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# NCBI Gene API Reference
This document provides detailed API documentation for accessing NCBI Gene database programmatically.
## Table of Contents
1. [E-utilities API](#e-utilities-api)
2. [NCBI Datasets API](#ncbi-datasets-api)
3. [Authentication and Rate Limits](#authentication-and-rate-limits)
4. [Error Handling](#error-handling)
---
## 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:**
```bash
curl "https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi?db=gene&term=BRCA1[gene]+AND+human[organism]&retmode=json"
```
**Response Format (JSON):**
```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:**
```bash
curl "https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esummary.fcgi?db=gene&id=672&retmode=json"
```
**Response Format (JSON):**
```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:**
```bash
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:**
```bash
# 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:**
```bash
curl "https://eutils.ncbi.nlm.nih.gov/entrez/eutils/einfo.fcgi?db=gene&retmode=json"
```
---
## 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:**
```bash
curl "https://api.ncbi.nlm.nih.gov/datasets/v2alpha/gene/id/672"
```
**Response Format (JSON):**
```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:**
```bash
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:**
```json
{
"gene_ids": ["672", "7157", "5594"]
}
```
**Example Request:**
```bash
curl -X POST "https://api.ncbi.nlm.nih.gov/datasets/v2alpha/gene/id" \
-H "Content-Type: application/json" \
-d '{"gene_ids": ["672", "7157", "5594"]}'
```
---
## 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
---
## 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:**
```xml
<ERROR>Empty id list - nothing to do</ERROR>
```
**JSON format:**
```json
{
"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:
```python
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
```
---
## 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 |
---
## 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/