reactome-database

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SKILL.md (first lines)

# Reactome Database

## Overview

Reactome is a free, open-source, curated pathway database with 2,825+ human pathways. Query biological pathways, perform overrepresentation and expression analysis, map genes to pathways, explore molecular interactions via REST API and Python client for systems biology research.

## When to Use This Skill

This skill should be used when:
- Performing pathway enrichment analysis on gene or protein lists
- Analyzing gene expression data to identify relevant biological pathways
- Querying specific pathway information, reactions, or molecular interactions
- Mapping genes or proteins to biological pathways and processes
- Exploring disease-related pathways and mechanisms
- Visualizing analysis results in the Reactome Pathway Browser
- Conducting comparative pathway analysis across species

## Core Capabilities

Reactome provides two main API services and a Python client library:

### 1. Content Service - Data Retrieval

Query and retrieve biological pathway data, molecular interactions, and entity information.

**Common operations:**
- Retrieve pathway information and hierarchies
- Query specific entities (proteins, reactions, complexes)
- Get participating molecules in pathways
- Access database version and metadata
- Explore pathway compartments and locations

**API Base URL:** `https://reactome.org/ContentService`

### 2. Analysis Service - Pathway Analysis

Perform computational analysis on gene lists and expression data.

**Analysis types:**
- **Overrepresentation Analysis**: Identify statistically significant pathways from gene/protein lists
- **Expression Data Analysis**: Analyze gene expression datasets to find relevant pathways
- **Species Comparison**: Compare pathway data across different organisms

**API Base URL:** `https://reactome.org/AnalysisService`

### 3. reactome2py Python Package

Python client library that wraps Reactome API calls for easier programmatic access.

**Installation:**
```bash
uv pip install reactome2py
```

**Note:** The reactome2py package (version 3.0.0, released January 2021) is functional but not actively maintained. For the most up-to-date functionality, consider using direct REST API calls.

## Querying Pathway Data

### Using Content Service REST API

The Content Service uses REST protocol and returns data in JSON or plain text formats.

**Get database version:**
```python
import requests

response = requests.get("https://reactome.org/ContentService/data/database/version")
version = response.text
print(f"Reactome version: {version}")
```

**Query a specific entity:**
```python
import requests

entity_id = "R-HSA-69278"  # Example pathway ID
response = requests.get(f"https://reactome.org/ContentService/data/query/{entity_id}")
data = response.json()
```

**Get participating molecules in a pathway:**
```python
import requests

event_id = "R-HSA-69278"
response = requests.get(
    f"https://reactome.org/ContentService/data/event/{event_id}/participatingPhysicalEntities"
)
molecules = response.json()
```

### Using reactome2py Package

```python
import reactome2py
from reactome2py import content

# Query pathway information
pathway_info = content.query_by_id("R-HSA-69278")

# Get database version
version = content.get_database_version()
```

**For detailed API endpoints and parameters**, refer to `references/api_reference.md` in this skill.

## Performing Pathway Analysis

### Overrepresentation Analysis

Submit a list of gene/protein identifiers to find enriched pathways.

**Using REST API:**
```python
import requests

# Prepare identifier list
identifiers = ["TP53", "BRCA1", "EGFR", "MYC"]
data = "\n".join(identifiers)

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