RecurrenceSignalGateChecker

URS & FS — User Requirements and Functional Specification

This document describes the controlled interface and behaviour of RecurrenceSignalGateChecker for Recurrence Signal Gate Checker.

Domain limits and critical parameters

• Performs cascaded verification of MRD recurrence signals per ESMO MRD Guidelines, NCCN Surveillance, CAP/CLIA and TRACERx standards: technical validity (above LOD, S/LOD ≥3.0, supporting reads ≥3, UMI families ≥3), artifact exclusion (CHIP filter, germline exclusion, index hopping, strand bias, homopolymer, PoN, background noise), confirmation evidence (repeat test concordance, orthogonal method, consecutive positives ≥2), kinetics assessment (rising trend, biologically plausible doubling time 1
• ⚠️ Critical: Cost of FP in recurrence screening = unnecessary toxic therapy + psychological harm. Cost of FN = missed curability window. Single detection without confirmation IS NOT basis for clinical action. CHIP variants account for up to 30% of false-positive MRD signals in patients >60. Molecular lead time (MRD+/Imaging-) averages 2–6 months. Action decisions made by MULTIDISCIPLINARY TEAM, not automatically. For asymptomatic MRD+ patients, confirmation recommended BEFORE therapy initiation.

URS — User Requirements Specification

input.csv contract

PatientID,PrimaryTumorType,AssayName,ClinicalContext,LastCurativeTreatment_Date,MonthsSinceTreatment,DetectedVariant,CurrentVAF_Percent,AssayLOD_Percent,SignalToLOD_Ratio,SupportingReads,MinSupportingReads,UniqueMolecularFamilies,MinUniqueFamilies,RepeatTest_Performed,RepeatTest_Concordant,RepeatTest_VAF_Percent,DaysBetweenTests,OrthogonalMethod_Confirmation,OrthogonalMethod_Concordant,PriorNegativeResults_Count,PriorBaseline_VAF_Percent,RisingTrend_Detected,DoublingTime_Days,MinDoublingTime_Plusible_Days,MaxDoublingTime_Plusible_Days,ConsecutivePositive_Count,IsKnownCHIP_Variant,CHIP_Filter_Applied,GermlineVariant_Excluded,IndexHopping_Filtered,StrandBias_Detected,HomopolymerRegion_Variant,InPanelOfNormals,BackgroundNoise_AtPosition_VAF,MaxBackgroundNoise_VAF,VariantMatches_PrimaryTumor,TissueOfOrigin_Plausible,NewVariant_NotInPrimary,LastImaging_Date,LastImaging_Result,DaysSinceLastImaging,UnscheduledImaging_Performed,UnscheduledImaging_Result,Symptoms_Present,ECOG_Status,ActionableTherapy_Available
REC-PAT-001,NSCLC,Signatera_NSCLC,Post_Curative_Treatment,2025-08-15,10,EGFR_L858R,0.08,0.01,8.0,45,3,12,3,true,true,0.12,14,false,false,3,12.5,true,35,14,365,2,false,true,true,true,false,false,false,0.0002,0.005,true,true,,2026-05-20,NED,25,false,,false,0,true
REC-PAT-002,CRC,Guardant_Reveal,Adjuvant_Monitoring,2025-12-01,6,DNMT3A_R882H,0.03,0.01,3.0,8,3,4,3,true,false,0.0,21,false,false,2,0,false,0,14,365,1,true,false,true,true,false,false,false,0.001,0.005,false,false,DNMT3A_R882H,2026-05-15,NED,30,false,,false,0,false
REC-PAT-003,Breast,RaDaR_Breast,Active_Surveillance,2025-06-20,12,PIK3CA_H1047R,0.02,0.01,2.0,5,3,3,3,false,false,0,0,false,false,4,8.0,false,0,14,365,1,false,true,true,true,false,false,false,0.0003,0.005,true,true,,2026-06-01,NED,14,false,,false,0,true

Input validation rules

FS — Functional Specification

Example output.json

{
  "utilityId": "recurrencesignalgatechecker",
  "utilityFolder": "RecurrenceSignalGateChecker",
  "package": "LiquidBiopsy",
  "overallStatus": "PASS|WARNING|FAIL",
  "sourceFile": "input.csv",
  "processedAtUtc": "2026-06-10T00:00:00Z",
  "checks": [
    {
      "parameter": "PatientID",
      "value": "REC-PAT-001",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-001"
    },
    {
      "parameter": "PrimaryTumorType",
      "value": "NSCLC",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-002"
    },
    {
      "parameter": "AssayName",
      "value": "Signatera_NSCLC",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-003"
    },
    {
      "parameter": "ClinicalContext",
      "value": "Post_Curative_Treatment",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-004"
    },
    {
      "parameter": "LastCurativeTreatment_Date",
      "value": "2025-08-15",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-005"
    },
    {
      "parameter": "MonthsSinceTreatment",
      "value": "10",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-006"
    },
    {
      "parameter": "DetectedVariant",
      "value": "EGFR_L858R",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-007"
    },
    {
      "parameter": "CurrentVAF_Percent",
      "value": "0.08",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-008"
    },
    {
      "parameter": "AssayLOD_Percent",
      "value": "0.01",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-009"
    },
    {
      "parameter": "SignalToLOD_Ratio",
      "value": "8.0",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-010"
    },
    {
      "parameter": "SupportingReads",
      "value": "45",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-011"
    },
    {
      "parameter": "MinSupportingReads",
      "value": "3",
      "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": "RecurrenceSignalGateChecker.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.