--- name: ensembl-database-bb88430ca5fb 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 LICENSE_NOTIFICATION.txt does not already exist in this skill 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** — High-level metadata: symbol, biotype, description, chromosomal location. ```bash uv run scripts/ensembl_api.py gene-summary ENSG00000141510 --output gene_summary.json ``` **5. List Transcripts** — All transcripts for a gene, with optional `--only-mane` or `--only-canonical` filters. Output includes Transcript Support Level (TSL). ```bash uv run scripts/ensembl_api.py transcripts ENSG00000141510 --only-mane --output transcripts_mane.json uv run scripts/ensembl_api.py transcripts ENSG00000141510 --only-canonical --output transcripts_canonical.json uv run scripts/ensembl_api.py transcripts ENSG00000141510 --output transcripts_all.json ``` **5b. Canonical TSS** — Get the single coordinate of the Transcription Start Site (TSS) for the canonical transcript of a gene. > [!NOTE] Unlike the standard `transcripts` command, `canonical-tss` accepts > both symbols (e.g., `TP53`) and Ensembl IDs, and automatically resolves them. > It also does the math for strand orientation (TSS is `Start` for `+` strand > and `End` for `-` strand), outputting the single integer coordinate directly. ```bash uv run scripts/ensembl_api.py canonical-tss TP53 --output tp53_tss.json uv run scripts/ensembl_api.py canonical-tss ENSG00000141510 --output tss.json ``` **6. Transcript Structure** — Exon coordinates, CDS boundaries, and computed 5'/3' UTR regions for a transcript. ```bash uv run scripts/ensembl_api.py transcript-structure ENST00000269305 --output structure.json ``` **7. Protein Info** — ENSP ID and sequence length for a transcript. ```bash uv run scripts/ensembl_api.py protein-info ENST00000269305 --output protein_info.json ``` **8. Protein Sequence** — Amino acid FASTA for a transcript (ENST) or protein (ENSP) ID. ```bash uv run scripts/ensembl_api.py protein-sequence ENST00000269305 --output protein.fasta uv run scripts/ensembl_api.py protein-sequence ENSP00000269305 --output protein_ensp.fasta ``` **9. Variant Consequence (VEP)** — Predict molecular consequences for a genomic variant. Includes open-licensed plugins: AlphaMissense, Conservation, DosageSensitivity, IntAct, MaveDB, OpenTargets, LoF (Loftee), NMD, UTRAnnotator, mutfunc, LOEUF. ```bash uv run scripts/ensembl_api.py vep 9:21971147:T:C --species human --output vep.json uv run scripts/ensembl_api.py vep rs699 --species human --output vep_rs699.json ``` Example VEP stdout output: ``` [*] Variant: 9:21971147:T>C [*] Most severe consequence: missense_variant [*] Found 15 transcript consequences. [*] VEP Predictions: - ENST00000304494 (CDKN2A): Consequence = missense_variant - ENST00000304494 (CDKN2A): Amino Acids = N/S - ENST00000304494 (CDKN2A): SIFT = deleterious (0.01) - ENST00000304494 (CDKN2A): AlphaMissense Class = likely_benign - ENST00000304494 (CDKN2A): AlphaMissense Pathogenicity = 0.2129 - ENST00000304494 (CDKN2A): Conservation = 2.05 - ENST00000304494 (CDKN2A): Dosage Sensitivity (Haplo) = 0.889228328567991 - ENST00000304494 (CDKN2A): Dosage Sensitivity (Triplo) = 0.135514349094646 - ENST00000304494 (CDKN2A): Loss of Function (LOEUF) = 0.791 ``` **Presenting VEP Results:** After running the VEP command, you MUST present the full VEP Predictions list from stdout to the user. This list contains both standard VEP predictions (Consequence, Amino Acids, SIFT, PolyPhen) and open-license plugin results (AlphaMissense, Conservation, Dosage Sensitivity, LOEUF, Loftee LoF, NMD, UTRAnnotator, Mutfunc). Do NOT just summarize — show the complete list so the user can see all predictions. If the list is very long (many transcripts), show the MANE Select / canonical transcript rows in full and note that the complete data is in the JSON output. ## Parsing Outputs If the user needs detailed, nested structural data (like the precise integer coordinates of Exon 2 of a transcript) that isn't summarized in stdout: 1. Locate the JSON file (either specified via `--output` or the temporary file path printed by the script). 2. Use terminal tools like `jq` or write a quick, disposable python snippet to extract the specific data point requested. Do **not** attempt to read the entire JSON file into your context if it is very large. ## Custom Queries If you need to make an API call that the script does not support (e.g., fetching protein domain annotations, coordinate mapping between assemblies, homology searches, linkage disequilibrium, or phenotype lookups), read `references/ensembl_rest_api_reference.md` for a complete reference of available endpoints, parameters, and response fields. **CRITICAL:** When writing custom scripts or using alternatives to the provided scripts, you **MUST** respect the Ensembl REST API rate limits (maximum 15 requests per second) and handle `429 Too Many Requests` errors gracefully (e.g., with exponential backoff). --- Source attribution: mkurman Original project: https://github.com/mkurman/zorai/blob/d06ee7597049567dab92db22d41b2764cf89094a/skills/scientific-skills-gdm/ensembl_database/SKILL.md License: Apache-2.0 License information: https://www.apache.org/licenses/LICENSE-2.0 Original upstream instructions; downloaded from Mega AI Hub. ## Upstream license notice Apache License Version 2.0, January 2004 http://www.apache.org/licenses/ TERMS AND CONDITIONS FOR USE, REPRODUCTION, AND DISTRIBUTION 1. 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See the License for the specific language governing permissions and limitations under the License. # Mega AI Hub resource metadata Creator / publisher: mkurman Original project: https://github.com/mkurman/zorai/blob/d06ee7597049567dab92db22d41b2764cf89094a/skills/scientific-skills-gdm/ensembl_database/SKILL.md Attribution basis: Source repository record Fields of work: Data & Analytics, Education & Research, Healthcare & Life Sciences Roles: Business Intelligence Analyst, Clinical Research, Data Scientist, Health Informatics, Researcher Specialties: API, Database Tools: Ensembl Rest Api Country applicability: Country not specified Classification basis: Source catalog labels Instruction SHA-256: c4585fce0e98e06ace94eea854defcd00d9e5ca4ac6923cb1ac7e246b34d92e7