ProteomicSignalAcceptanceChecker

URS & FS — User Requirements and Functional Specification

This document describes the controlled interface and behaviour of ProteomicSignalAcceptanceChecker for Proteomic Signal Acceptance Checker.

Domain limits and critical parameters

• Performs per-measurement quality verification per HUPO-PSI, CPTAC QC guidelines, CAP/CLIA proteomics and FDA biomarker qualification standards: detection status (above/below LOD/LOQ, signal-to-LOD ratio), precision (replicate CV ≤20%, minimum 2 replicates), sample controls (IPCC deviation ≤15%, INC counts, extension control for Olink; platform-specific for SomaLogic/LC-MS), specificity flags (cross-reactivity check), normalization (NPX scale factor 0.5–2.0), biological plausibility (context-depe
• ⚠️ Critical: Between LOD and LOQ = DETECTED but NOT QUANTITATIVELY RELIABLE. Do not use for fold-change. Sample control failure affects ALL proteins in that sample. Specificity flag failure requires orthogonal verification (WB, targeted MS). NPX scale factor outside range indicates sample-level issue. Biological ranges are matrix-dependent. Edge effects may be systematic. Tool assesses TECHNICAL QUALITY of individual signal; biological interpretation requires clinical context integration. FLAGGE

URS — User Requirements Specification

input.csv contract

SampleID,ProteinTarget,UniProtID,Platform,AssayPanel,RawSignal_NPX_or_RFU,NormalizedValue,Units,LOD_Value,LOQ_Value,AboveLOD,AboveLOQ,SignalToLOD_Ratio,NumTechnicalReplicates,ReplicateCV_Percent,MaxReplicateCV_Percent,ReplicateMean,ReplicateSD,IPCC_Deviation_Percent,MaxIPCC_Deviation_Percent,INC_CountsPerSec,MinINC_CountsPerSec,ExtensionControl_Counts,MinExtensionControl_Counts,SampleControls_Pass,SpecificityFlag_Pass,OutlierFlag_Raised,NPX_ScaleFactor,MinNPX_ScaleFactor,MaxNPX_ScaleFactor,ExpectedRange_Low,ExpectedRange_High,WithinBiologicalRange,TissueContext,PlateID,WellPosition,IsPlateEdge,ReagentLot
PL-042,IL6,P05231,Olink_Explore,Inflammation_92,8.45,8.45,NPX,0.12,0.45,true,true,70.4,2,4.2,20,8.45,0.35,3.5,15,850,100,2500,500,true,true,false,1.02,0.5,2.0,0.5,15.0,true,Plasma,PLT-2026-089,D6,false,OLK-2026-089
PL-055,TNFRSF1A,P19438,Olink_Explore,Inflammation_92,0.38,0.38,NPX,0.15,0.52,true,false,2.5,2,28.5,20,0.38,0.108,18.2,15,95,100,420,500,false,true,true,0.42,0.5,2.0,1.0,12.0,false,Plasma,PLT-2026-090,A1,true,OLK-2026-090
PL-061,MMP9,P14780,SomaLogic,Cardiovascular_200,1250,1180,RFU,50,180,true,true,25.0,3,8.5,20,1250,106,5.0,15,0,0,0,0,true,false,false,1.05,0.5,2.0,200,5000,true,Serum,SL-2026-045,F8,false,SL-2026-112

Input validation rules

FS — Functional Specification

Example output.json

{
  "utilityId": "proteomicsignalacceptancechecker",
  "utilityFolder": "ProteomicSignalAcceptanceChecker",
  "package": "LiquidBiopsy",
  "overallStatus": "PASS|WARNING|FAIL",
  "sourceFile": "input.csv",
  "processedAtUtc": "2026-06-10T00:00:00Z",
  "checks": [
    {
      "parameter": "SampleID",
      "value": "PL-042",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-001"
    },
    {
      "parameter": "ProteinTarget",
      "value": "IL6",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-002"
    },
    {
      "parameter": "UniProtID",
      "value": "P05231",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-003"
    },
    {
      "parameter": "Platform",
      "value": "Olink_Explore",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-004"
    },
    {
      "parameter": "AssayPanel",
      "value": "Inflammation_92",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-005"
    },
    {
      "parameter": "RawSignal_NPX_or_RFU",
      "value": "8.45",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-006"
    },
    {
      "parameter": "NormalizedValue",
      "value": "8.45",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-007"
    },
    {
      "parameter": "Units",
      "value": "NPX",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-008"
    },
    {
      "parameter": "LOD_Value",
      "value": "0.12",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-009"
    },
    {
      "parameter": "LOQ_Value",
      "value": "0.45",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-010"
    },
    {
      "parameter": "AboveLOD",
      "value": "true",
      "status": "PASS|WARNING|FAIL",
      "message": "Deterministic rule-based check result",
      "ruleReference": "FS-RULE-011"
    },
    {
      "parameter": "AboveLOQ",
      "value": "true",
      "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": "ProteomicSignalAcceptanceChecker.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.