CSQ_Gene, etc.
4. SnpEff Annotations: ANN_Allele, ANN_Annotation_Impact, ANN_Gene_Name, ANN_Distance, etc.
5. Sample Data: SAMPLE1_GT, SAMPLE1_DP, SAMPLE1_AD, etc.

Example Output VEP

CHROM  POS    ID     REF  ALT  QUAL     FILTER  INFO_DP  CSQ_Consequence      CSQ_SYMBOL  SAMPLE1_GT
chr1   69511  .      A    G    1294.53  PASS    65       missense_variant     OR4F5       1/1
chr1   69761  rs123  C    T    892.15   PASS    42       synonymous_variant   OR4F5       0/1

Example Output SnpEff

CHROM  POS    ID     REF  ALT  QUAL     FILTER  INFO_DP  ANN_Annotation          ANN_Gene_Name  SAMPLE1_GT
chr1   69761  rs587   C    T  730  PASS   .     214      synonymous_variant      OR4F5          0/1
chr1   924024  .      A    G  53   PASS   .     409      5_prime_UTR_variant     SAMD11         1/1

🔧 Integration Examples

With R

# Read compressed output directly
library(data.table)
data <- fread("output_reformatted.tsv.gz")

# Quick variant summary
summary(data$CSQ_Consequence)

With Python

import pandas as pd

# Load and analyze
df = pd.read_csv("output_reformatted.tsv.gz", sep="\t", compression="gzip")
df['CSQ_Consequence'].value_counts()

In Workflows

# Nextflow pipeline
vcf-reformatter ${vcf} -t most-severe -j ${task.cpus} -o results/ -c

# Snakemake rule
shell: "vcf-reformatter {input.vcf} -t most-severe -j {threads} -o {params.outdir} -c"

🐳 Container Usage

Docker

# Build once
docker build -t vcf-reformatter .

# Run anywhere
docker run --rm \
  -v $(pwd):/data \
  vcf-reformatter \
  /data/input.vcf.gz \
  -t most-severe -j 4 -o /data/results/ -c

Singularity (HPC)

# On HPC cluster
singularity run \
  --bind $PWD:/data \
  --bind /scratch:/scratch \
  vcf-reformatter.sif \
  /data/large_cohort.vcf.gz \
  -t most-severe -j 16 -o /scratch/results/ -c -v

🧪 Use Cases

🚀 What's New in v0.3.0

• ✅ MAF Output Support (in Beta⚠️) - Direct conversion to Mutation Annotation Format
• ✅ Auto-metadata Detection (in Beta⚠️) - Extracts center/sample info from VCF headers for MAF
• ✅ Memory-Efficient Processing (streaming) - Chunked streaming for large files (>>100K variants)
• ✅ Enhanced Error Handling - Better processing of malformed files
• ✅ Comprehensive Testing - 70+ test cases ensure reliability

Previous Releases

🚀 What's New in v0.2.0

• ✅ SnpEff Support - Full ANN field parsing with intelligent detection
• ✅ Smart Auto-Detection - Automatically identifies VEP vs SnpEff annotations
• ✅ Enhanced Error Handling - Better processing of malformed or headerless files

TODOs

• Add SnpEff support✅
• Output MAF format option✅
• Add stdin to combine with other tools, such as bcftools
• Support for multi-sample VCF files in MAF output

🤝 Contributing

We welcome contributions! Here's how to get started:

1. Fork the repository
2. Create a feature branch: git checkout -b feature-name
3. Add tests for new functionality
4. Commit your changes: git commit -am 'Add feature'
5. Push to the branch: git push origin feature-name
6. Submit a pull request

Development Setup

git clone https://github.com/flalom/vcf-reformatter.git
cd vcf-reformatter
cargo test  # Run the test suite
cargo run -- data/sample.vcf.gz -v  # Test with sample data

📝 License

This project is licensed under the MIT License - see the LICENSE file for details.

🙏 Acknowledgments

• VCF Format Contributors - For the standard that enables genomic data sharing
• VEP Team - For the powerful variant annotation framework
• Rust Community - For the incredible ecosystem that makes this possible
• Bioinformatics Community - For feedback and feature requests

Frequently Asked Questions

Q: Which transcript handling mode should I use?

• Clinical analysis: --transcript-handling most-severe
• Quick exploration: --transcript-handling first
• Comprehensive analysis: --transcript-handling split

Q: How does this compare to other VCF tools?

VCF Reformatter is specifically designed for:

• Converting complex VEP/SnpEff annotations to tabular format
• Handling multiple transcripts intelligently
• High-performance parallel processing
• Easy integration with R/Python workflows

Q: Can I use this in production pipelines?

Yes! VCF Reformatter is designed for production use with:

• Comprehensive error handling
• Docker/Singularity support
• Automated testing
• Stable CLI interface

Q: What's the difference between TSV and MAF output?

• TSV: Direct flattening of VCF fields (default)
• MAF (beta): Standardized cancer genomics format for downstream tools

Q: What if I get out-of-memory errors?

• Use TSV format instead of MAF: vcf-reformatter file.vcf.gz -j 0 -c
• Enable verbose mode to monitor: vcf-reformatter file.vcf.gz -v

📞 Support

• 📋 Issues: GitHub Issues
• 📧 Email: fl@flaviolombardo.site