Agent skill

tcr-repertoire-analysis-agent

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Install this agent skill to your Project

npx add-skill https://github.com/majiayu000/claude-skill-registry/tree/main/skills/data/tcr-repertoire-analysis-agent

SKILL.md

---name: tcr-repertoire-analysis-agent description: AI-powered T-cell receptor repertoire analysis for cancer diagnosis, immunotherapy response prediction, and therapeutic TCR selection using deep learning and multi-layer ML approaches. license: MIT metadata: author: AI Group version: "1.0.0" created: "2026-01-20" compatibility:

  • system: Python 3.10+ allowed-tools:
  • run_shell_command
  • read_file
  • write_file

keywords:

  • tcr-repertoire-analysis-agent
  • automation
  • biomedical measurable_outcome: execute task with >95% success rate. ---"

TCR Repertoire Analysis Agent

The TCR Repertoire Analysis Agent provides comprehensive T-cell receptor repertoire analysis for cancer immunology applications. It leverages deep learning and multi-layer machine learning approaches to analyze TCR diversity, predict immunotherapy response, identify tumor-reactive TCRs, and support therapeutic TCR selection for cancer immunotherapy.

When to Use This Skill

  • When analyzing TCR repertoire for cancer diagnosis and staging.
  • For predicting immunotherapy (anti-PD-1/PD-L1) response from TCR profiles.
  • To identify tumor-reactive TCRs for adoptive cell therapy.
  • When monitoring treatment response through TCR clonality changes.
  • For selecting therapeutic TCRs for TCR-T cell therapy development.

Core Capabilities

  1. Repertoire Diversity Analysis: Quantify TCR diversity, clonality, and convergence.

  2. Cancer Diagnosis: Distinguish cancer types from TCR signatures.

  3. Immunotherapy Response Prediction: Predict checkpoint inhibitor response.

  4. Tumor-Reactive TCR Identification: Find neoantigen-specific TCRs.

  5. TCR-pMHC Binding Prediction: Predict TCR epitope specificity.

  6. Clonal Dynamics Tracking: Monitor TCR clones during treatment.

TCR Repertoire Metrics

Metric Definition Clinical Significance
Clonality Gini coefficient of clone sizes Immune focusing
Shannon Entropy Diversity measure Immune breadth
Richness Unique clonotypes Repertoire depth
Top Clone % Largest clone fraction Dominant response
Convergent TCRs Shared across patients Public epitope response
Tumor-Infiltrating % TIL-derived TCRs Tumor reactivity

Workflow

  1. Input: TCR-seq data (bulk or single-cell), clinical metadata.

  2. Preprocessing: CDR3 extraction, error correction, clustering.

  3. Repertoire Analysis: Calculate diversity, clonality, convergence.

  4. ML Classification: Cancer type, stage, response prediction.

  5. TCR Prioritization: Rank tumor-reactive TCR candidates.

  6. TCR-pMHC Prediction: Predict epitope specificity.

  7. Output: Repertoire metrics, predictions, therapeutic candidates.

Example Usage

User: "Analyze the TCR repertoire from this melanoma patient's tumor and blood to predict immunotherapy response and identify tumor-reactive TCRs."

Agent Action:

bash
python3 Skills/Immunology_Vaccines/TCR_Repertoire_Analysis_Agent/tcr_repertoire_analysis.py \
    --tumor_tcr tumor_tils.tsv \
    --blood_tcr pbmc_tcrs.tsv \
    --cancer_type melanoma \
    --hla_type HLA-A*02:01,HLA-B*07:02 \
    --neoantigens patient_neoantigens.fasta \
    --task response_prediction,tcr_identification \
    --output tcr_analysis/

Input Formats

Format Source Fields
AIRR-seq Standardized CDR3, V/J genes, count
MiXCR MiXCR pipeline Clone info, counts
10x VDJ Single-cell CDR3, cell barcode
Custom TSV Any pipeline Flexible mapping

Output Components

Output Description Format
Repertoire Metrics Diversity scores .json
Response Prediction Immunotherapy probability .json
Cancer Classification Type/stage prediction .json
Tumor-Reactive TCRs Ranked candidates .csv
TCR-pMHC Predictions Epitope specificity .csv
Clonal Tracking Dynamics over time .csv
Visualizations Repertoire plots .png, .pdf

Response Prediction Features

Feature Category Features Importance
Diversity Shannon, Gini, richness High
Clonality Top clones, expansion High
Convergence Public TCRs, sharing Moderate
Sequence Features CDR3 length, motifs Moderate
TIL Characteristics TIL fraction, phenotype High

AI/ML Components

Cancer Classification:

  • Multi-layer ensemble (XGBoost, RF, SVM)
  • TCR embedding networks
  • Attention-based sequence models

Response Prediction:

  • Cox regression with TCR features
  • Deep survival analysis
  • Multi-task learning (response + survival)

TCR-pMHC Prediction:

  • AlphaFold3-based structural prediction
  • Transformer models (TCR-BERT)
  • Contrastive learning embeddings

Clinical Applications

Application TCR Biomarker Clinical Utility
Diagnosis Cancer-specific TCRs Early detection
Staging Clonality patterns Disease extent
Prognosis Intratumoral diversity Survival prediction
Response Baseline clonality IO response
Monitoring Clone dynamics Treatment tracking
Therapy Tumor-reactive TCRs TCR-T development

Performance Benchmarks

Task Dataset Performance
Cancer vs Normal Digestive cancers AUC 0.91
Metastasis Detection CRC AUC 0.85
IO Response Melanoma AUC 0.78
TCR-pMHC Prediction IEDB benchmark AUC 0.82

Prerequisites

  • Python 3.10+
  • MiXCR, TRUST4 for TCR calling
  • immunarch, tcrdist3
  • PyTorch, transformers
  • AlphaFold3 (optional, for structure)

Related Skills

  • TCR_pMHC_Prediction_Agent - Detailed TCR-epitope prediction
  • Neoantigen_Prediction_Agent - Neoantigen identification
  • TME_Immune_Profiling_Agent - Broader immune context
  • TCell_Exhaustion_Analysis_Agent - T cell phenotyping

TCR Sequence Analysis

CDR3 Feature Analysis Meaning
Length Distribution Histogram V(D)J usage
Amino Acid Usage Positional frequency Binding properties
Hydrophobicity CDR3 profile MHC interaction
Charge Net charge Peptide binding
Motif Enrichment k-mer analysis Epitope specificity

Therapeutic TCR Selection Criteria

Criterion Threshold Rationale
Tumor Enrichment >10-fold vs blood Tumor specificity
Clone Size Top 1% in tumor Functional expansion
Neoantigen Binding Predicted positive Target specificity
Safety (Cross-react) No self-peptide hits Safety
HLA Restriction Common alleles Broad applicability

Special Considerations

  1. Sample Quality: Fresh samples preferred for TIL analysis
  2. Sequencing Depth: Sufficient depth for rare clones
  3. Batch Effects: Normalize across sequencing runs
  4. HLA Context: TCR analysis requires HLA typing
  5. Paired Chains: Single-cell for alpha-beta pairing

Cancer-Specific TCR Signatures

Cancer Type Key TCR Features Public TCRs
Melanoma High clonality, MAA-reactive Yes
NSCLC Moderate diversity Limited
CRC-MSI Neoantigen-reactive Variable
HPV+ HNSCC HPV-E6/E7 reactive Yes

Author

AI Group - Biomedical AI Platform

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