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name: 'nicheformer-spatial-agent' description: 'Foundation model-powered spatial transcriptomics analysis leveraging 53M+ spatially resolved cells for cellular architecture modeling and tissue niche discovery.' measurable_outcome: Execute skill workflow successfully with valid output within 15 minutes. allowed-tools:

• read_file
• run_shell_command

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Nicheformer Spatial Agent

The Nicheformer Spatial Agent leverages the Nicheformer foundation model, trained on over 53 million spatially resolved cells, to model cellular architecture and tissue microenvironments with unprecedented accuracy. It enables spatial context-aware cell type annotation, niche discovery, and tissue organization analysis.

When to Use This Skill

• When analyzing spatial transcriptomics requiring deep cellular context understanding.
• For identifying tissue niches and cellular neighborhoods.
• To predict cell-cell interactions based on spatial proximity.
• When transferring annotations from atlases to new spatial data.
• For studying tissue architecture and organization patterns.

Core Capabilities

1. Spatial Context Embeddings: Generate embeddings that capture both gene expression and spatial context.

2. Niche Discovery: Identify recurrent cellular neighborhoods across tissues.

3. Zero-Shot Cell Type Annotation: Transfer cell type labels without retraining.

4. Spatial Perturbation Prediction: Predict effects of removing cell types from niches.

5. Cross-Tissue Transfer: Apply models trained on one tissue to another.

6. Tissue Architecture Analysis: Quantify spatial organization patterns.

Model Architecture

Component	Description	Parameters
Expression Encoder	Gene expression transformer	~100M
Spatial Encoder	Neighborhood graph attention	~50M
Fusion Layer	Cross-attention expression + spatial	~30M
Pretraining Data	53M+ spatially resolved cells	Multi-tissue

Supported Spatial Technologies

Platform	Coverage	Resolution
10x Xenium	Full support	Subcellular
MERFISH	Full support	Subcellular
CosMx	Full support	Subcellular
Visium	Supported	55 μm spot
Slide-seq	Supported	10 μm bead
seqFISH+	Supported	Subcellular
STARmap	Supported	Subcellular

Workflow

1. Input: Spatial transcriptomics data with coordinates.

2. Preprocessing: Normalize, filter, construct spatial graphs.

3. Embedding Generation: Compute Nicheformer embeddings per cell/spot.

4. Niche Clustering: Identify spatial domains and niches.

5. Annotation Transfer: Map cell types from reference atlases.

6. Interaction Analysis: Predict cell-cell communication in niches.

7. Output: Annotated spatial data, niche assignments, interaction networks.

Example Usage

User: "Use Nicheformer to identify cellular niches in this tumor spatial transcriptomics dataset."

Agent Action:

python3 Skills/Genomics/Nicheformer_Spatial_Agent/nicheformer_analysis.py \
    --spatial_data xenium_tumor.h5ad \
    --model_weights nicheformer_pretrained.pt \
    --k_neighbors 15 \
    --niche_resolution 0.5 \
    --reference_atlas tabula_sapiens.h5ad \
    --output tumor_niches_analysis/

Niche Analysis Outputs

Output	Description	Format
Cell Embeddings	Spatial-aware embeddings	.h5ad obsm
Niche Labels	Cluster assignments	.csv
Niche Signatures	Defining gene programs	.csv
Spatial Maps	Visualizations	.png, .pdf
Interaction Network	Cell-cell edges	.graphml
Architecture Metrics	Tissue organization scores	.json

Niche Types Detected

Niche Category	Examples	Markers
Immune Aggregates	TLS, germinal centers	CD20, CD3, PD1
Tumor Core	Hypoxic, proliferative	HIF1A, MKI67
Invasion Front	EMT, matrix remodeling	VIM, MMP9
Stromal	Fibroblast niches	COL1A1, ACTA2
Vascular	Perivascular zones	PECAM1, VWF
Neural	Nerve-associated	NCAM1, NGF

AI/ML Components

Foundation Model:

• Transformer backbone with spatial attention
• Pretrained on 53M cells across tissues
• Self-supervised contrastive learning

Spatial Graph Construction:

• Delaunay triangulation
• k-NN with distance threshold
• Hierarchical multi-scale graphs

Transfer Learning:

• Zero-shot annotation via embedding similarity
• Few-shot fine-tuning for novel cell types
• Domain adaptation for new tissues

Performance Benchmarks

Task	Metric	Performance
Cell Type Annotation	Accuracy	92-96%
Niche Recovery	ARI	0.85-0.92
Cross-Tissue Transfer	F1	0.88-0.94
Batch Integration	kBET	0.90+

Prerequisites

• Python 3.10+
• PyTorch 2.0+, PyTorch Geometric
• Scanpy, Squidpy
• Nicheformer pretrained weights
• GPU with 16GB+ VRAM recommended

Related Skills

• SIMO_Multiomics_Integration_Agent - For multi-omics spatial integration
• scGPT_Agent - For single-cell foundation models
• Cell_Cell_Communication - For ligand-receptor analysis
• Spatial_Epigenomics_Agent - For spatial epigenomics

Spatial Architecture Metrics

Metric	Description	Interpretation
Moran's I	Spatial autocorrelation	Clustering degree
Ripley's K	Point pattern analysis	Aggregation vs dispersion
Neighborhood Enrichment	Cell type co-occurrence	Preferential associations
Connectivity	Graph topology	Tissue organization

Special Considerations

1. Gene Panel Overlap: Ensure sufficient overlap with training data genes
2. Tissue Context: Model performance varies by tissue type
3. Resolution Effects: Aggregate for spot-based technologies
4. GPU Memory: Batch processing for large datasets
5. Validation: Compare with known tissue architecture

Applications

Domain	Application
Oncology	Tumor microenvironment niches
Immunology	Tertiary lymphoid structures
Development	Organ patterning and morphogenesis
Neuroscience	Brain region architecture
Pathology	Disease-specific spatial signatures

Author

AI Group - Biomedical AI Platform

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