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📄 / / profiles / r-and-d / raw_evidence / OpenAI4S / skills / bioskills / bio-database-access-entrez-search / SKILL.md

name: bio-entrez-search description: Search NCBI databases using Biopython Bio.Entrez (ESearch, EInfo, EGQuery, ESpell). Use when finding records by keyword, building reproducible field-qualified queries, navigating the Entrez Query Translator, exploiting the history server for large result sets, handling retmax caps, or interpreting weekly index lag. Covers PubMed, Nucleotide, Protein, Gene, SRA, GEO, Assembly, Taxonomy, ClinVar, dbSNP. origin: openai4s category: bioskills/database-access metadata: tool_type: python primary_tool: Bio.Entrez third_party: name: GPTomics/bioSkills repository: https://github.com/GPTomics/bioSkills commit: d91ed3d563019e649dc854c56ccd62551359488a license: MIT


Version Compatibility

Reference examples tested with: BioPython 1.83+, Entrez Direct 21.0+

Before using code patterns, verify installed versions match. If versions differ: - Python: pip show biopython then help(Bio.Entrez.esearch) to check signatures - CLI: esearch -version then esearch -help to confirm flags

If code throws ImportError, AttributeError, or TypeError, introspect the installed package and adapt the example to match the actual API rather than retrying.

Entrez Search

"Find NCBI records matching a query" -> ESearch returns matching record UIDs (not full records) from one NCBI database; EGQuery returns counts across all databases; EInfo describes a database's searchable fields and update timestamp.

The single most important fact: ESearch returns UIDs (PMIDs, GI numbers, gene IDs, etc.), not records. To get content the agent must call EFetch or ESummary. Forgetting this is the most common Entrez mistake.

Required Setup

from Bio import Entrez
import time

Entrez.email = 'researcher@institution.edu'  # NCBI requires; sets User-Agent
Entrez.api_key = 'YOUR_KEY'                  # 3 -> 10 req/sec; get at ncbi.nlm.nih.gov/account/settings/
Entrez.tool = 'project-name'                 # appears in NCBI usage logs; helps if rate-throttled

What ESearch actually does

ESearch sends the query string through the Entrez Query Translator (EQT), which rewrites unqualified terms into the canonical term[field] form, then runs the rewritten query against the per-database index. The result is a list of UIDs plus a QueryTranslation string showing exactly what was searched. Reproducible work always inspects QueryTranslation and builds queries that are translation-stable from the start.

handle = Entrez.esearch(db='nucleotide', term='human BRCA1')
record = Entrez.read(handle)
handle.close()
print(record['QueryTranslation'])
# '("homo sapiens"[Organism] OR human[All Fields]) AND (BRCA1[Gene Name] OR BRCA1[All Fields])'

The translator may expand human to the full taxonomy subtree, or coerce a gene symbol to [All Fields] if the symbol isn't unambiguous. Use field-qualified terms (Homo sapiens[ORGN] AND BRCA1[Gene Name]) for any query that will be re-run later.

Decision table: which utility for which question

Question Utility Returns Cost
"How many records match X in PubMed?" ESearch with retmax=0 Count + WebEnv 1 call
"Give me 20 matching UIDs" ESearch UIDs 1 call
"Give me ALL matching UIDs (>10K)" ESearch + usehistory='y' WebEnv/QueryKey 1 call (then EFetch chunks server-side)
"Does record X exist in db Y?" ESearch with term='X[Accn]' UIDs 1 call
"Which NCBI databases mention X at all?" EGQuery Counts across every db 1 call
"What searchable fields does db Y have?" EInfo with db=Y FieldList 1 call
"Last update timestamp for db Y?" EInfo with db=Y LastUpdate 1 call
"Did the user misspell X?" ESpell Spelling suggestion 1 call

EGQuery has been semi-deprecated since the 2022 site refactor — it still works but counts can lag the per-database indexes by 1-2 days. For authoritative cross-database counts, loop ESearch over a curated db list instead.

retmax silent caps

Endpoint behavior Cap Workaround
Default retmax 20 Set explicitly
Legacy esearch.fcgi (no usehistory) 9,999 silent cap Use history server
usehistory='y' + ESearch 100,000 per page Page with retstart against the WebEnv
EPost (to push IDs server-side) 200 IDs per call Chunk to multiple EPost calls; union with QueryKey

The 9,999 cap is the bug that has shipped in countless lab pipelines: query returns "Count: 78,432" but IdList has 9,999 entries and there is no error. Always set retmax explicitly and either page or move to usehistory='y' whenever Count > retmax.

History server (WebEnv/QueryKey) semantics

Property Value
TTL 8 hours absolute (per NCBI E-utils help, 2024)
Idle eviction Empirically ~15 min under load; can be shorter
Chaining Run another ESearch against WebEnv with term='#1 AND #2' to intersect prior QueryKeys
Persistence Session is per WebEnv string; do NOT share across processes when isolation matters
Failure mode Expired session returns HTTP 200 with <ERROR>WebEnv not found</ERROR> — must parse body, not status

Chaining example:

h1 = Entrez.esearch(db='pubmed', term='CRISPR[Title]', usehistory='y')
r1 = Entrez.read(h1); h1.close()
webenv = r1['WebEnv']

h2 = Entrez.esearch(db='pubmed', term='2024[PDAT]', usehistory='y', WebEnv=webenv)
r2 = Entrez.read(h2); h2.close()

# Intersect QueryKey #1 (CRISPR) AND #2 (2024) into a new key
h3 = Entrez.esearch(db='pubmed', term=f'#{r1["QueryKey"]} AND #{r2["QueryKey"]}',
                    usehistory='y', WebEnv=webenv)
r3 = Entrez.read(h3); h3.close()
print(f'CRISPR & 2024: {r3["Count"]}')

Index lag

NCBI's Entrez indexer runs nightly (US Eastern). Records submitted Monday morning typically appear in ESearch results Wednesday at earliest. PubMed has additional MEDLINE indexing lag (1-3 weeks for full MeSH terms). For freshly-deposited data the more reliable check is EFetch on the known accession or NCBI Datasets API for genomes.

Field-qualified query patterns (per database)

Database Common fields Notes
pubmed [Title], [TIAB] (title+abstract), [MeSH], [Author], [Journal], [PDAT], [DCOM], [PMC] [TIAB] is more permissive than [Title]; [MeSH] requires the term to be indexed (lags)
nucleotide [Organism], [Gene Name], [Accn], [SLEN], [Filter], [PROP] srcdb_refseq[PROP] restricts to RefSeq; biomol_genomic[PROP] filters molecule type
protein [Organism], [Gene Name], [Accn], [MOLWT], [PROP] swissprot[Filter] restricts to reviewed
gene [Gene/Locus], [Organism], [Chromosome], [Gene Type] [Gene Type] includes protein-coding, pseudo, ncRNA
sra [Organism], [Platform], [Strategy], [Library Source], [BioProject] [Strategy] accepts RNA-Seq, WGS, ChIP-Seq, etc.
gds (GEO) [Organism], [Entry Type], [GDS Type], [Platform] gse[Entry Type] for Series, gds[Entry Type] for curated DataSets
taxonomy [Scientific Name], [Common Name], [Rank], [TXID] TXID is the numeric taxonomy ID
clinvar [Gene Name], [Clinical Significance], [Variation Type] pathogenic[CLIN] for pathogenic only

Filter properties that newcomers miss

# Curated RefSeq mRNA only, human, between 500 and 5000 nt
term = 'Homo sapiens[ORGN] AND srcdb_refseq[PROP] AND biomol_mrna[PROP] AND 500:5000[SLEN]'

# Reviewed SwissProt human kinases
term = 'Homo sapiens[ORGN] AND swissprot[Filter] AND kinase[Protein Name]'

# PubMed: human studies in last 30 days, full-text in PMC
term = 'CRISPR[Title] AND humans[MeSH Terms] AND last 30 days[EDAT] AND pubmed pmc[sb]'

Organism field gotcha

[Organism] (and the alias [ORGN]) is taxonomy-walked: searching mammalia[ORGN] returns records from every species in Mammalia. To get records tagged at exactly that node use [Organism:exp] (no taxonomic expansion). Most workflows want the default walk, but multi-species queries that "blow up" by 100x are almost always a missing :exp.

Code patterns

Single search with explicit retmax

Goal: Get matching UIDs for a focused query without hitting silent caps.

Approach: Set retmax explicitly to the maximum the caller wants; if Count > retmax either page or switch to history server.

Reference (BioPython 1.83+):

def search_ncbi(db, term, max_results=100):
    handle = Entrez.esearch(db=db, term=term, retmax=max_results)
    record = Entrez.read(handle); handle.close()
    count = int(record['Count'])
    if count > max_results:
        print(f'WARNING: {count} matched, returning first {max_results}; use history server for full set')
    return record['IdList'], count, record['QueryTranslation']

Paged retrieval (only when enumeration without fetching is required)

Goal: Stream all matching UIDs to a file when downstream work can't use the history server.

Approach: Page through retstart increments; respect rate limit; stop at total.

def stream_all_ids(db, term, batch_size=10000):
    h = Entrez.esearch(db=db, term=term, retmax=0)
    total = int(Entrez.read(h)['Count']); h.close()
    delay = 0.1 if Entrez.api_key else 0.34
    for start in range(0, total, batch_size):
        h = Entrez.esearch(db=db, term=term, retstart=start, retmax=batch_size)
        r = Entrez.read(h); h.close()
        for uid in r['IdList']:
            yield uid
        time.sleep(delay)

For any download workflow, history-server retrieval is strictly better — see batch-downloads skill.

History server for downstream EFetch

Goal: Push a large result set to NCBI servers so EFetch can pull it in batches without re-sending IDs.

Approach: ESearch with usehistory='y'; capture WebEnv and QueryKey; pass to EFetch.

Reference (BioPython 1.83+):

h = Entrez.esearch(db='nucleotide',
                   term='Homo sapiens[ORGN] AND srcdb_refseq[PROP] AND biomol_mrna[PROP]',
                   usehistory='y', retmax=0)
r = Entrez.read(h); h.close()
webenv, query_key, count = r['WebEnv'], r['QueryKey'], int(r['Count'])
print(f'{count} mRNAs queued on history server; use webenv/query_key with efetch')

Inspect the translation before trusting a query

Goal: Catch translator misinterpretation before producing publication results.

Approach: Always print QueryTranslation for new queries and lock the rewritten string into the codebase as the canonical query.

h = Entrez.esearch(db='pubmed', term='covid vaccine efficacy 2024', retmax=0)
r = Entrez.read(h); h.close()
print(r['QueryTranslation'])
# '("covid 19 vaccines"[MeSH Terms] OR ("covid 19"[All Fields] AND ...
# Now use this rewritten string explicitly to guarantee reproducibility.

Discover fields for a database

def list_fields(db):
    h = Entrez.einfo(db=db); r = Entrez.read(h); h.close()
    return [(f['Name'], f['FullName'], f['Description']) for f in r['DbInfo']['FieldList']]

Spell-check before searching (catches typo-driven empty results)

h = Entrez.espell(db='pubmed', term='breast canser')
r = Entrez.read(h); h.close()
print(r['CorrectedQuery'])  # 'breast cancer'

Failure modes

Silent retmax cap

Query translation mismatch

WebEnv expiration mid-pipeline

Index lag for fresh deposits

Organism over-expansion

Empty IdList with no error

Rate-limit math

Auth req/sec allowed Sleep between calls Bulk-friendly?
Email only 3 0.34 s Use history server, not parallel calls
Email + API key 10 0.10 s Modest parallelism (4 workers) is safe
Institutional bulk Email eutilities@ncbi.nlm.nih.gov Negotiated For >100K queries; courtesy expected

NCBI's terms of use ask that heavy automated queries run outside US weekday business hours (9 AM-5 PM ET). For genuinely bulk work, prefer the history server over parallel API calls — chunking against one session is faster and friendlier than scaling out.

Common errors

Error / symptom Cause Solution
HTTPError 429 Rate limit exceeded Add time.sleep(0.34) or use API key
HTTPError 400 Field name or bracket malformed Inspect EInfo field list; check brackets
RuntimeError: ... email Missing Entrez.email Set globally before any call
Empty IdList, large Count Hit retmax cap Set retmax explicitly or use history
<ERROR>WebEnv not found</ERROR> (HTTP 200) Session expired Re-run ESearch; parse XML body for errors
Query gives wildly wrong count EQT misinterpretation Print QueryTranslation; use field-qualified terms

References