---name: simo-multiomics-integration-agent
description: AI-powered spatial integration of multi-omics datasets using probabilistic alignment for comprehensive tissue atlas construction and cellular state mapping.
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:
- simo-multiomics-integration-agent
- automation
- biomedical
measurable_outcome: execute task with >95% success rate.
---"
SIMO Multiomics Integration Agent
The SIMO Multiomics Integration Agent performs spatial integration of multi-omics datasets through probabilistic alignment. Unlike previous tools limited to transcriptomics, SIMO integrates spatial transcriptomics with single-cell RNA-seq and expands to chromatin accessibility, DNA methylation, and proteomics data.
When to Use This Skill
- When integrating spatial transcriptomics with single-cell multi-omics data.
- For constructing comprehensive tissue atlases with spatial context.
- To map epigenomic states (ATAC-seq, methylation) onto spatial coordinates.
- When analyzing multi-modal cellular phenotypes in tissue architecture.
- For spatial deconvolution combining multiple modalities.
Core Capabilities
Spatial-scRNA Integration: Probabilistically align single-cell RNA-seq to spatial coordinates.
Chromatin Accessibility Mapping: Project scATAC-seq profiles onto spatial tissue locations.
DNA Methylation Spatial Mapping: Integrate single-cell methylation data with spatial context.
Multi-Modal Fusion: Combine transcriptomic, epigenomic, and proteomic layers.
Probabilistic Cell-Type Assignment: Assign cell types to spatial spots with uncertainty quantification.
Spatial Niche Identification: Discover cellular niches defined by multi-omic signatures.
Supported Modalities
| Modality |
Input Format |
Spatial Reference |
| scRNA-seq |
AnnData, Seurat |
Visium, MERFISH, Xenium |
| scATAC-seq |
SnapATAC2, ArchR |
Visium, Slide-seq |
| scMethyl |
Bismark, allcools |
Any spatial modality |
| CITE-seq (protein) |
AnnData |
Spatial proteomics |
| Multi-ome (RNA+ATAC) |
Muon, SnapATAC2 |
All platforms |
Integration Algorithm
| Step |
Method |
Purpose |
| Feature Selection |
HVG + marker genes |
Reduce dimensionality |
| Embedding |
Variational autoencoder |
Shared latent space |
| Alignment |
Optimal transport |
Probabilistic matching |
| Spatial Mapping |
Gaussian processes |
Smooth spatial predictions |
| Uncertainty |
Posterior sampling |
Confidence intervals |
Workflow
Input: Spatial transcriptomics (Visium/MERFISH/Xenium), reference single-cell multi-omics.
Preprocessing: Normalize, select features, QC both datasets.
Embedding: Learn joint latent representation across modalities.
Probabilistic Alignment: Compute cell-to-spot assignment probabilities.
Spatial Imputation: Transfer modalities to spatial coordinates.
Niche Analysis: Identify spatial domains by multi-omic signatures.
Output: Integrated spatial multi-omics object, niche assignments, visualizations.
Example Usage
User: "Integrate our scRNA-seq and scATAC-seq data with the spatial transcriptomics to understand chromatin states in different tissue regions."
Agent Action:
python3 Skills/Genomics/SIMO_Multiomics_Integration_Agent/simo_integration.py \
--spatial_data visium_data.h5ad \
--scrna_ref scrna_atlas.h5ad \
--scatac_ref scatac_atlas.h5ad \
--modalities rna,atac \
--n_spots_per_cell 5 \
--uncertainty_quantification true \
--output integrated_spatial_multiome.h5ad
Output Components
| Output |
Description |
Format |
| Integrated Object |
Multi-modal spatial data |
AnnData/Muon |
| Cell Type Map |
Spatial cell type assignments |
GeoTIFF, CSV |
| Chromatin Accessibility Map |
Spatial ATAC patterns |
BigWig, CSV |
| Niche Assignments |
Spatial domain labels |
CSV, Zarr |
| Uncertainty Maps |
Per-spot confidence |
GeoTIFF |
| Gene Activity Scores |
ATAC-derived gene activity |
AnnData layer |
Spatial Platforms Supported
| Platform |
Resolution |
Spots/Cells |
Genes |
| 10x Visium |
55 μm |
~5,000 |
Whole transcriptome |
| 10x Visium HD |
8 μm |
~300,000 |
Whole transcriptome |
| 10x Xenium |
Subcellular |
>100,000 |
300-5,000 panel |
| MERFISH |
Subcellular |
>1M |
100-10,000 panel |
| Slide-seq |
10 μm |
~60,000 |
Whole transcriptome |
| CosMx |
Subcellular |
>1M |
1,000-6,000 panel |
AI/ML Components
Variational Integration:
- Multi-modal VAE for joint embeddings
- Contrastive learning for modality alignment
- Batch correction across datasets
Probabilistic Mapping:
- Optimal transport with entropic regularization
- Gaussian process spatial smoothing
- Bayesian uncertainty estimation
Niche Discovery:
- Multi-view clustering
- Spatial autocorrelation (Moran's I)
- Graph neural networks for niche boundaries
Prerequisites
- Python 3.10+
- Scanpy, Squidpy, Muon
- scvi-tools, SnapATAC2
- POT (Python Optimal Transport)
- PyTorch, GPyTorch
Related Skills
- scGPT_Agent - For foundation model embeddings
- Spatial_Epigenomics_Agent - For spatial epigenomics analysis
- Cell_Cell_Communication - For ligand-receptor analysis
- Nicheformer_Spatial_Agent - For spatial niche modeling
Special Considerations
- Batch Effects: Pre-align datasets from different protocols
- Spot Deconvolution: Lower resolution platforms need deconvolution
- Sparsity: scATAC data requires aggregation strategies
- Compute: Multi-modal integration is memory-intensive
- Validation: Verify spatial patterns with known marker distributions
Applications
| Application |
Use Case |
| Tumor Microenvironment |
Map chromatin states of immune infiltrates |
| Development |
Track lineage chromatin dynamics spatially |
| Neurodegeneration |
Spatial mapping of epigenetic changes |
| Fibrosis |
Understand spatial activation programs |
Author
AI Group - Biomedical AI Platform
1---2name: simo-multiomics-integration-agent3description: ---name: simo-multiomics-integration-agent4---5
6---name: simo-multiomics-integration-agent
7description: AI-powered spatial integration of multi-omics datasets using probabilistic alignment for comprehensive tissue atlas construction and cellular state mapping.
8license: MIT
9metadata:
10 author: AI Group
11 version: "1.0.0"
12 created: "2026-01-20"
13compatibility:
14 - system: Python 3.10+
15allowed-tools:
16 - run_shell_command
17 - read_file
18 - write_file
19
20keywords:
21 - simo-multiomics-integration-agent
22 - automation
23 - biomedical
24measurable_outcome: execute task with >95% success rate.
25---"
26
27# SIMO Multiomics Integration Agent
28
29The **SIMO Multiomics Integration Agent** performs spatial integration of multi-omics datasets through probabilistic alignment. Unlike previous tools limited to transcriptomics, SIMO integrates spatial transcriptomics with single-cell RNA-seq and expands to chromatin accessibility, DNA methylation, and proteomics data.
30
31## When to Use This Skill
32
33* When integrating spatial transcriptomics with single-cell multi-omics data.
34* For constructing comprehensive tissue atlases with spatial context.
35* To map epigenomic states (ATAC-seq, methylation) onto spatial coordinates.
36* When analyzing multi-modal cellular phenotypes in tissue architecture.
37* For spatial deconvolution combining multiple modalities.
38
39## Core Capabilities
40
411. **Spatial-scRNA Integration**: Probabilistically align single-cell RNA-seq to spatial coordinates.
42
432. **Chromatin Accessibility Mapping**: Project scATAC-seq profiles onto spatial tissue locations.
44
453. **DNA Methylation Spatial Mapping**: Integrate single-cell methylation data with spatial context.
46
474. **Multi-Modal Fusion**: Combine transcriptomic, epigenomic, and proteomic layers.
48
495. **Probabilistic Cell-Type Assignment**: Assign cell types to spatial spots with uncertainty quantification.
50
516. **Spatial Niche Identification**: Discover cellular niches defined by multi-omic signatures.
52
53## Supported Modalities
54
55| Modality | Input Format | Spatial Reference |
56|----------|--------------|-------------------|
57| scRNA-seq | AnnData, Seurat | Visium, MERFISH, Xenium |
58| scATAC-seq | SnapATAC2, ArchR | Visium, Slide-seq |
59| scMethyl | Bismark, allcools | Any spatial modality |
60| CITE-seq (protein) | AnnData | Spatial proteomics |
61| Multi-ome (RNA+ATAC) | Muon, SnapATAC2 | All platforms |
62
63## Integration Algorithm
64
65| Step | Method | Purpose |
66|------|--------|---------|
67| Feature Selection | HVG + marker genes | Reduce dimensionality |
68| Embedding | Variational autoencoder | Shared latent space |
69| Alignment | Optimal transport | Probabilistic matching |
70| Spatial Mapping | Gaussian processes | Smooth spatial predictions |
71| Uncertainty | Posterior sampling | Confidence intervals |
72
73## Workflow
74
751. **Input**: Spatial transcriptomics (Visium/MERFISH/Xenium), reference single-cell multi-omics.
76
772. **Preprocessing**: Normalize, select features, QC both datasets.
78
793. **Embedding**: Learn joint latent representation across modalities.
80
814. **Probabilistic Alignment**: Compute cell-to-spot assignment probabilities.
82
835. **Spatial Imputation**: Transfer modalities to spatial coordinates.
84
856. **Niche Analysis**: Identify spatial domains by multi-omic signatures.
86
877. **Output**: Integrated spatial multi-omics object, niche assignments, visualizations.
88
89## Example Usage
90
91**User**: "Integrate our scRNA-seq and scATAC-seq data with the spatial transcriptomics to understand chromatin states in different tissue regions."
92
93**Agent Action**:
94```bash
95python3 Skills/Genomics/SIMO_Multiomics_Integration_Agent/simo_integration.py \
96 --spatial_data visium_data.h5ad \
97 --scrna_ref scrna_atlas.h5ad \
98 --scatac_ref scatac_atlas.h5ad \
99 --modalities rna,atac \
100 --n_spots_per_cell 5 \
101 --uncertainty_quantification true \
102 --output integrated_spatial_multiome.h5ad
103```
104
105## Output Components
106
107| Output | Description | Format |
108|--------|-------------|--------|
109| Integrated Object | Multi-modal spatial data | AnnData/Muon |
110| Cell Type Map | Spatial cell type assignments | GeoTIFF, CSV |
111| Chromatin Accessibility Map | Spatial ATAC patterns | BigWig, CSV |
112| Niche Assignments | Spatial domain labels | CSV, Zarr |
113| Uncertainty Maps | Per-spot confidence | GeoTIFF |
114| Gene Activity Scores | ATAC-derived gene activity | AnnData layer |
115
116## Spatial Platforms Supported
117
118| Platform | Resolution | Spots/Cells | Genes |
119|----------|------------|-------------|-------|
120| 10x Visium | 55 μm | ~5,000 | Whole transcriptome |
121| 10x Visium HD | 8 μm | ~300,000 | Whole transcriptome |
122| 10x Xenium | Subcellular | >100,000 | 300-5,000 panel |
123| MERFISH | Subcellular | >1M | 100-10,000 panel |
124| Slide-seq | 10 μm | ~60,000 | Whole transcriptome |
125| CosMx | Subcellular | >1M | 1,000-6,000 panel |
126
127## AI/ML Components
128
129**Variational Integration**:
130- Multi-modal VAE for joint embeddings
131- Contrastive learning for modality alignment
132- Batch correction across datasets
133
134**Probabilistic Mapping**:
135- Optimal transport with entropic regularization
136- Gaussian process spatial smoothing
137- Bayesian uncertainty estimation
138
139**Niche Discovery**:
140- Multi-view clustering
141- Spatial autocorrelation (Moran's I)
142- Graph neural networks for niche boundaries
143
144## Prerequisites
145
146* Python 3.10+
147* Scanpy, Squidpy, Muon
148* scvi-tools, SnapATAC2
149* POT (Python Optimal Transport)
150* PyTorch, GPyTorch
151
152## Related Skills
153
154* scGPT_Agent - For foundation model embeddings
155* Spatial_Epigenomics_Agent - For spatial epigenomics analysis
156* Cell_Cell_Communication - For ligand-receptor analysis
157* Nicheformer_Spatial_Agent - For spatial niche modeling
158
159## Special Considerations
160
1611. **Batch Effects**: Pre-align datasets from different protocols
1622. **Spot Deconvolution**: Lower resolution platforms need deconvolution
1633. **Sparsity**: scATAC data requires aggregation strategies
1644. **Compute**: Multi-modal integration is memory-intensive
1655. **Validation**: Verify spatial patterns with known marker distributions
166
167## Applications
168
169| Application | Use Case |
170|-------------|----------|
171| Tumor Microenvironment | Map chromatin states of immune infiltrates |
172| Development | Track lineage chromatin dynamics spatially |
173| Neurodegeneration | Spatial mapping of epigenetic changes |
174| Fibrosis | Understand spatial activation programs |
175
176## Author
177
178AI Group - Biomedical AI Platform