Query the Reactome database (Analysis and Content Services). Use when the user asks about pathway analysis, gene list enrichment, retrieving results by token, finding unmapped or not-found identifiers, mapping identifiers, reaction participants (inputs, outputs), pathway hierarchy (including top-level pathways), diagram export, cross-reference mapping, or searching the knowledgebase.
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uv: Read the uv skill and follow its Setup instructions to ensure uv is installed and on PATH.
User Notification: If .licenses/reactome_database_LICENSE.txt does not already exist in the workspace root directory then (1) prominently notify the user to check the terms at https://reactome.org/license and https://reactome.org/cite, then (2) create the file recording the notification text and timestamp.
Overview
Reactome is a free, open-source, curated pathway database. This skill wraps both the Analysis Service (https://reactome.org/AnalysisService/) and the Content Service (https://reactome.org/ContentService/) providing pathway enrichment analysis, identifier mapping, reaction details, pathway hierarchy navigation, diagram export, cross-reference mapping, and search.
When to Use This Skill
Performing pathway enrichment (overrepresentation) analysis on gene/protein lists
Retrieving analysis results using a token from previous enrichment
Identifying which genes or proteins were not found in a pathway analysis
Analyzing gene expression data against pathway annotations
Mapping identifiers to Reactome entities across species
Navigating pathway hierarchy and listing top-level pathways
Finding which complexes or sets contain a protein
Exporting pathway/reaction diagrams (PNG/SVG) with gene highlighting
Cross-referencing identifiers across databases (UniProt, Ensembl, etc.)
Searching the Reactome knowledgebase
Downloading analysis reports (PDF, CSV, JSON)
Comparing pathways across species
Common Species IDs
Reference list for common research organisms:
Homo sapiens
ID: 9606
Mus musculus (Mouse)
ID: 48892
Rattus norvegicus (Rat)
ID: 48895
Common Pathway IDs
Reference list for commonly used Reactome pathway stable IDs:
Cell Cycle
Stable ID: R-HSA-1640170
Notes: Top-level pathway (broad)
Cell Cycle, Mitotic
Stable ID: R-HSA-69278
Notes: Specific sub-pathway — use this for diagrams and drill-downs
Immune System
Stable ID: R-HSA-168256
Notes: Top-level pathway
Signal Transduction
Stable ID: R-HSA-162582
Notes: Top-level pathway
Gene Expression
Stable ID: R-HSA-74160
Notes: Top-level pathway
Programmed Cell Death
Stable ID: R-HSA-5357801
Notes: Top-level pathway
Important: When the user asks for a "Cell Cycle" diagram or analysis, prefer the specific Cell Cycle, Mitotic pathway (R-HSA-69278) unless the user explicitly requests the top-level overview. The examples throughout this document use R-HSA-69278.
Core Rules
Always use --output: Every subcommand requires --output <file> to write results to a file. Never rely on stdout for large results.
Default species is Homo sapiens: Use --species to override.
Tokens expire after 7 days: Store tokens from analysis results to retrieve them later without re-submitting data.
Use --fdr and --pvalue to filter: Enrichment results can be overwhelming. Filter with --fdr 0.05 or --pvalue 0.01 to focus on statistically significant pathways.
Identifier formats: Reactome auto-detects identifiers including gene symbols (TP53), UniProt (P04637), Ensembl (ENSG00000141510), ChEBI, OMIM, EntrezGene, and many more.
Handle large outputs: For commands that return large data (like species-comparison), use the --summary flag to truncate lists and avoid exceeding workspace file size limits (1MB).
Notification: If this skill is used, ensure this is mentioned in the output.
Tool Execution
The CLI tool is at scripts/reactome_analysis.py. Run with uv:
uv run scripts/reactome_analysis.py <command> [options] --output /tmp/out.json
To list all available subcommands and flags, run:
uv run scripts/reactome_analysis.py --help
Use --help to verify available subcommands or flags before executing an unfamiliar command.
Feature Domains
1. Database Info
uv run scripts/reactome_analysis.py db-version --output /tmp/version.json
uv run scripts/reactome_analysis.py db-name --output /tmp/name.json
2. Single Identifier Analysis
uv run scripts/reactome_analysis.py identifier --id TP53 --output /tmp/tp53.json
uv run scripts/reactome_analysis.py identifier-projection --id TP53 --output /tmp/tp53_proj.json
3. Batch Analysis (Enrichment)
Submit a list of identifiers for overrepresentation or expression analysis:
uv run scripts/reactome_analysis.py analyze --data "TP53,BRCA1,EGFR" --output /tmp/enrich.json
uv run scripts/reactome_analysis.py analyze --file genes.txt --output /tmp/enrich.json
uv run scripts/reactome_analysis.py analyze-projection --data "TP53,BRCA1" --output /tmp/proj.json
uv run scripts/reactome_analysis.py analyze --data "TP53,BRCA1" --fdr 0.05 --output /tmp/sig.json
uv run scripts/reactome_analysis.py token-result --token TOKEN --output /tmp/result.json
uv run scripts/reactome_analysis.py token-not-found --token TOKEN --output /tmp/notfound.json
uv run scripts/reactome_analysis.py token-resources --token TOKEN --output /tmp/resources.json
uv run scripts/reactome_analysis.py token-found-entities --token TOKEN --pathway R-HSA-69278 --output /tmp/found.json
uv run scripts/reactome_analysis.py token-filter-species --token TOKEN --species-filter 9606 --output /tmp/filtered.json
uv run scripts/reactome_analysis.py token-reactions-pathway --token TOKEN --pathway R-HSA-69278 --output /tmp/rxns.json
5. Download Results
uv run scripts/reactome_analysis.py download-result --token TOKEN --output /tmp/full.json
uv run scripts/reactome_analysis.py download-pathways --token TOKEN --output /tmp/pathways.csv
uv run scripts/reactome_analysis.py download-found --token TOKEN --output /tmp/found.csv
uv run scripts/reactome_analysis.py download-not-found --token TOKEN --output /tmp/notfound.csv
6. Identifier Mapping
uv run scripts/reactome_analysis.py mapping --data "TP53,BRCA1" --output /tmp/mapped.json
uv run scripts/reactome_analysis.py mapping-projection --data "TP53" --output /tmp/mapped_proj.json
7. Reaction Participants & Mechanism of Action
Retrieve the molecular participants of a reaction (inputs, outputs, catalysts):
uv run scripts/reactome_analysis.py participants --id R-HSA-6804194 --output /tmp/participants.json
uv run scripts/reactome_analysis.py participating-entities --id R-HSA-6804194 --output /tmp/entities.json
8. Complex & Set Membership
Find which complexes or sets contain a given entity:
uv run scripts/reactome_analysis.py component-of --id R-HSA-69488 --output /tmp/complexes.json
9. Pathway Hierarchy Navigation
Move up (ancestors) or down (contained events) the pathway hierarchy:
uv run scripts/reactome_analysis.py event-ancestors --id R-HSA-69278 --output /tmp/ancestors.json
uv run scripts/reactome_analysis.py contained-events --id R-HSA-69278 --output /tmp/steps.json
uv run scripts/reactome_analysis.py top-pathways --output /tmp/top.json
uv run scripts/reactome_analysis.py low-pathways --id R-HSA-69488 --output /tmp/low.json
10. Diagram Export
Export pathway or reaction diagrams as PNG/SVG, with optional gene highlighting:
uv run scripts/reactome_analysis.py diagram --id R-HSA-69278 --output /tmp/diagram.png
uv run scripts/reactome_analysis.py diagram --id R-HSA-69278 --highlight TP53 --output /tmp/highlighted.png
uv run scripts/reactome_analysis.py diagram --id R-HSA-69278 --format svg --output /tmp/diagram.svg
uv run scripts/reactome_analysis.py reaction-diagram --id R-HSA-6804194 --output /tmp/rxn.png
11. Cross-Reference Mapping
Resolve identifiers to Reactome internal IDs and cross-references:
uv run scripts/reactome_analysis.py xref-mapping --id TP53 --output /tmp/xref.json
uv run scripts/reactome_analysis.py xref-mapping-batch --data "TP53,BRCA1" --output /tmp/xrefs.json
12. Search
uv run scripts/reactome_analysis.py search --query "TP53 apoptosis" --output /tmp/results.json
13. Query Entry by ID
uv run scripts/reactome_analysis.py query --id R-HSA-69278 --output /tmp/entry.json
14. Report & Species Comparison
uv run scripts/reactome_analysis.py report --token TOKEN --output /tmp/report.pdf
uv run scripts/reactome_analysis.py species-comparison --species-id 48892 --output /tmp/species.json
# Use --summary to truncate large output and avoid workspace file size limits
uv run scripts/reactome_analysis.py species-comparison --species-id 48892 --summary --output /tmp/species.json
Recipe: Interpreting Gene Set Enrichment
A step-by-step workflow for interpreting gene set enrichment results:
Submit gene list with projection to human pathways: bash uv run scripts/reactome_analysis.py analyze-projection \ --data "TP53,BRCA1,EGFR,MYC,PTEN" --fdr 0.05 --output /tmp/enrichment.json
Inspect top pathways — examine pathwaysFound, top pathway names, p-values, and FDR values in the output.
Drill into a pathway — get its sub-events and reaction details: bash uv run scripts/reactome_analysis.py contained-events --id R-HSA-69278 --output /tmp/steps.json uv run scripts/reactome_analysis.py participants --id <reaction_id> --output /tmp/parts.json
Visualise — export a diagram with your genes highlighted: bash uv run scripts/reactome_analysis.py diagram --id R-HSA-69278 \ --highlight "TP53,BRCA1" --output /tmp/diagram.png
Check hierarchy — navigate up to see broader biological context: bash uv run scripts/reactome_analysis.py event-ancestors --id R-HSA-69278 --output /tmp/ancestors.json
Cross-reference — map identifiers to other databases: bash uv run scripts/reactome_analysis.py xref-mapping --id TP53 --output /tmp/xrefs.json
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