gh-k-dense-ai-claude-scientific-skills-scientific-skills/skills/gene-database/references/api_reference.md

NCBI Gene API Reference

This document provides detailed API documentation for accessing NCBI Gene database programmatically.

Table of Contents

1. E-utilities API
2. NCBI Datasets API
3. Authentication and Rate Limits
4. Error Handling

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E-utilities API

E-utilities (Entrez Programming Utilities) provide a stable interface to NCBI's Entrez databases.

Base URL

https://eutils.ncbi.nlm.nih.gov/entrez/eutils/

Common Parameters

• db - Database name (use gene for Gene database)
• api_key - API key for higher rate limits
• retmode - Return format (json, xml, text)
• retmax - Maximum number of records to return

ESearch - Search Database

Search for genes matching a text query.

Endpoint: esearch.fcgi

Parameters:

• db=gene (required) - Database to search
• term (required) - Search query
• retmax - Maximum results (default: 20)
• retmode - json or xml (default: xml)
• usehistory=y - Store results on history server for large result sets

Query Syntax:

• Gene symbol: BRCA1[gene] or BRCA1[gene name]
• Organism: human[organism] or 9606[taxid]
• Combine terms: BRCA1[gene] AND human[organism]
• Disease: muscular dystrophy[disease]
• Chromosome: 17q21[chromosome]
• GO terms: GO:0006915[biological process]

Example Request:

curl "https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi?db=gene&term=BRCA1[gene]+AND+human[organism]&retmode=json"

Response Format (JSON):

{
  "esearchresult": {
    "count": "1",
    "retmax": "1",
    "retstart": "0",
    "idlist": ["672"],
    "translationset": [],
    "querytranslation": "BRCA1[Gene Name] AND human[Organism]"
  }
}

ESummary - Document Summaries

Retrieve document summaries for Gene IDs.

Endpoint: esummary.fcgi

Parameters:

• db=gene (required) - Database
• id (required) - Comma-separated Gene IDs (up to 500)
• retmode - json or xml (default: xml)

Example Request:

curl "https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esummary.fcgi?db=gene&id=672&retmode=json"

Response Format (JSON):

{
  "result": {
    "672": {
      "uid": "672",
      "name": "BRCA1",
      "description": "BRCA1 DNA repair associated",
      "organism": {
        "scientificname": "Homo sapiens",
        "commonname": "human",
        "taxid": 9606
      },
      "chromosome": "17",
      "geneticsource": "genomic",
      "maplocation": "17q21.31",
      "nomenclaturesymbol": "BRCA1",
      "nomenclaturename": "BRCA1 DNA repair associated"
    }
  }
}

EFetch - Full Records

Fetch detailed gene records in various formats.

Endpoint: efetch.fcgi

Parameters:

• db=gene (required) - Database
• id (required) - Comma-separated Gene IDs
• retmode - xml, text, asn.1 (default: xml)
• rettype - gene_table, docsum

Example Request:

curl "https://eutils.ncbi.nlm.nih.gov/entrez/eutils/efetch.fcgi?db=gene&id=672&retmode=xml"

XML Response: Contains detailed gene information including:

• Gene nomenclature
• Sequence locations
• Transcript variants
• Protein products
• Gene Ontology annotations
• Cross-references
• Publications

ELink - Related Records

Find related records in Gene or other databases.

Endpoint: elink.fcgi

Parameters:

• dbfrom=gene (required) - Source database
• db (required) - Target database (gene, nuccore, protein, pubmed, etc.)
• id (required) - Gene ID(s)

Example Request:

# Get related PubMed articles
curl "https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=gene&db=pubmed&id=672&retmode=json"

EInfo - Database Information

Get information about the Gene database.

Endpoint: einfo.fcgi

Parameters:

• db=gene - Database to query

Example Request:

curl "https://eutils.ncbi.nlm.nih.gov/entrez/eutils/einfo.fcgi?db=gene&retmode=json"

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NCBI Datasets API

The Datasets API provides streamlined access to gene data with metadata and sequences.

Base URL

https://api.ncbi.nlm.nih.gov/datasets/v2alpha/gene

Authentication

Include API key in request headers:

api-key: YOUR_API_KEY

Get Gene by ID

Retrieve gene data by Gene ID.

Endpoint: GET /gene/id/{gene_id}

Example Request:

curl "https://api.ncbi.nlm.nih.gov/datasets/v2alpha/gene/id/672"

Response Format (JSON):

{
  "genes": [
    {
      "gene": {
        "gene_id": "672",
        "symbol": "BRCA1",
        "description": "BRCA1 DNA repair associated",
        "tax_name": "Homo sapiens",
        "taxid": 9606,
        "chromosomes": ["17"],
        "type": "protein-coding",
        "synonyms": ["BRCC1", "FANCS", "PNCA4", "RNF53"],
        "nomenclature_authority": {
          "authority": "HGNC",
          "identifier": "HGNC:1100"
        },
        "genomic_ranges": [
          {
            "accession_version": "NC_000017.11",
            "range": [
              {
                "begin": 43044295,
                "end": 43170245,
                "orientation": "minus"
              }
            ]
          }
        ],
        "transcripts": [
          {
            "accession_version": "NM_007294.4",
            "length": 7207
          }
        ]
      }
    }
  ]
}

Get Gene by Symbol

Retrieve gene data by symbol and organism.

Endpoint: GET /gene/symbol/{symbol}/taxon/{taxon}

Parameters:

• {symbol} - Gene symbol (e.g., BRCA1)
• {taxon} - Taxon ID (e.g., 9606 for human)

Example Request:

curl "https://api.ncbi.nlm.nih.gov/datasets/v2alpha/gene/symbol/BRCA1/taxon/9606"

Get Multiple Genes

Retrieve data for multiple genes.

Endpoint: POST /gene/id

Request Body:

{
  "gene_ids": ["672", "7157", "5594"]
}

Example Request:

curl -X POST "https://api.ncbi.nlm.nih.gov/datasets/v2alpha/gene/id" \
  -H "Content-Type: application/json" \
  -d '{"gene_ids": ["672", "7157", "5594"]}'

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Authentication and Rate Limits

Obtaining an API Key

1. Create an NCBI account at https://www.ncbi.nlm.nih.gov/account/
2. Navigate to Settings → API Key Management
3. Generate a new API key
4. Include the key in requests

Rate Limits

E-utilities:

• Without API key: 3 requests/second
• With API key: 10 requests/second

Datasets API:

• Without API key: 5 requests/second
• With API key: 10 requests/second

Usage Guidelines

1. Include email in requests: Add &email=your@email.com to E-utilities requests
2. Implement rate limiting: Use delays between requests
3. Use POST for large queries: When working with many IDs
4. Cache results: Store frequently accessed data locally
5. Handle errors gracefully: Implement retry logic with exponential backoff

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Error Handling

HTTP Status Codes

• 200 OK - Successful request
• 400 Bad Request - Invalid parameters or malformed query
• 404 Not Found - Gene ID or symbol not found
• 429 Too Many Requests - Rate limit exceeded
• 500 Internal Server Error - Server error (retry with backoff)

E-utilities Error Messages

E-utilities return errors in the response body:

XML format:

<ERROR>Empty id list - nothing to do</ERROR>

JSON format:

{
  "error": "Invalid db name"
}

Common Errors

1. Empty Result Set

   • Cause: Gene symbol or ID not found
   • Solution: Verify spelling, check organism filter

2. Rate Limit Exceeded

   • Cause: Too many requests
   • Solution: Add delays, use API key

3. Invalid Query Syntax

   • Cause: Malformed search term
   • Solution: Use proper field tags (e.g., [gene], [organism])

4. Timeout

   • Cause: Large result set or slow connection
   • Solution: Use History Server, reduce result size

Retry Strategy

Implement exponential backoff for failed requests:

import time

def retry_request(func, max_attempts=3):
    for attempt in range(max_attempts):
        try:
            return func()
        except Exception as e:
            if attempt < max_attempts - 1:
                wait_time = 2 ** attempt  # 1s, 2s, 4s
                time.sleep(wait_time)
            else:
                raise

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Common Taxon IDs

Organism	Scientific Name	Taxon ID
Human	Homo sapiens	9606
Mouse	Mus musculus	10090
Rat	Rattus norvegicus	10116
Zebrafish	Danio rerio	7955
Fruit fly	Drosophila melanogaster	7227
C. elegans	Caenorhabditis elegans	6239
Yeast	Saccharomyces cerevisiae	4932
Arabidopsis	Arabidopsis thaliana	3702
E. coli	Escherichia coli	562

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Additional Resources

• E-utilities Documentation: https://www.ncbi.nlm.nih.gov/books/NBK25501/
• Datasets API Documentation: https://www.ncbi.nlm.nih.gov/datasets/docs/v2/
• Gene Database Help: https://www.ncbi.nlm.nih.gov/gene/
• API Key Registration: https://www.ncbi.nlm.nih.gov/account/