@mims-harvard/tooluniverse-sequence-retrieval
Router skill for ToolUniverse tasks. First checks if specialized tooluniverse skills (105+ skills covering disease/drug/target research, gene-disease associations, clinical decision support, genomics, epigenomics, proteomics, comparative genomics, chemical safety, toxicology, systems biology, and more) can solve the problem, then falls back to general strategies for using 2300+ scientific tools. Covers tool discovery, multi-hop queries, comprehensive research workflows, disambiguation, evidence grading, and report generation. Use when users need to research any scientific topic, find biological data, or explore drug/target/disease relationships. ALSO USE for any biology, medicine, chemistry, pharmacology, or life science question — even simple factoid questions like "how many X in protein Y", "what drug interacts with Z", "what gene causes disease W", or "translate this sequence". These questions benefit from database lookups (UniProt, PubMed, ChEMBL, ClinVar, GWAS Catalog, etc.) rather than answering from memory alone. When in doubt about a scientific fact, USE THIS SKILL to verify against real databases.
| name | tooluniverse-sequence-retrieval |
| description | Retrieve DNA/RNA/protein sequences from NCBI and ENA with disambiguation. Quality hierarchy: RefSeq (NM_/NP_) > RefSeq predicted (XM_/XP_) > GenBank submissions. Use for fetching specific sequences by accession, gene-symbol-to-sequence lookup, transcript-isoform retrieval, and curated-vs-raw-submission preference. |
| disable-model-invocation | true |
Biological Sequence Retrieval
Retrieve DNA, RNA, and protein sequences with proper disambiguation and cross-database handling.
IMPORTANT: Always use English terms in tool calls. Only try original-language terms as fallback. Respond in the user's language.
LOOK UP DON'T GUESS: Never assume accession numbers or sequence versions. Always retrieve and verify from NCBI or ENA.
Domain Reasoning
Sequence quality hierarchy: RefSeq (NM_/NP_ = curated) > RefSeq predicted (XM_/XP_) > GenBank (submitted). Prefer the MANE Select transcript for human canonical isoforms. Check version numbers -- annotations improve across versions.
Workflow
Phase 0: Clarify (if needed) → Phase 1: Disambiguate Gene/Organism → Phase 2: Search & Retrieve → Phase 3: Report
Phase 0: Clarification (When Needed)
Ask ONLY if: gene exists in multiple organisms, sequence type unclear, or strain matters. Skip for: specific accessions, clear organism+gene combos, complete genome requests with organism.
Phase 1: Gene/Organism Disambiguation
Accession Type Decision Tree
| Prefix | Type | Use With |
|---|---|---|
| NC_/NM_/NR_/NP_/XM_ | RefSeq | NCBI only |
| U*/M*/K*/X*/CP*/NZ_ | GenBank | NCBI or ENA |
| EMBL format | EMBL | ENA preferred |
CRITICAL: Never try ENA tools with RefSeq accessions -- they return 404.
Identity Checklist
- Organism confirmed (scientific name)
- Gene symbol/name identified
- Sequence type determined (genomic/mRNA/protein)
- Accession prefix identified for tool selection
Phase 2: Data Retrieval (Internal)
Retrieve silently. Do NOT narrate the search process.
# Search NCBI Nucleotide
result = tu.tools.NCBI_search_nucleotide(
operation="search", organism=organism, gene=gene,
strain=strain, keywords=keywords, seq_type=seq_type, limit=10
)
# Get accessions from UIDs
accessions = tu.tools.NCBI_fetch_accessions(operation="fetch_accession", uids=result["data"]["uids"])
# Retrieve sequence (FASTA or GenBank format)
sequence = tu.tools.NCBI_get_sequence(operation="fetch_sequence", accession=accession, format="fasta")
# ENA alternative (non-RefSeq accessions only)
entry = tu.tools.ena_get_entry(accession=accession)
fasta = tu.tools.ena_get_sequence_fasta(accession=accession)
Fallback Chains
| Primary | Fallback | Notes |
|---|---|---|
| NCBI_get_sequence | ENA (if GenBank format) | NCBI unavailable |
| ena_get_entry | NCBI_get_sequence | ENA doesn't have RefSeq |
| NCBI_search_nucleotide | Try broader keywords | No results |
Phase 3: Report Sequence Profile
Present as a Sequence Profile Report. Hide search process. Include:
- Search Summary: query, database, result count
- Primary Sequence: accession, type (RefSeq/GenBank), organism, strain, length, molecule, topology, curation level
- Sequence Preview: first lines of FASTA (truncated)
- Annotations Summary: CDS/tRNA/rRNA/regulatory feature counts (from GenBank format)
- Alternative Sequences: ranked by relevance and curation, with ENA compatibility
- Cross-Database References: RefSeq, GenBank, ENA/EMBL, BioProject, BioSample
- Download Options: FASTA (for BLAST/alignment), GenBank (for annotation)
Curation Level Tiers
| Tier | Prefix | Description |
|---|---|---|
| RefSeq Reference (best) | NC_, NM_, NP_ | NCBI-curated, gold standard |
| RefSeq Predicted | XM_, XP_, XR_ | Computationally predicted |
| GenBank Validated | Various | Submitted, some curation |
| GenBank Direct | Various | Direct submission |
| Third Party | TPA_ | Third-party annotation |
Reasoning Framework
Sequence quality: Prefer RefSeq over GenBank. Check version numbers. Sequences with "PREDICTED" in definition are not experimentally validated.
Accession guidance: RefSeq = NCBI-only. GenBank = mirrored in ENA/EMBL. Default to RefSeq mRNA (NM_) for human/model organisms; most complete genome assembly for microbial queries.
Cross-database reconciliation: Same sequence may have different accessions (e.g., GenBank U00096 = RefSeq NC_000913 for E. coli K-12). Always report both when available. Discrepancies between GenBank/RefSeq typically indicate RefSeq curation corrected submission errors.
Synthesis Questions
- What is the highest-quality accession available?
- Are there alternative accessions in other databases?
- What is the annotation completeness?
- Is the sequence from the expected organism/strain?
- What download format suits the user's downstream analysis?
Error Handling
| Error | Response |
|---|---|
| "No search criteria provided" | Add organism, gene, or keywords |
| "ENA 404 error" | Likely RefSeq -- use NCBI only |
| "No results found" | Broaden search, check spelling, try synonyms |
| "Sequence too large" | Note size, provide download link instead |
Tool Reference
NCBI Tools: NCBI_search_nucleotide (search), NCBI_fetch_accessions (UID→accession), NCBI_get_sequence (retrieve)
ENA Tools (GenBank/EMBL only): ena_get_entry (metadata), ena_get_sequence_fasta (FASTA), ena_get_entry_summary (summary)
Search Parameters Reference
NCBI_search_nucleotide: operation="search", organism (scientific name), gene (symbol), strain, keywords, seq_type (complete_genome/mrna/refseq), limit
NCBI_get_sequence: operation="fetch_sequence", accession, format (fasta/genbank)
Loading...
Select a file to preview
Analyzing security...
Checking scan reports and verification data.
Bill of Materials
Everything this skill can do — files, network, commands, and more.