
tooluniverse-multi-omics-integration
Multi-omics integration — orchestrate per-layer analysis (transcriptomics, proteomics, epigenomics, genomics, metabolomics) then perform cross-omics correlation, multi-omics clustering, and pathway-level integration. Use for integrative systems-biology analysis, multi-modal disease characterization, and cross-omics biomarker discovery.
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Install
Works with every agent the skills CLI supports.
npx skills add https://github.com/mims-harvard/tooluniverse --skill tooluniverse-multi-omics-integration- 01
Install
Run the command in your project. The CLI asks which agents to install for.
- 02
Describe the task
Ask your agent for something this skill covers. It loads tooluniverse-multi-omics-integration automatically when relevant.
- 03
Review the result
The agent follows the SKILL.md steps, scripts and references bundled with the skill.
SKILL.md
The instructions your agent reads when the skill is triggered.
Multi-Omics Integration
Coordinate and integrate multiple omics datasets for comprehensive systems biology analysis. Orchestrates specialized ToolUniverse skills to perform cross-omics correlation, multi-omics clustering, pathway-level integration, and unified interpretation.
Domain Reasoning
Multi-omics integration asks whether different molecular layers tell a concordant story. If a gene is upregulated in RNA-seq AND its protein is elevated in proteomics, that is concordant evidence of true biological change. Discordance — high mRNA but low protein, or elevated protein without matching mRNA — may indicate post-transcriptional regulation (miRNA silencing, protein degradation, translational control) and is itself a meaningful finding worth reporting. Not every discordance is noise; some are the most interesting biology.
LOOK UP DON'T GUESS
- Expected RNA-protein correlation ranges: compute Spearman r from the actual data; the typical range (0.4-0.6) is a guide, not a guarantee.
- Pathway enrichment results: run
ReactomeAnalysis_pathway_enrichmentor gseapy on the actual gene lists; never list enriched pathways from memory. - eQTL associations: query GTEx or eQTL databases for the specific variant and tissue; do not assume regulatory relationships.
- Methylation-expression directionality at specific loci: retrieve experimental data; promoter repression is the canonical model but exceptions exist.
When to Use This Skill
- User has multiple omics datasets (RNA-seq + proteomics, methylation + expression, etc.)
- Cross-omics correlation queries (e.g., "How does methylation affect expression?")
- Multi-omics biomarker discovery or patient subtyping
- Systems biology questions requiring multiple molecular layers
- Precision medicine applications with multi-omics patient data
Workflow Overview
Phase 1: Data Loading & QC
Load each omics type, format-specific QC, normalize
Supported: RNA-seq, proteomics, methylation, CNV/SNV, metabolomics
Phase 2: Sample Matching
Harmonize sample IDs, find common samples, handle missing omics
Phase 3: Feature Mapping
Map features to common gene-level identifiers
CpG->gene (promoter), CNV->gene, metabolite->enzyme
Phase 4: Cross-Omics Correlation
RNA vs Protein (translation efficiency)
Methylation vs Expression (epigenetic regulation)
CNV vs Expression (dosage effect)
eQTL variants vs Expression (genetic regulation)
Phase 5: Multi-Omics Clustering
MOFA+, NMF, SNF for patient subtyping
Phase 6: Pathway-Level Integration
Aggregate omics evidence at pathway level
Score pathway dysregulation with combined evidence
Phase 7: Biomarker Discovery
Feature selection across omics, multi-omics classification
Phase 8: Integrated Report
Summary, correlations, clusters, pathways, biomarkers
See: phase_details.md for complete code and implementation details.
Supported Data Types
| Omics | Formats | QC Focus |
|---|---|---|
| Transcriptomics | CSV/TSV, HDF5, h5ad | Low-count filter, normalize (TPM/DESeq2), log-transform |
| Proteomics | MaxQuant, Spectronaut, DIA-NN | Missing value imputation, median/quantile normalization |
| Methylation | IDAT, beta matrices | Failed probes, batch correction, cross-reactive filter |
| Genomics | VCF, SEG (CNV) | Variant QC, CNV segmentation |
| Metabolomics | Peak tables | Missing values, normalization |
Core Operations
Sample Matching
def match_samples_across_omics(omics_data_dict):
"""Match samples across multiple omics datasets."""
sample_ids = {k: set(df.columns) for k, df in omics_data_dict.items()}
common_samples = set.intersection(*sample_ids.values())
matched_data = {k: df[sorted(common_samples)] for k, df in omics_data_dict.items()}
return sorted(common_samples), matched_data
Cross-Omics Correlation
from scipy.stats import spearmanr, pearsonr
# RNA vs Protein: expect positive r ~ 0.4-0.6
# Methylation vs Expression: expect negative r (promoter repression)
# CNV vs Expression: expect positive r (dosage effect)
for gene in common_genes:
r, p = spearmanr(rna[gene], protein[gene])
Pathway Integration
# Score pathway dysregulation using combined evidence from all omics
# Aggregate per-gene evidence, then per-pathway
pathway_score = mean(abs(rna_fc) + abs(protein_fc) + abs(meth_diff) + abs(cnv))
See: phase_details.md for full implementations of each operation.
Multi-Omics Clustering Methods
| Method | Description | Best For |
|---|---|---|
| MOFA+ | Latent factors explaining cross-omics variation | Identifying shared/omics-specific drivers |
| Joint NMF | Shared decomposition across omics | Patient subtype discovery |
| SNF | Similarity network fusion | Integrating heterogeneous data types |
ToolUniverse Skills Coordination
| Skill | Used For | Phase |
|---|---|---|
tooluniverse-rnaseq-deseq2 | RNA-seq analysis | 1, 4 |
tooluniverse-epigenomics | Methylation, ChIP-seq | 1, 4 |
tooluniverse-variant-analysis | CNV/SNV processing | 1, 3, 4 |
tooluniverse-protein-interactions | Protein network context | 6 |
tooluniverse-gene-enrichment | Pathway enrichment | 6 |
tooluniverse-expression-data-retrieval | Public data retrieval | 1 |
tooluniverse-target-research | Gene/protein annotation | 3, 8 |
Use Cases
Cancer Multi-Omics
Integrate TCGA RNA-seq + proteomics + methylation + CNV to identify patient subtypes, cross-omics driver genes, and multi-omics biomarkers.
eQTL + Expression + Methylation
Identify SNP -> methylation -> expression regulatory chains (mediation analysis).
Drug Response Multi-Omics
Predict drug response using baseline multi-omics profiles; identify resistance/sensitivity pathways.
See: phase_details.md "Use Cases" for detailed step-by-step workflows.
Quantified Minimums
| Component | Requirement |
|---|---|
| Omics types | At least 2 datasets |
| Common samples | At least 10 across omics |
| Cross-correlation | Pearson/Spearman computed |
| Clustering | At least one method (MOFA+, NMF, or SNF) |
| Pathway integration | Enrichment with multi-omics evidence scores |
| Report | Summary, correlations, clusters, pathways, biomarkers |
Limitations
- Sample size: n >= 20 recommended for integration
- Missing data: Pairwise integration if not all samples have all omics
- Batch effects: Different platforms require careful normalization
- Computational: Large datasets may require significant memory
- Interpretation: Results require domain expertise for validation
References
- MOFA+: https://doi.org/10.1186/s13059-020-02015-1
- Similarity Network Fusion: https://doi.org/10.1038/nmeth.2810
- Multi-omics review: https://doi.org/10.1038/s41576-019-0093-7
- See individual ToolUniverse skill documentation for omics-specific methods
Detailed Reference
- phase_details.md - Complete code for all phases, correlation functions, clustering, pathway integration, biomarker discovery, report template, and detailed use cases
FAQ
What does the tooluniverse-multi-omics-integration skill do?
Multi-omics integration — orchestrate per-layer analysis (transcriptomics, proteomics, epigenomics, genomics, metabolomics) then perform cross-omics correlation, multi-omics clustering, and pathway-level integration. Use for integrative systems-biology analysis, multi-modal disease characterization, and cross-omics biomarker discovery.
How do I install tooluniverse-multi-omics-integration?
Run npx skills add https://github.com/mims-harvard/tooluniverse --skill tooluniverse-multi-omics-integration in your project. The skills CLI detects the agents you use and copies the skill into the right folder. For Claude Code you can also place the skill folder at ~/.claude/skills/tooluniverse-multi-omics-integration/ (personal) or .claude/skills/tooluniverse-multi-omics-integration/ (project).
Which AI agents can use tooluniverse-multi-omics-integration?
Any agent that supports the open Agent Skills format (a folder with a SKILL.md file), including Claude Code, Codex, Cursor, GitHub Copilot, Gemini CLI, Windsurf, Cline, OpenCode and more.
Is tooluniverse-multi-omics-integration safe to install?
No partner security audit is available yet. Skills can run commands and scripts, so read the SKILL.md and any bundled files before installing.
Who maintains tooluniverse-multi-omics-integration?
It is published by mims-harvard in mims-harvard/tooluniverse. It has 399 recorded installs.
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