Subworkflows

CheckRef is organized as a single cohesive workflow without separate subworkflows. All processes are directly integrated into the main workflow for simplicity and ease of maintenance.

Main Workflow Components

The pipeline consists of the following main process groups:

1. Validation Processes

• VALIDATE_VCF: Checks VCF file integrity and format
• Ensures files are not empty, corrupted, or malformed
• Validates required VCF headers and structure

2. Detection Processes

• DETECT_CHROMOSOME: Automatically identifies chromosome from filename
• MATCH_VCF_TO_LEGEND: Pairs VCF files with corresponding reference legend files
• Handles various chromosome naming conventions

3. Analysis Processes

• CHECK_ALLELE_SWITCH: Core allele switch detection
• Compares REF/ALT alleles between target and reference
• Identifies MATCH, SWITCH, COMPLEMENT, and OTHER categories

4. Correction Processes

Two mutually exclusive correction methods:

REMOVE_SWITCHED_SITES:

• Removes variants with allele switches
• Creates cleaned VCF files
• Preserves only matching variants

CORRECT_SWITCHED_SITES:

• Swaps REF↔ALT alleles at switched sites
• Adds SWITCHED=1 flag to INFO field
• Maintains all variants while fixing orientation

5. Verification Processes

• VERIFY_CORRECTIONS: Validates that corrections were applied correctly
• Re-runs allele switch detection on corrected files
• Ensures no remaining switches in output

6. Aggregation Processes

• CREATE_SUMMARY: Combines per-chromosome results
• Generates aggregate statistics across all chromosomes
• Produces final summary reports

Process Dependencies

The workflow follows this dependency chain:

VALIDATE_VCF
    ↓
DETECT_CHROMOSOME
    ↓
MATCH_VCF_TO_LEGEND
    ↓
CHECK_ALLELE_SWITCH
    ↓
[REMOVE_SWITCHED_SITES OR CORRECT_SWITCHED_SITES]
    ↓
VERIFY_CORRECTIONS
    ↓
CREATE_SUMMARY

Parallel Processing

Multiple VCF files are processed in parallel through the workflow, with Nextflow automatically managing:

• Process scheduling
• Resource allocation
• Data flow between processes
• Error handling and retry logic

Future Enhancements

Potential subworkflow candidates for future refactoring:

• QC Subworkflow: Quality control and validation steps
• Detection Subworkflow: Chromosome detection and matching
• Correction Subworkflow: Allele switch fixing logic
• Reporting Subworkflow: Summary generation and visualization