ensembl-database

Este extracto es una copia guardada durante la revisión. La fuente externa contiene la versión completa y actual.

---
name: ensembl-database
description: >
  Query the Ensembl database to resolve gene, transcript, and protein IDs,
  fetch genomic or protein sequences, retrieve gene structures (exons), and
  get variant consequence and effect predictions (VEP). Use this skill as a
  primary ID translator, genomic sequence database and variant effect prediction
  tool.
---

# Ensembl Database: ID Mapping and Genomic Features

## Prerequisites

1.  **`uv`**: Read the `uv` skill and follow its Setup instructions to ensure
    `uv` is installed and on PATH.
2.  **User Notification**: If .licenses/ensembl_database_LICENSE.txt does not
    already exist in the workspace root directory then (1) prominently notify
    the user to check the terms at https://useast.ensembl.org/index.html and
    https://github.com/Ensembl/ensembl-rest/wiki, then (2) create the file
    recording the notification text and timestamp.

## Overview

The Ensembl database is a resource for genome annotation. This skill allows you
to interact with the Ensembl REST API to resolve ambiguous symbols,
cross-reference IDs (RefSeq, HGNC, UniProt, ENSG), fetch raw sequences, and
retrieve detailed transcript structures.

**Key Concepts:**

-   **ENSG (Gene):** Stable identifier for a human gene. Other species will have
    different three-letter species codes.
-   **ENST (Transcript):** Stable identifier for a transcript (splicing
    isoform).
-   **ENSP (Protein):** Stable identifier for a translated protein.
-   **MANE Select:** The consensus primary transcript agreed upon by Ensembl and
    NCBI.
-   **Canonical:** Ensembl's representative transcript (used if MANE is not
    available or non-human).

## Core Rules

-   **Use the Wrapper**: ALWAYS execute the provided helper scripts to query the
    database rather than accessing the database directly. The scripts
    automatically enforce the required rate limit gracefully.
-   **Default Species:** If the species is absent or ambiguous in the prompt,
    default to `"human"`. You MUST explicitly flag this default to the user to
    ensure they are aware.
-   **Primary Transcripts:** When listing transcripts for a gene, only return
    the MANE Select transcript (for human) or the Canonical transcript (for
    others) unless the user explicitly asks for all alternative isoforms. You
    MUST flag to the user when multiple transcripts are available and you are
    defaulting to the primary one.
-   **Assembly Handling:** The default assembly is GRCh38. For GRCh37 requests,
    you MUST use the `--assembly GRCh37` flag. You MUST explicitly flag to the
    user when a non-default assembly is being used.
-   **Output Location:** The script writes full JSON/FASTA output to temporary
    files in `/tmp` by default, or to a user-specified file using the `--output`
    flag. It also prints a concise summary to stdout.
-   **Notification**: If this skill is used, ensure this is mentioned in the
    output.

### Available Commands

**1. Resolve Gene ID** — Resolve a symbol, alias, or RefSeq ID to ENSG ID(s).
Automatically falls back to resolving synonyms if primary symbol is not found.

```bash
uv run scripts/ensembl_api.py resolve-gene TP53 --species human --output tp53.json
uv run scripts/ensembl_api.py resolve-gene PCL2 --output pcl2.json # Falls back to synonym resolution
```

**2. Map ID to External Database** — Cross-reference an Ensembl ID to UniProt,
HGNC, RefSeq, etc.

```bash
uv run scripts/ensembl_api.py map-id ENSG00000141510 --external-db UniProt --output uniprot_map.json
uv run scripts/ensembl_api.py map-id ENST00000269305 --external-db RefSeq_mRNA --output refseq_map.json
```

**3. Get Genomic Sequence** — Fetch raw DNA for a coordinate window. Supports
GRCh37 via `--assembly GRCh37`.

```bash
uv run scripts/ensembl_api.py get-sequence 17:7661779-7687550 --species human --output seq.txt
uv run scripts/ensembl_api.py get-sequence chr9:21971100-21971200 --assembly GRCh37 --output seq_grch37.txt
```

**4. Gene Summary** — Hig