Tme immune profiling agent
Skill FridrichMethod/awesome-skills/skills/tme-immune-profiling-agent
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Comprehensive AI-powered tumor microenvironment immune profiling integrating bulk deconvolution, single-cell analysis, and spatial transcriptomics for immunotherapy biomarker discovery.
SKILL.md
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TME Immune Profiling Agent
The TME Immune Profiling Agent provides comprehensive tumor microenvironment (TME) immune profiling by integrating multiple data modalities including bulk RNA-seq deconvolution, single-cell transcriptomics, spatial transcriptomics, and multiplex immunofluorescence. It enables biomarker discovery for immunotherapy response and TME-based patient stratification.
When to Use This Skill
- When characterizing immune composition of tumor microenvironment.
- For predicting immunotherapy response from TME profiles.
- To identify immune cell states and functional programs.
- When analyzing spatial organization of immune infiltrates.
- For discovering TME-based biomarkers and therapeutic targets.
Core Capabilities
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Bulk Deconvolution: Estimate immune cell fractions from bulk RNA-seq.
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Single-Cell Immune Profiling: Deep characterization of immune populations.
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Spatial Immune Architecture: Map immune cell locations and neighborhoods.
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Immune Phenotype Classification: Hot/cold/excluded tumor classification.
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Functional State Analysis: Exhaustion, activation, memory signatures.
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Response Prediction: Multi-modal immunotherapy response models.
Immune Cell Types Profiled
| Cell Type | Subtypes | Key Markers |
|---|---|---|
| T cells | CD8+, CD4+, Treg, Th1/2/17 | CD3, CD8, CD4, FOXP3 |
| B cells | Naive, memory, plasma | CD19, CD20, CD138 |
| NK cells | CD56bright, CD56dim | NKG7, NCAM1 |
| Macrophages | M1, M2, TAM | CD68, CD163, CD206 |
| Dendritic | cDC1, cDC2, pDC | CLEC9A, CD1C, BDCA2 |
| MDSC | M-MDSC, PMN-MDSC | CD33, CD11b, ARG1 |
| CAF | myCAF, iCAF, apCAF | FAP, ACTA2, COL1A1 |
Deconvolution Methods
| Method | Algorithm | Cell Types | Best For |
|---|---|---|---|
| CIBERSORTx | SVR | 22 | Gold standard |
| xCell | ssGSEA | 64 | Comprehensive |
| EPIC | Constrained regression | 8 | Tumor/stroma |
| MCP-counter | Marker genes | 10 | Robust scores |
| quanTIseq | Deconvolution | 10 | Pan-cancer |
| TIMER2.0 | Multiple | Variable | Integrated |
Workflow
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Input: Bulk RNA-seq, scRNA-seq, spatial data, or IHC images.
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Deconvolution: Estimate cell fractions from bulk data.
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Single-Cell Analysis: Deep immune phenotyping if available.
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Spatial Mapping: Localize immune populations in tissue.
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Integration: Combine modalities for comprehensive profile.
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Classification: Assign TME phenotype (hot/cold/excluded).
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Output: Immune profiles, visualizations, response predictions.
Example Usage
User: "Profile the tumor microenvironment of this lung cancer cohort to identify immunotherapy responders."
Agent Action:
python3 Skills/Immunology_Vaccines/TME_Immune_Profiling_Agent/tme_profiling.py \
--bulk_rna expression_matrix.tsv \
--scRNA_data scRNA_lung.h5ad \
--spatial_data visium_tumor.h5ad \
--cancer_type nsclc \
--deconvolution_methods cibersortx,epic,mcpcounter \
--response_labels clinical_response.csv \
--output tme_profiles/
TME Phenotypes
| Phenotype | Characteristics | Immunotherapy Response |
|---|---|---|
| Immune Hot | High TIL infiltration, PD-L1+ | Favorable |
| Immune Cold | Low TIL, low inflammation | Poor |
| Immune Excluded | TILs at margin, not penetrating | Intermediate |
| Immune Suppressed | TILs + MDSCs/Tregs | Variable |
Output Components
| Output | Description | Format |
|---|---|---|
| Cell Fractions | Per-sample immune estimates | .csv |
| TME Classification | Hot/cold/excluded labels | .csv |
| Immune Scores | Composite signatures | .csv |
| Spatial Maps | Cell type locations | .h5ad |
| Neighborhood Analysis | Immune niches | .csv |
| Response Prediction | IO probability | .json |
| Visualizations | Deconvolution plots | .png, .pdf |
Immune Signatures
| Signature | Genes | Interpretation |
|---|---|---|
| Cytotoxic | PRF1, GZMB, GNLY | T cell killing |
| Exhaustion | PDCD1, LAG3, HAVCR2, TIGIT | T cell dysfunction |
| IFN-gamma | IFNG, STAT1, IRF1 | Inflammation |
| TLS | CD20, CD4, BCL6 | Tertiary lymphoid |
| Exclusion | TGFB1, FAP, COL1A1 | Stromal barrier |
AI/ML Components
Deconvolution Enhancement:
- Deep learning deconvolution
- Multi-method ensemble
- Single-cell reference optimization
Response Prediction:
- Multi-modal fusion (bulk + spatial)
- Survival analysis integration
- Transfer learning across cancers
Spatial Analysis:
- Graph neural networks for niches
- Attention for region importance
- Cell-cell interaction networks
Clinical Applications
| Application | TME Feature | Clinical Decision |
|---|---|---|
| IO Selection | Immune hot phenotype | Prioritize IO |
| Combination | Cold + excluded | Consider combo |
| Prognosis | TLS presence | Favorable outcome |
| Biomarker | CD8+ density | Response prediction |
| Resistance | MDSC enrichment | Address suppression |
Performance Benchmarks
| Task | Dataset | Performance |
|---|---|---|
| IO Response | NSCLC | AUC 0.78 |
| IO Response | Melanoma | AUC 0.82 |
| TME Classification | Pan-cancer | Accuracy 85% |
| Survival | TCGA | C-index 0.72 |
Prerequisites
- Python 3.10+
- CIBERSORTx, EPIC, xCell
- Scanpy, Squidpy
- PyTorch for deep learning
- R for certain deconvolution methods
Related Skills
- TCR_Repertoire_Analysis_Agent - T cell specificity
- TCell_Exhaustion_Analysis_Agent - Exhaustion phenotyping
- Spatial_Epigenomics_Agent - Spatial analysis
- Nicheformer_Spatial_Agent - Spatial foundation models
Spatial Immune Metrics
| Metric | Definition | Clinical Relevance |
|---|---|---|
| Immune Distance | Distance to tumor edge | Exclusion |
| Clustering Coefficient | Immune aggregation | TLS formation |
| CD8/Treg Ratio | Spatial ratio | Effector balance |
| Contact Score | Immune-tumor contacts | Direct killing |
| Neighborhood Entropy | Mixing vs segregation | TME organization |
Special Considerations
- Reference Panel: Use cancer-type specific references
- Batch Correction: Normalize across samples/platforms
- Purity Effects: Account for tumor purity in deconvolution
- Single-Cell Validation: Validate bulk estimates with scRNA
- Spatial Context: Bulk loses spatial information
Therapeutic Implications
| TME State | Therapeutic Strategy |
|---|---|
| Hot, PD-L1+ | Anti-PD-1/PD-L1 |
| Cold | Oncolytic virus, radiation, chemo |
| Excluded | TGF-beta inhibition, VEGF targeting |
| Suppressed | Treg depletion, MDSC targeting |
| TLS+ | Excellent IO candidate |
Author
AI Group - Biomedical AI Platform
<!-- AUTHOR_SIGNATURE: 9a7f3c2e-MD-BABU-MIA-2026-MSSM-SECURE -->