VariantCentrifuge: Clinical Variant Analysis Tool for VCF Files

VariantCentrifuge is a powerful Python-based command-line tool for filtering, analyzing, and interpreting genetic variants from VCF (Variant Call Format) files. Designed for clinical geneticists, bioinformaticians, and researchers, it streamlines the identification of disease-causing variants through sophisticated filtering, Mendelian inheritance analysis, and comprehensive reporting.

Why Choose VariantCentrifuge?

VariantCentrifuge addresses the critical challenges in clinical variant interpretation by providing:

🧬 Advanced Variant Filtering

  • Gene-Centric Analysis: Focus on specific genes of interest with automatic region extraction

  • Rare Variant Detection: Identify clinically relevant rare variants using population frequency databases

  • Impact-Based Filtering: Prioritize high and moderate impact variants using SnpEff annotations

  • Custom Filter Presets: 20+ pre-configured filters for common clinical scenarios

🔬 Clinical Interpretation Features

  • Mendelian Inheritance Analysis: Automatically detect de novo, recessive, dominant, and compound heterozygous patterns

  • ACMG Classification Support: Integrate pathogenicity predictions and clinical significance

  • Phenotype Integration: Link variants to patient phenotypes for enhanced interpretation

  • Custom Variant Scoring: Apply configurable scoring algorithms for variant prioritization

📊 Comprehensive Analysis Tools

  • Gene Burden Testing: Statistical analysis for case-control studies using Fisher’s exact test

  • Compound Heterozygous Detection: Optimized algorithm (10-50x faster) for identifying compound het variants

  • Multi-Sample Support: Analyze families, trios, and cohorts with pedigree files

  • Performance Optimization: Handle large VCF files with chunked processing and parallel execution

📈 Professional Reporting

  • Interactive HTML Reports: Sortable tables, filtering, and search functionality

  • IGV.js Integration: Visualize variants directly in the browser with genomic context

  • Excel Export: Generate formatted Excel workbooks for clinical review

  • Detailed Statistics: Comprehensive variant and gene-level statistics

Quick Start

# Basic usage
variantcentrifuge \
  --gene-name BICC1 \
  --vcf-file input.vcf.gz \
  --output-file output.tsv

# With custom filters and Excel output
variantcentrifuge \
  --gene-name BICC1 \
  --vcf-file input.vcf.gz \
  --filters "((dbNSFP_gnomAD_exomes_AC[0] <= 2) & (ANN[ANY].IMPACT has 'HIGH'))" \
  --xlsx

Documentation Contents

User Guide

API Reference

Development

External Dependencies

VariantCentrifuge requires these bioinformatics tools to be installed and available in your PATH:

  • bcftools - VCF manipulation

  • snpEff - Functional annotation and BED file generation

  • SnpSift - Variant filtering and field extraction

  • bedtools - BED file operations

Getting Help

  • Issues: Report bugs and request features on GitHub Issues

  • Discussions: Join the conversation by creating an issue

  • Documentation: Browse the complete documentation on this site

License

This project is licensed under the MIT License.

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