OncologyCfdnaCgpChecker

URS & FS — User Requirements and Functional Specification

This document describes the controlled interface and behaviour of OncologyCfdnaCgpChecker for Oncology cfDNA CGP Checker.

Domain limits and critical parameters

• Performs end-to-end quality verification of cfDNA CGP panels per NCCN, ESMO Precision Medicine, CAP/CLIA, FDA CDx guidance and AMP/ASCO/CAP Tiering standards: pre-analytical cfDNA QC (yield ≥10ng, fragment profile, hemolysis ≤50), analytical metrics (mean depth ≥10,000×, UMI depth ≥1,000×, on-target ≥60%, uniformity ≥80%, duplication ≤60%), mandatory coverage of 12 critical genes (EGFR, ALK, ROS1, BRAF, MET ex14, RET, NTRK, KRAS G12C, ERBB2, PIK3CA, BRCA1/2) plus MSI and TMB assessment, sensitiv
• ⚠️ Critical: Missing ANY of 12 critical genes = INVALID for therapeutic decisions. UMI depth <1,000× makes VAF <0.5% detection unreliable. Without CHIP filter, DNMT3A/TET2/ASXL1 variants may be misattributed to tumor. MSI-H/TMB-H have direct therapeutic implications; omission is unacceptable. Negative cfDNA CGP does NOT rule out actionable variants; tissue biopsy may be necessary. Results must include AMP Tier classification and specific therapy recommendations. Tool assesses TECHNICAL QUALITY a

URS — User Requirements Specification

input.csv contract

SampleID,PatientID,PrimaryTumorType,PanelName,ClinicalContext,CfDNA_Yield_ng,MinCfDNA_Yield_ng,FragmentSize_Peak_bp,FragmentProfile_Valid,HemolysisIndex,MaxHemolysisIndex,MeanTargetDepth_X,MinMeanTargetDepth_X,UniqueMolecularDepth_X,MinUniqueMolecularDepth_X,OnTargetRate_Percent,MinOnTargetRate_Percent,Uniformity_Percent,MinUniformity_Percent,DuplicationRate_Percent,MaxDuplicationRate_Percent,AssayLOD_SNv_Percent,AssayLOD_Indel_Percent,AssayLOD_Fusion_Percent,AssayLOD_CNV_FoldChange,BackgroundNoise_VAF,MaxBackgroundNoise_VAF,CriticalGenes_Total,CriticalGenes_Covered,EGFR_Covered,ALK_Covered,ROS1_Covered,BRAF_Covered,MET_Exon14_Covered,RET_Covered,NTRK_Covered,KRAS_G12C_Covered,ERBB2_Covered,PIK3CA_Covered,BRCA1_2_Covered,MSI_Status_Assessed,TMB_Assessed,PositiveControl_Pass,NegativeControl_Pass,NoTemplateControl_Pass,InternalAmplification_Control_Pass,ActionableVariants_Detected,DetectedVariants_Summary,TherapyRecommendations,AmpTier_Level,MSiHigh,TMB_Score,TMB_High,GermlineFilter_Applied,ClonalHematopoiesis_Filter_Applied,IndexHopping_Filter_Applied
CFDNA-CGP-2026-001,PAT-LUNG-042,NSCLC,FoundationOne_Liquid,Resistance,32.0,10,167,true,8,50,22000,10000,4800,1000,78.0,60,91.0,80,28.0,60,0.1,0.2,0.5,2.0,0.0003,0.001,12,12,true,true,true,true,true,true,true,true,true,true,true,true,true,true,true,true,2,EGFR:L858R;MET:amplification,Osimertinib+Capmatinib;Clinical_Trial_NCT05123456,Tier I,false,8.5,false,true,true,true
CFDNA-CGP-2026-002,PAT-CRC-055,CRC,Guardant360,First_Line,6.0,10,165,true,62,50,5500,10000,450,1000,52.0,60,68.0,80,72.0,60,0.1,0.2,0.5,2.0,0.0025,0.001,12,9,true,true,true,true,false,true,false,true,true,true,false,true,false,true,true,true,1,KRAS:G12C,Sotorasib (if confirmed),Tier I,false,0,false,true,false,true
CFDNA-CGP-2026-003,PAT-BRCA-061,Breast,Tempus_xF,Screening,25.0,10,168,true,5,50,18000,10000,3500,1000,82.0,60,89.0,80,22.0,60,0.1,0.2,0.5,2.0,0.0002,0.001,12,12,true,true,true,true,true,true,true,true,true,true,true,true,true,true,true,true,0,None,Consider tissue biopsy if clinically indicated,N/A,false,4.2,false,true,true,true

Input validation rules

FS — Functional Specification

Example output.json

{
  "utilityId": "oncologycfdnacgpchecker",
  "utilityFolder": "OncologyCfdnaCgpChecker",
  "package": "LiquidBiopsy",
  "overallStatus": "PASS|WARNING|FAIL",
  "sourceFile": "input.csv",
  "processedAtUtc": "2026-06-10T00:00:00Z",
  "checks": [
    {
      "parameter": "SampleID",
      "value": "CFDNA-CGP-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": "PrimaryTumorType",
      "value": "NSCLC",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-003"
    },
    {
      "parameter": "PanelName",
      "value": "FoundationOne_Liquid",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-004"
    },
    {
      "parameter": "ClinicalContext",
      "value": "Resistance",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-005"
    },
    {
      "parameter": "CfDNA_Yield_ng",
      "value": "32.0",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-006"
    },
    {
      "parameter": "MinCfDNA_Yield_ng",
      "value": "10",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-007"
    },
    {
      "parameter": "FragmentSize_Peak_bp",
      "value": "167",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-008"
    },
    {
      "parameter": "FragmentProfile_Valid",
      "value": "true",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-009"
    },
    {
      "parameter": "HemolysisIndex",
      "value": "8",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-010"
    },
    {
      "parameter": "MaxHemolysisIndex",
      "value": "50",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-011"
    },
    {
      "parameter": "MeanTargetDepth_X",
      "value": "22000",
      "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": "OncologyCfdnaCgpChecker.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.