Reactome Analysis & Content Service

Prerequisites

uv
: Read the
```
uv
```
skill and follow its Setup instructions to ensure
```
uv
```
is installed and on PATH.
User Notification: If LICENSE_NOTIFICATION.txt does not already exist in this skill 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
Retrieving reaction participants (inputs, outputs, catalysts, regulators)
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

bash

uv run scripts/reactome_analysis.py <command> [options] --output /tmp/out.json

To list all available subcommands and flags, run:

bash

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

bash

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

bash

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:

bash

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

Common options:

--page-size

(alias

--limit

--page

(alias

--offset

--sort-by

--order

--resource

--species

--fdr

--pvalue

4. Token-Based Result Retrieval

bash

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

bash

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

bash

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):

bash

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:

bash

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:

bash

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:

bash

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:

bash

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

bash

uv run scripts/reactome_analysis.py search --query "TP53 apoptosis" --output /tmp/results.json

13. Query Entry by ID

bash

uv run scripts/reactome_analysis.py query --id R-HSA-69278 --output /tmp/entry.json

14. Report & Species Comparison

bash

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

Reference

For detailed API endpoint documentation, see references/api_reference.md.

reactome-database

NPX Install

Tags

SKILL.md Content

Reactome Analysis & Content Service

Prerequisites

Overview

When to Use This Skill

Common Species IDs

Common Pathway IDs

Core Rules

Tool Execution

Feature Domains

1. Database Info

2. Single Identifier Analysis

3. Batch Analysis (Enrichment)

4. Token-Based Result Retrieval

5. Download Results

6. Identifier Mapping

7. Reaction Participants & Mechanism of Action

8. Complex & Set Membership

9. Pathway Hierarchy Navigation

10. Diagram Export

11. Cross-Reference Mapping

12. Search

13. Query Entry by ID

14. Report & Species Comparison

Recipe: Interpreting Gene Set Enrichment

Reference