MrdPersonalizedPanelQcChecker

URS & FS — User Requirements and Functional Specification

This document describes the controlled interface and behaviour of MrdPersonalizedPanelQcChecker for MRD Personalized Panel QC Checker.

Domain limits and critical parameters

• Performs specialized QC of personalized MRD panels per CAP/CLIA, FDA tumor-informed assay guidance and MRD consortium standards: panel design verification (variant count 16–48, 100% tumor match rate, ZERO germline variants, clonal fraction ≥50%, somatic origin confirmation), analytical performance (panel-specific LOD ≤0.01% VAF, mean amplicon depth ≥5000×, uniformity ≥80%, zero failed amplicons), specificity checks (off-target amplification, primer dimers, background noise ≤0.001%), and triple c
• ⚠️ Critical: ANY germline variant in MRD panel = GUARANTEED FALSE POSITIVE at every test. Subclonal-enriched panel risks missing dominant clone at relapse. Without matched normal, somatic/germline distinction is unreliable. Failed amplicons irreversibly reduce sensitivity. LOD must be calculated individually for EACH personalized panel configuration.

URS — User Requirements Specification

input.csv contract

PatientID,PanelID,TumorSequencingID,VariantsInPanel,MinVariantsInPanel,MaxVariantsInPanel,VariantsMatchedToTumor,GermlineVariantsInPanel,ClonalVariants_Count,SubclonalVariants_Count,MinClonalFraction_InPanel,PanelLOD_Percent,MaxAcceptableLOD_Percent,MeanAmpliconDepth_X,MinMeanAmpliconDepth_X,AmpliconUniformity_Percent,MinAmpliconUniformity_Percent,FailedAmplicons_Count,TotalAmplicons_Count,OffTargetAmplification_Detected,PrimerDimer_Detected,BackgroundNoise_VAF,MaxBackgroundNoise_VAF,PositiveControl_Pass,NegativeControl_Pass,NoTemplateControl_Pass,MatchedNormal_Available,SomaticOrigin_Confirmed,TumorVAF_Mean_InPanel
PAT-LUNG-042,MRD-PNL-042-v1,WES-LUNG-042,32,16,48,32,0,24,8,0.5,0.003,0.01,15000,5000,92.0,80,0,32,false,false,0.0002,0.001,true,true,true,true,true,18.5
PAT-CRC-018,MRD-PNL-018-v1,WES-CRC-018,20,16,48,18,3,5,15,0.5,0.015,0.01,3200,5000,65.0,80,4,20,true,true,0.002,0.001,true,true,true,false,false,6.2

Input validation rules

FS — Functional Specification

Example output.json

{
  "utilityId": "mrdpersonalizedpanelqcchecker",
  "utilityFolder": "MrdPersonalizedPanelQcChecker",
  "package": "LiquidBiopsy",
  "overallStatus": "PASS|WARNING|FAIL",
  "sourceFile": "input.csv",
  "processedAtUtc": "2026-06-10T00:00:00Z",
  "checks": [
    {
      "parameter": "PatientID",
      "value": "PAT-LUNG-042",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-001"
    },
    {
      "parameter": "PanelID",
      "value": "MRD-PNL-042-v1",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-002"
    },
    {
      "parameter": "TumorSequencingID",
      "value": "WES-LUNG-042",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-003"
    },
    {
      "parameter": "VariantsInPanel",
      "value": "32",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-004"
    },
    {
      "parameter": "MinVariantsInPanel",
      "value": "16",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-005"
    },
    {
      "parameter": "MaxVariantsInPanel",
      "value": "48",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-006"
    },
    {
      "parameter": "VariantsMatchedToTumor",
      "value": "32",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-007"
    },
    {
      "parameter": "GermlineVariantsInPanel",
      "value": "0",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-008"
    },
    {
      "parameter": "ClonalVariants_Count",
      "value": "24",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-009"
    },
    {
      "parameter": "SubclonalVariants_Count",
      "value": "8",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-010"
    },
    {
      "parameter": "MinClonalFraction_InPanel",
      "value": "0.5",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-011"
    },
    {
      "parameter": "PanelLOD_Percent",
      "value": "0.003",
      "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": "MrdPersonalizedPanelQcChecker.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.