LungCancerLiquidBiopsyQcChecker

URS & FS — User Requirements and Functional Specification

This document describes the controlled interface and behaviour of LungCancerLiquidBiopsyQcChecker for Lung Cancer Liquid Biopsy QC Checker.

Domain limits and critical parameters

• Comprehensive QC for NSCLC liquid biopsy per NCCN, ESMO, CAP/CLIA and FDA CDx guidance: pre-analytical (cfDNA yield, fragment profile), analytical (depth ≥10,000×, UMI depth ≥1,000×, on-target ≥60%, uniformity ≥80%), mandatory coverage of 9 NCCN-critical genes (EGFR, ALK, ROS1, BRAF, MET exon14, RET, NTRK, KRAS G12C, ERBB2), triple control verification, context-aware clinical interpretation (primary diagnosis/monitoring/resistance), and automatic resistance mechanism detection. Four-tier classif
• ⚠️ Critical: Missing ANY of 9 NCCN genes = INVALID. No drivers in primary diagnosis = recommend tissue biopsy. Resistance mechanism = immediate therapy review per NCCN. All controls must PASS.

URS — User Requirements Specification

input.csv contract

SampleID,PatientID,ClinicalContext,CfDNA_Yield_ng,MinCfDNA_Yield_ng,FragmentSize_Peak_bp,FragmentProfile_Valid,MeanTargetDepth_X,MinMeanTargetDepth_X,UniqueMolecularDepth_X,MinUniqueMolecularDepth_X,OnTargetRate_Percent,MinOnTargetRate_Percent,Uniformity_Percent,MinUniformity_Percent,EGFR_Covered,ALK_Covered,ROS1_Covered,BRAF_Covered,MET_Exon14_Covered,RET_Covered,NTRK_Covered,KRAS_G12C_Covered,ERBB2_Covered,InternalControl_Pass,NTC_Pass,PositiveControl_Pass,DriverMutations_Detected,DetectedVariants,ResistanceMechanism_Detected,ResistanceVariant,MaxVAF_Detected_Percent,AssayLOD_Percent,CurrentTherapy,TherapyMatch_Variant
NSCLC-LB-2026-001,PAT-LUNG-042,Resistance_Detection,35.0,10,167,true,25000,10000,4500,1000,85.0,60,92.0,80,true,true,true,true,true,true,true,true,true,true,true,true,2,EGFR:L858R;MET:amplification,true,MET:amplification,3.2,0.1,Osimertinib,true
NSCLC-LB-2026-002,PAT-LUNG-055,Primary_Diagnosis,5.0,10,165,true,8000,10000,600,1000,55.0,60,72.0,80,true,true,true,true,false,true,true,true,true,true,true,true,0,,false,,0,0.1,,false
NSCLC-LB-2026-003,PAT-LUNG-061,Primary_Diagnosis,22.0,10,168,true,18000,10000,3200,1000,78.0,60,88.0,80,true,true,true,true,true,true,true,true,true,true,true,true,0,,false,,0,0.1,,false

Input validation rules

FS — Functional Specification

Example output.json

{
  "utilityId": "lungcancerliquidbiopsyqcchecker",
  "utilityFolder": "LungCancerLiquidBiopsyQcChecker",
  "package": "LiquidBiopsy",
  "overallStatus": "PASS|WARNING|FAIL",
  "sourceFile": "input.csv",
  "processedAtUtc": "2026-06-10T00:00:00Z",
  "checks": [
    {
      "parameter": "SampleID",
      "value": "NSCLC-LB-2026-001",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-001"
    },
    {
      "parameter": "PatientID",
      "value": "PAT-LUNG-042",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-002"
    },
    {
      "parameter": "ClinicalContext",
      "value": "Resistance_Detection",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-003"
    },
    {
      "parameter": "CfDNA_Yield_ng",
      "value": "35.0",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-004"
    },
    {
      "parameter": "MinCfDNA_Yield_ng",
      "value": "10",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-005"
    },
    {
      "parameter": "FragmentSize_Peak_bp",
      "value": "167",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-006"
    },
    {
      "parameter": "FragmentProfile_Valid",
      "value": "true",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-007"
    },
    {
      "parameter": "MeanTargetDepth_X",
      "value": "25000",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-008"
    },
    {
      "parameter": "MinMeanTargetDepth_X",
      "value": "10000",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-009"
    },
    {
      "parameter": "UniqueMolecularDepth_X",
      "value": "4500",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-010"
    },
    {
      "parameter": "MinUniqueMolecularDepth_X",
      "value": "1000",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-011"
    },
    {
      "parameter": "OnTargetRate_Percent",
      "value": "85.0",
      "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": "LungCancerLiquidBiopsyQcChecker.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.