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name: 'myeloma-mrd-agent' description: 'AI-powered minimal residual disease (MRD) analysis for multiple myeloma using next-generation flow cytometry, NGS, and mass spectrometry approaches.' measurable_outcome: Execute skill workflow successfully with valid output within 15 minutes. allowed-tools:

  • read_file
  • run_shell_command

Myeloma MRD Agent

The Myeloma MRD Agent provides comprehensive AI-driven minimal residual disease assessment for multiple myeloma. It integrates next-generation flow cytometry (NGF), NGS-based clonotype tracking, and mass spectrometry M-protein detection for ultra-sensitive MRD monitoring.

When to Use This Skill

  • When assessing MRD status in multiple myeloma patients post-treatment.
  • To select optimal MRD testing modality (NGF vs NGS vs MS).
  • For predicting progression-free survival based on MRD kinetics.
  • When integrating MRD with other response criteria (IMWG).
  • To guide treatment intensification or de-escalation decisions.

Core Capabilities

  1. NGF Analysis: AI-enhanced next-generation flow cytometry for MRD detection at 10^-5 to 10^-6 sensitivity.

  2. NGS Clonotype Tracking: Analyze IGH/IGK/IGL rearrangements for molecular MRD.

  3. Mass Spectrometry: MALDI-TOF or LC-MS/MS for M-protein detection.

  4. Multi-Modal Integration: Combine modalities for comprehensive MRD assessment.

  5. Kinetic Modeling: Track MRD dynamics and predict outcomes.

  6. Response Classification: Apply IMWG MRD criteria.

MRD Detection Methods

Method Sensitivity Sample Advantages
NGF (EuroFlow) 10^-5 to 10^-6 BM Standardized, fast
NGS (clonoSEQ) 10^-6 BM Ultra-sensitive
ASO-qPCR 10^-5 BM Quantitative
PET-CT N/A Whole body Extramedullary
MS (MALDI/LC-MS) 10^-5 Serum Non-invasive

IMWG MRD Response Criteria

Category Definition
MRD-negative (10^-5) No clonal plasma cells by NGF or NGS at 10^-5
MRD-negative (10^-6) No clonal plasma cells at 10^-6 sensitivity
Sustained MRD-neg MRD-neg confirmed ≥1 year apart
Flow MRD-neg NGF negative, sensitivity ≥10^-5
Sequencing MRD-neg NGS negative, sensitivity ≥10^-5

Workflow

  1. Input: Flow cytometry FCS files, NGS clonotype data, M-protein MS data, clinical parameters.

  2. NGF Analysis: AI-assisted gating and aberrant plasma cell identification.

  3. NGS Analysis: Clonotype frequency calculation and threshold application.

  4. MS Analysis: M-protein peak detection and quantification.

  5. Integration: Combine multi-modal MRD data.

  6. Kinetics: Model MRD trajectory and predict outcomes.

  7. Output: MRD status, response category, prognostic estimate.

Example Usage

User: "Analyze MRD status for this myeloma patient using flow and NGS data."

Agent Action:

python3 Skills/Hematology/Myeloma_MRD_Agent/myeloma_mrd.py \
    --flow_fcs bone_marrow_ngf.fcs \
    --ngs_clonotype clonoseq_results.json \
    --ms_mprotein maldi_spectrum.csv \
    --baseline_clone diagnosis_clone.json \
    --treatment_phase post_consolidation \
    --output mrd_report.json

NGF Panel (EuroFlow-Based)

Tube 1: CD138/CD38/CD45/CD19/CD56/CD27/CD81/CD117

Aberrant Plasma Cell Phenotype:

  • CD138+, CD38++
  • CD19- or dim (normal PC: CD19+)
  • CD56+ (normal PC: CD56-)
  • CD45- or dim (normal PC: CD45+)
  • CD27- or dim
  • CD117+ (often aberrant)

AI-Assisted Flow Cytometry

Automated Gating:

  • CNN-based plasma cell identification
  • Aberrant vs normal PC discrimination
  • Consistent quantification across samples

Quality Control:

  • Sample adequacy assessment
  • Hemodilution detection
  • Event count validation

NGS Clonotype Analysis

Process:

  1. Identify dominant clone at diagnosis (IGH/IGK/IGL)
  2. Design clone-specific assay or use multiplex (clonoSEQ)
  3. Track clonal frequency in follow-up samples
  4. Apply MRD threshold (typically 10^-5 or 10^-6)

Considerations:

  • Clonal evolution may affect tracking
  • Biclonal disease requires tracking both
  • IGK/IGL backup if IGH fails

Prognostic Significance

MRD Status PFS HR OS HR
MRD-neg (10^-5) 0.35-0.45 0.40-0.50
MRD-neg (10^-6) 0.25-0.35 0.30-0.40
Sustained MRD-neg 0.20-0.30 0.25-0.35

Clinical Decision Support

MRD-Guided Treatment:

  • De-escalation in sustained MRD-neg
  • Intensification if MRD conversion
  • Maintenance duration decisions

Monitoring Frequency:

  • Post-induction
  • Post-consolidation
  • Post-transplant (Day +100)
  • Every 6-12 months on maintenance

Prerequisites

  • Python 3.10+
  • FlowJo or equivalent for FCS files
  • NGS analysis pipelines
  • Mass spectrometry processing tools

Related Skills

  • Flow_Cytometry_AI - For general flow analysis
  • Multiple_Myeloma_AI - For disease-specific analysis
  • Liquid_Biopsy_Analytics_Agent - For ctDNA approaches

Emerging Methods

  1. Circulating tumor cells: Blood-based PC detection
  2. Cell-free DNA: Myeloma-specific mutations
  3. Imaging: PET/MRI for extramedullary disease
  4. Serum-based NGS: M-protein sequencing

Author

AI Group - Biomedical AI Platform