ensembl-database

# Ensembl Database

## Overview

Access and query the Ensembl genome database, a comprehensive resource for vertebrate genomic data maintained by EMBL-EBI. The database provides gene annotations, sequences, variants, regulatory information, and comparative genomics data for over 250 species. Current release is 115 (September 2025).

## When to Use This Skill

This skill should be used when:

- Querying gene information by symbol or Ensembl ID
- Retrieving DNA, transcript, or protein sequences
- Analyzing genetic variants using the Variant Effect Predictor (VEP)
- Finding orthologs and paralogs across species
- Accessing regulatory features and genomic annotations
- Converting coordinates between genome assemblies (e.g., GRCh37 to GRCh38)
- Performing comparative genomics analyses
- Integrating Ensembl data into genomic research pipelines

## Core Capabilities

### 1. Gene Information Retrieval

Query gene data by symbol, Ensembl ID, or external database identifiers.

**Common operations:**
- Look up gene information by symbol (e.g., "BRCA2", "TP53")
- Retrieve transcript and protein information
- Get gene coordinates and chromosomal locations
- Access cross-references to external databases (UniProt, RefSeq, etc.)

**Using the ensembl_rest package:**
```python
from ensembl_rest import EnsemblClient

client = EnsemblClient()

# Look up gene by symbol
gene_data = client.symbol_lookup(
    species='human',
    symbol='BRCA2'
)

# Get detailed gene information
gene_info = client.lookup_id(
    id='ENSG00000139618',  # BRCA2 Ensembl ID
    expand=True
)
```

**Direct REST API (no package):**
```python
import requests

server = "https://rest.ensembl.org"

# Symbol lookup
response = requests.get(
    f"{server}/lookup/symbol/homo_sapiens/BRCA2",
    headers={"Content-Type": "application/json"}
)
gene_data = response.json()
```

### 2. Sequence Retrieval

Fetch genomic, transcript, or protein sequences in various formats (JSON, FASTA, plain text).

**Operations:**
- Get DNA sequences for genes or genomic regions
- Retrieve transcript sequences (cDNA)
- Access protein sequences
- Extract sequences with flanking regions or modifications

**Example:**
```python
# Using ensembl_rest package
sequence = client.sequence_id(
    id='ENSG00000139618',  # Gene ID
    content_type='application/json'
)

# Get sequence for a genomic region
region_seq = client.sequence_region(
    species='human',
    region='7:140424943-140624564'  # chromosome:start-end
)
```

### 3. Variant Analysis

Query genetic variation data and predict variant consequences using the Variant Effect Predictor (VEP).

**Capabilities:**
- Look up variants by rsID or genomic coordinates
- Predict functional consequences of variants
- Access population frequency data
- Retrieve phenotype associations

**VEP example:**
```python
# Predict variant consequences
vep_result = client.vep_hgvs(
    species='human',
    hgvs_notation='ENST00000380152.7:c.803C>T'
)

# Query variant by rsID
variant = client.variation_id(
    species='human',
    id='rs699'
)
```

### 4. Comparative Genomics

Perform cross-species comparisons to identify orthologs, paralogs, and evolutionary relationships.

**Operations:**
- Find orthologs (same gene in different species)
- Identify paralogs (related genes in same species)
- Access gene trees showing evolutionary relationships
- Retrieve gene family information

**Example:**
```python
# Find orthologs for a human gene
orthologs = client.homology_ensemblgene(
    id='ENSG00000139618',  # Human BRCA2
    target_species='mouse'
)

# Get gene tree
gene_tree = client.genetree_member_symbol(
    species='human',
    symbol='BRCA2'
)
```

### 5. Genomic Region Analysis

Find all genomic features (genes, transcripts, regulatory elements) in a specific region.

**Use cases:**
- Identify all genes in a chromosomal region
- Find regulatory features (promoters, enhancers)
- Locate variants within a region
- Retrieve structural features

**Example:**
```python
# Find all features in a region
features = client.overlap_region(
    species='human',
    region='7:140424943-140624564',
    feature='gene'
)
```

### 6. Assembly Mapping

Convert coordinates between different genome assemblies (e.g., GRCh37 to GRCh38).

**Important:** Use `https://grch37.rest.ensembl.org` for GRCh37/hg19 queries and `https://rest.ensembl.org` for current assemblies.

**Example:**
```python
from ensembl_rest import AssemblyMapper

# Map coordinates from GRCh37 to GRCh38
mapper = AssemblyMapper(
    species='human',
    asm_from='GRCh37',
    asm_to='GRCh38'
)

mapped = mapper.map(chrom='7', start=140453136, end=140453136)
```

## API Best Practices

### Rate Limiting

The Ensembl REST API has rate limits. Follow these practices:

1. **Respect rate limits:** Maximum 15 requests per second for anonymous users
2. **Handle 429 responses:** When rate-limited, check the `Retry-After` header and wait
3. **Use batch endpoints:** When querying multiple items, use batch endpoints where available
4. **Cache results:** Store frequently accessed data to reduce API calls

### Error Handling

Always implement proper error handling:

```python
import requests
import time

def query_ensembl(endpoint, params=None, max_retries=3):
    server = "https://rest.ensembl.org"
    headers = {"Content-Type": "application/json"}

    for attempt in range(max_retries):
        response = requests.get(
            f"{server}{endpoint}",
            headers=headers,
            params=params
        )

        if response.status_code == 200:
            return response.json()
        elif response.status_code == 429:
            # Rate limited - wait and retry
            retry_after = int(response.headers.get('Retry-After', 1))
            time.sleep(retry_after)
        else:
            response.raise_for_status()

    raise Exception(f"Failed after {max_retries} attempts")
```

## Installation

### Python Package (Recommended)

```bash
uv pip install ensembl_rest
```

The `ensembl_r