bio-entrez-link

name	bio-entrez-link
description	Find cross-references between NCBI databases using Biopython Bio.Entrez. Use when navigating from genes to proteins, sequences to publications, finding related records, or discovering database relationships.
tool_type	python
primary_tool	Bio.Entrez

Entrez Link

Navigate between NCBI databases using Biopython's Entrez module (ELink utility).

Required Setup

from Bio import Entrez

Entrez.email = '[e-mail]'  # Required by NCBI
Entrez.api_key = 'your_api_key'          # Optional, raises rate limit

Core Function

Entrez.elink() - Cross-Database Links

Find related records in the same or different databases.

# Find proteins linked to a gene
handle = Entrez.elink(dbfrom='gene', db='protein', id='672')
record = Entrez.read(handle)
handle.close()

# Extract linked IDs
linkset = record[0]
if linkset['LinkSetDb']:
    links = linkset['LinkSetDb'][0]['Link']
    protein_ids = [link['Id'] for link in links]
    print(f"Found {len(protein_ids)} linked proteins")

Key Parameters:

Parameter	Description	Example
dbfrom	Source database	'gene'
db	Target database	'protein'
id	Source record ID(s)	'672' or '672,675'
linkname	Specific link type	'gene_protein_refseq'
cmd	Link command	'neighbor', 'neighbor_score'

ELink Result Structure

record[0]                          # First linkset
record[0]['DbFrom']                # Source database
record[0]['IdList']                # Input IDs
record[0]['LinkSetDb']             # List of link results
record[0]['LinkSetDb'][0]['DbTo']  # Target database
record[0]['LinkSetDb'][0]['LinkName']  # Link name
record[0]['LinkSetDb'][0]['Link']  # List of linked records
record[0]['LinkSetDb'][0]['Link'][0]['Id']  # Linked ID

Common Link Paths

Gene to Other Databases

From	To	Link Name	Description
gene	protein	gene_protein	All proteins
gene	protein	gene_protein_refseq	RefSeq proteins only
gene	nucleotide	gene_nuccore	Nucleotide sequences
gene	nucleotide	gene_nuccore_refseqrna	RefSeq mRNA
gene	pubmed	gene_pubmed	Related publications
gene	homologene	gene_homologene	Homologs
gene	snp	gene_snp	SNPs in gene
gene	clinvar	gene_clinvar	Clinical variants

Nucleotide to Other Databases

From	To	Link Name	Description
nucleotide	protein	nuccore_protein	Encoded proteins
nucleotide	gene	nuccore_gene	Gene records
nucleotide	pubmed	nuccore_pubmed	Publications
nucleotide	taxonomy	nuccore_taxonomy	Organism taxonomy
nucleotide	biosample	nuccore_biosample	Sample info
nucleotide	sra	nuccore_sra	Related SRA data

Protein to Other Databases

From	To	Link Name	Description
protein	nucleotide	protein_nuccore	Coding sequences
protein	gene	protein_gene	Gene records
protein	pubmed	protein_pubmed	Publications
protein	structure	protein_structure	3D structures
protein	cdd	protein_cdd	Conserved domains

PubMed Links

From	To	Link Name	Description
pubmed	pubmed	pubmed_pubmed	Related articles
pubmed	gene	pubmed_gene	Mentioned genes
pubmed	protein	pubmed_protein	Mentioned proteins
pubmed	nucleotide	pubmed_nuccore	Mentioned sequences

Code Patterns

Gene to Protein

from Bio import Entrez

Entrez.email = '[e-mail]'

def get_proteins_for_gene(gene_id):
    handle = Entrez.elink(dbfrom='gene', db='protein', id=gene_id, linkname='gene_protein_refseq')
    record = Entrez.read(handle)
    handle.close()

    if not record[0]['LinkSetDb']:
        return []
    return [link['Id'] for link in record[0]['LinkSetDb'][0]['Link']]

protein_ids = get_proteins_for_gene('672')  # BRCA1
print(f"RefSeq proteins: {protein_ids[:5]}")

Nucleotide to Gene

def get_gene_for_nucleotide(nuc_id):
    handle = Entrez.elink(dbfrom='nucleotide', db='gene', id=nuc_id)
    record = Entrez.read(handle)
    handle.close()

    if not record[0]['LinkSetDb']:
        return None
    return record[0]['LinkSetDb'][0]['Link'][0]['Id']

gene_id = get_gene_for_nucleotide('NM_007294')
print(f"Gene ID: {gene_id}")

Find Related PubMed Articles

def get_related_articles(pmid, max_results=10):
    handle = Entrez.elink(dbfrom='pubmed', db='pubmed', id=pmid, linkname='pubmed_pubmed')
    record = Entrez.read(handle)
    handle.close()

    if not record[0]['LinkSetDb']:
        return []
    links = record[0]['LinkSetDb'][0]['Link']
    return [link['Id'] for link in links[:max_results]]

related = get_related_articles('35412348')
print(f"Related articles: {related}")

Get All Available Links

def discover_links(db, record_id):
    handle = Entrez.elink(dbfrom=db, id=record_id, cmd='acheck')
    record = Entrez.read(handle)
    handle.close()

    links = {}
    for linkset in record[0].get('LinkSetDb', []):
        links[linkset['LinkName']] = linkset['DbTo']
    return links

available = discover_links('gene', '672')
for name, target in available.items():
    print(f"{name} -> {target}")

Navigate Gene -> Protein -> Structure

def gene_to_structures(gene_id):
    # Gene to protein
    handle = Entrez.elink(dbfrom='gene', db='protein', id=gene_id, linkname='gene_protein_refseq')
    record = Entrez.read(handle)
    handle.close()

    if not record[0]['LinkSetDb']:
        return []
    protein_ids = [link['Id'] for link in record[0]['LinkSetDb'][0]['Link'][:5]]

    # Protein to structure
    handle = Entrez.elink(dbfrom='protein', db='structure', id=','.join(protein_ids))
    record = Entrez.read(handle)
    handle.close()

    structure_ids = []
    for linkset in record:
        if linkset['LinkSetDb']:
            structure_ids.extend([link['Id'] for link in linkset['LinkSetDb'][0]['Link']])
    return structure_ids

structures = gene_to_structures('672')
print(f"Structure IDs: {structures[:5]}")

Link Multiple IDs at Once

def batch_link(dbfrom, db, ids):
    if isinstance(ids, list):
        ids = ','.join(ids)

    handle = Entrez.elink(dbfrom=dbfrom, db=db, id=ids)
    record = Entrez.read(handle)
    handle.close()

    # Returns one linkset per input ID
    results = {}
    for linkset in record:
        source_id = linkset['IdList'][0]
        linked_ids = []
        if linkset['LinkSetDb']:
            linked_ids = [link['Id'] for link in linkset['LinkSetDb'][0]['Link']]
        results[source_id] = linked_ids
    return results

results = batch_link('gene', 'protein', ['672', '675', '7157'])
for gene, proteins in results.items():
    print(f"Gene {gene}: {len(proteins)} proteins")

Get Publications for a Sequence

def get_sequence_publications(accession):
    # First get the GI/UID
    handle = Entrez.esearch(db='nucleotide', term=f'{accession}[accn]')
    search = Entrez.read(handle)
    handle.close()

    if not search['IdList']:
        return []
    uid = search['IdList'][0]

    # Link to PubMed
    handle = Entrez.elink(dbfrom='nucleotide', db='pubmed', id=uid)
    record = Entrez.read(handle)
    handle.close()

    if not record[0]['LinkSetDb']:
        return []
    return [link['Id'] for link in record[0]['LinkSetDb'][0]['Link']]

pmids = get_sequence_publications('NM_007294')
print(f"PubMed IDs: {pmids[:5]}")

Link Commands

Command	Description
neighbor	Default - get linked records
neighbor_score	Include relevance scores
neighbor_history	Store results in history
acheck	List all available links
ncheck	Check if any links exist
lcheck	Check specific link exists
llinks	Get URLs to Entrez links
prlinks	Get provider links (external)

Common Errors

Error	Cause	Solution
Empty LinkSetDb	No links exist	Check if record has linked data
HTTPError 400	Invalid ID or database	Verify ID exists in source database
KeyError	Missing expected field	Check if LinkSetDb is empty first
Single linkset expected, got list	Multiple input IDs	Iterate through record list

Decision Tree

Need to find related records?
├── Know what link you want?
│   └── Use elink with specific linkname
├── Discover what links exist?
│   └── Use elink with cmd='acheck'
├── Navigate to target database?
│   └── Use elink(dbfrom=X, db=Y, id=Z)
├── Find related records in same database?
│   └── Use elink(dbfrom=X, db=X) with neighbor
├── Chain multiple databases?
│   └── Call elink multiple times
└── Need the actual records?
    └── Use elink first, then efetch with IDs

Related Skills

• entrez-search - Search databases before linking
• entrez-fetch - Retrieve records after finding linked IDs
• batch-downloads - Download many linked records efficiently