PanelCoverageQcChecker

URS & FS — User Requirements and Functional Specification

This document describes the controlled interface and behaviour of PanelCoverageQcChecker for Panel Coverage QC Checker.

Domain limits and critical parameters

• Performs region-level coverage evaluation per CAP/CLIA, FDA NGS guidance, AMP/ASCO/CAP and SEQC2 standards: base coverage (≥95% bases above min depth), uniformity (≥80%, fold-80 penalty ≤2.0×, blind spot fraction ≤2%), clinically critical parameters (ZERO blind spots in actionable regions, 100% clinical genes fully covered, all known problematic regions addressed), systematic biases (GC correlation |r|≤0.3, high/low-GC affected regions, off-target rate ≤20%, repeat masking, segmental duplication
• ⚠️ Critical: Mean depth does NOT guarantee all-region coverage. Single blind spot in critical gene = INSUFFICIENT. GC bias >0.3 indicates systematic enrichment/design issue. Fold-80 >2.0 means disproportionate resequencing needed. Known problematic regions must be DOCUMENTED. Off-target >20% reduces effective depth. Tool assesses TECHNICAL COVERAGE only; does not replace empirical LoD verification per variant/region. Coverage ≥100× is necessary but not sufficient for guaranteed LoD.

URS — User Requirements Specification

input.csv contract

RunID,PanelName,PanelVersion,Platform,MeanTargetDepth_X,MedianTargetDepth_X,MinTargetDepth_X,RequiredMinDepth_X,PercentBases_Above_MinDepth,MinPercentBases_Above_MinDepth,Uniformity_Percent,MinUniformity_Percent,Fold80_BasePenalty,MaxFold80,TotalTargetRegions,RegionsBelowMinDepth,CriticalRegionsBelowMinDepth,TotalCriticalRegions,MaxAllowedBlindSpot_Fraction,GCCorrelation_Coefficient,MaxGCCorrelation,HighGC_Regions_BelowThreshold_Count,LowGC_Regions_BelowThreshold_Count,KnownProblematicRegions_Total,KnownProblematicRegions_Covered,UncoveredProblematicRegions,ClinicalGenes_Total,ClinicalGenes_FullyCovered,PartiallyCoveredGenes,OffTargetRate_Percent,MaxOffTargetRate_Percent,RepeatMasking_Applied,SegmentalDuplication_Flagged
COV-2026-001,OncoPanel_500,v4.2,NovaSeq,850,820,120,100,98.5,95,93.0,80,1.3,2.0,5200,78,0,450,0.02,0.12,0.3,15,8,25,25,,50,50,,8.5,20,true,true
COV-2026-002,HemePanel_300,v2.1,NextSeq,450,380,15,100,82.0,95,68.0,80,3.5,2.0,3100,558,12,280,0.02,0.55,0.3,185,92,18,10,FLT3_ITD;CEBPA_TAD;NPM1_exon12,40,35,FLT3;CEBPA;DNMT3A;TET2;ASXL1,22.0,20,false,false

Input validation rules

FS — Functional Specification

Example output.json

{
  "utilityId": "panelcoverageqcchecker",
  "utilityFolder": "PanelCoverageQcChecker",
  "package": "LiquidBiopsy",
  "overallStatus": "PASS|WARNING|FAIL",
  "sourceFile": "input.csv",
  "processedAtUtc": "2026-06-10T00:00:00Z",
  "checks": [
    {
      "parameter": "RunID",
      "value": "COV-2026-001",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-001"
    },
    {
      "parameter": "PanelName",
      "value": "OncoPanel_500",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-002"
    },
    {
      "parameter": "PanelVersion",
      "value": "v4.2",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-003"
    },
    {
      "parameter": "Platform",
      "value": "NovaSeq",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-004"
    },
    {
      "parameter": "MeanTargetDepth_X",
      "value": "850",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-005"
    },
    {
      "parameter": "MedianTargetDepth_X",
      "value": "820",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-006"
    },
    {
      "parameter": "MinTargetDepth_X",
      "value": "120",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-007"
    },
    {
      "parameter": "RequiredMinDepth_X",
      "value": "100",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-008"
    },
    {
      "parameter": "PercentBases_Above_MinDepth",
      "value": "98.5",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-009"
    },
    {
      "parameter": "MinPercentBases_Above_MinDepth",
      "value": "95",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-010"
    },
    {
      "parameter": "Uniformity_Percent",
      "value": "93.0",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-011"
    },
    {
      "parameter": "MinUniformity_Percent",
      "value": "80",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-012"
    }
  ],
  "criticalFindings": [],
  "warnings": [],
  "audit": {
    "inputHash": "sha256:<calculated at runtime>",
    "rulesVersion": "<utility executable version>",
    "documentation": "PanelCoverageQcChecker.documentation.html"
  }
}

Traceability matrix

IQ/OQ/PQ test scenarios

QA/QC and change control

• Do not rename columns without updating validator, documentation and test set.
• Retain input.csv, output.json, executable version and checksum.
• Before production use, perform IQ/OQ/PQ or equivalent CSV/CSA verification.
• Critical limits shall be verified against the approved specification, registration dossier and local SOPs.
• The utility provides structured QC decision support; final release decision remains with QA/QP and approved procedures.