Changelog

All notable changes to VariantCentrifuge will be documented in this file.

The format is based on Keep a Changelog, and this project adheres to Semantic Versioning.

[Unreleased]

No unreleased changes.

[0.15.0] - 2026-02-22

Added

  • Modular association testing framework with pluggable test architecture:

    • Fisher’s exact test with carrier/allele modes, odds ratio, and 95% CI

    • Logistic burden regression for binary traits with Firth fallback for separation

    • Linear burden regression for quantitative traits (OLS)

    • SKAT and SKAT-O with pure Python backend (numpy/scipy, thread-safe); R backend deprecated

    • COAST allelic series test (BMV/DMV/PTV categories); pure Python backend default

    • ACAT-O per-gene omnibus via Cauchy combination; ACAT-V per-variant score within SKAT

  • Covariate system: TSV/CSV covariate files with auto-detected delimiter and categorical encoding

  • PCA integration: PLINK .eigenvec, AKT output, and generic TSV formats; optional AKT subprocess

  • Variant weights: Beta(MAF), uniform, CADD, REVEL, and combined functional weight schemes

  • Diagnostics: Genomic inflation factor (lambda_GC), QQ data TSV, optional matplotlib QQ plot

  • JSON config: "association" section in config.json with validation and CLI override precedence

  • Single FDR strategy: Benjamini-Hochberg correction on ACAT-O p-values only (not per-test)

  • Association testing guide: Comprehensive user documentation with examples and troubleshooting

[0.14.0] - 2026-02-18

Added

  • Modern HTML report — complete UX overhaul of the individual variant report across 5 phases:

    • JS Stack Modernization: DataTables v2, Chart.js (65KB vs Plotly 3.5MB, 98% reduction), Tippy.js tooltips, all assets vendored for offline single-file reports

    • Summary dashboard: metric cards (total variants, genes, samples, impact breakdown, top genes), impact distribution and inheritance pattern charts

    • Semantic color badges: IMPACT (red/orange/amber/gray), ClinVar (red-to-green severity), inheritance patterns (de novo=red, compound het=purple, AD=blue, AR=green, X-linked=teal)

    • Table redesign: sticky GENE column (FixedColumns), dark header, expandable row detail panels, content density toggle (Compact/Regular/Relaxed with localStorage), intelligent column widths, zebra striping

    • Column-level filtering: noUiSlider range sliders for numeric columns (POS, gnomAD AF, CADD), categorical dropdowns (IMPACT, ClinVar, Inheritance), text search (GENE), removable filter chips, “Include missing values” toggle, reactive chart updates

    • Unified toolbar: all controls in one 28px row — entries/page, filters, missing, search, density, show/hide columns, PDF export

    • Accessibility (WCAG 2.1 AA): skip-link, ARIA roles/labels, keyboard-accessible tooltips, SVG icons with screen-reader text, chart data table fallbacks, 4.5:1 contrast ratios on all badges

    • Print/PDF support: @media print stylesheet hiding interactive controls, PDF export via browser print dialog

    • Report metadata footer with filter criteria, VCF source, reference genome, version, and date

    • Expanded summary.json with inheritance distribution, top genes, and sample count

    • Loading skeleton with shimmer animation during DataTable initialization

  • 107 HTML report-specific tests (structure, behavior, assets, accessibility, print)

  • Unified resource auto-detection across pipeline modes

[0.13.1] - 2026-02-16

Fixed

  • Resource auto-detection across pipeline modes

[0.13.0] - 2026-02-16

Added

  • Performance optimization across 7 phases:

    • Benchmark framework with timing instrumentation

    • Vectorized genotype replacement (Pandas-native operations)

    • DataFrame optimization with sanitized column names for itertuples compatibility

    • Inheritance analysis optimization with vectorized deduction

    • Output stage optimization

    • Pipeline I/O elimination (reduced intermediate file writes)

    • Parallelization and chunking with memory-aware chunk sizing

  • Memory management system with SLURM/PBS/cgroup detection

  • Golden file infrastructure for inheritance validation

  • Performance benchmark test suite

[0.12.0] - 2025-12-01

Added

  • Stage-based pipeline architecture (pipeline_core/) with modular stages, dependency graph, topological sort, and parallel execution via ThreadPoolExecutor/ProcessPoolExecutor

  • Restructured Snakemake workflow matching lab pipeline conventions (Issue #68):

    • Snakemake 8+ with min_version("8.0") and executor plugins

    • Schema-validated config (config/config_vc.yaml) and sample sheet (config/samples.tsv)

    • Profile layering: profiles/default/ (resources) + profiles/{bih,charite,local}/ (executor)

    • Auto-detecting launcher script (scripts/run_snakemake.sh) for BIH, Charite, and local

    • Singularity/Apptainer container support via container: directive with conda fallback

  • Docker image on GHCR (ghcr.io/scholl-lab/variantcentrifuge) with all bioinformatics tools pre-installed:

    • Multi-stage build using micromamba for minimal image size

    • CI/CD pipeline with automated builds, Trivy security scanning, and cosign image signing

    • docker-compose.yml with volume mount patterns for data, snpEff databases, and custom scoring configs

    • Non-root container for security best practices

  • Field profiles for annotation database version compatibility (--field-profile):

    • Built-in dbnsfp4 and dbnsfp5 profiles for seamless gnomAD field switching

    • Template syntax {{fragment:param}} for parameterized filter presets

    • --list-field-profiles to show available profiles

    • Custom profiles configurable in config.json without code changes

  • Inheritance analysis with three-pass pipeline (deduction, compound het, prioritization):

    • Supported patterns: de novo, AD, AR, X-linked (XLR/XLD), compound heterozygous, mitochondrial

    • PED file integration for family-based analysis (--ped, --inheritance-mode)

    • Vectorized compound het detection (10-50x faster than original)

    • Segregation analysis with Fisher’s exact test

    • Pattern prioritization by clinical significance

  • bcftools pre-filtering (--bcftools-prefilter) for early variant filtering during extraction

  • Final filtering (--final-filter) using pandas query syntax on any column including computed scores

  • Sample pseudonymization for privacy-preserving data sharing (Issue #34):

    • Multiple naming schemas: sequential, categorical, anonymous, and custom patterns

    • Consistent pseudonym mapping across all output formats (TSV, Excel, HTML)

    • PED file pseudonymization support (--pseudonymize-ped)

    • Secure mapping table storage in parent directory

  • Checkpoint and resume system for robust pipeline execution:

    • Automatic pipeline state tracking with .variantcentrifuge_state.json

    • Resume capability after interruptions (--enable-checkpoint and --resume)

    • Optional file checksum validation (--checkpoint-checksum)

    • Interactive resume point selection (--interactive-resume)

    • Thread-safe state updates for parallel chunk processing

  • Unified annotation system supporting BED files, gene lists, and JSON gene data

  • JSON gene annotation feature with flexible field mapping (--annotate-json-genes and --json-gene-mapping)

  • Comprehensive Sphinx documentation with modern Furo theme

  • GitHub Actions workflow for automated documentation deployment

  • Tumor-normal filtering presets (somatic, loh, tumor_only) with configurable sample indices and thresholds

  • VCF annotation inspection (--show-vcf-annotations) for field discovery

  • Genotype filtering (--genotype-filter) with per-gene override support

  • Transcript-level filtering (--transcript-list, --transcript-file)

  • ClinVar PM5 annotation support (--clinvar-pm5-lookup)

Changed

  • Documentation migrated from README to structured Sphinx documentation

  • Enhanced filtering with three-stage approach (bcftools pre-filter, SnpSift filter, final filter)

Fixed

  • Numeric type conversion in final filtering to handle mixed data types correctly

  • Gene burden analysis edge cases (Issue #31): Improved handling of infinite and zero odds ratios

[0.5.0] - 2024-08-01

Added

  • Interactive HTML report generation with sortable tables

  • IGV.js integration for genomic visualization

  • Cohort analysis and reporting functionality

  • Gene burden analysis with Fisher’s exact test

  • Phenotype data integration and filtering

  • Preset filter system for common analysis workflows

  • Excel output format support

  • External database links (SpliceAI, Franklin, Varsome, gnomAD, ClinVar)

Changed

  • Improved command-line interface with better argument organization

  • Enhanced configuration system with JSON-based presets

  • Optimized variant filtering pipeline

  • Better error handling and user feedback

Fixed

  • VCF header normalization for indexed fields

  • Sample identification in cohort reports

  • IGV report generation with proper FASTA handling

[0.4.0] - 2024-06-01

Added

  • Comprehensive test suite with pytest

  • Pre-commit hooks for code quality

  • Gene list annotation functionality

  • Variant statistics and metadata generation

Changed

  • Modular code architecture with clear separation of concerns

  • Improved logging and debugging capabilities

  • Enhanced VCF processing pipeline

Fixed

  • Gene BED file generation edge cases

  • Genotype replacement functionality

[0.3.0] - 2024-04-01

Added

  • Gene-centric variant filtering

  • SnpSift integration for field extraction

  • Basic HTML report generation

  • Phenotype integration capabilities

Changed

  • Migrated from Bash/R to Python-based pipeline

  • Improved error handling and validation

[0.2.0] - 2024-02-01

Added

  • Initial Python CLI implementation

  • VCF processing with bcftools integration

  • Basic filtering capabilities

  • Configuration file support

Changed

  • Complete rewrite from shell scripts to Python

[0.1.0] - 2024-01-01

Added

  • Initial release

  • Basic variant filtering functionality

  • Shell script-based pipeline

  • Simple output generation

Legend

  • Added for new features

  • Changed for changes in existing functionality

  • Deprecated for soon-to-be removed features

  • Removed for now removed features

  • Fixed for any bug fixes

  • Security for vulnerability fixes