Sequence Retrieval

name: tooluniverse-sequence-retrieval description: Retrieves biological sequences (DNA, RNA, protein) from NCBI and ENA with gene disambiguation, accession type handling, and comprehensive sequence profiles. Creates detailed reports with sequence metadata, cross-database references, and download options. Use when users need nucleotide sequences, protein sequences, genome data, or mention GenBank, RefSeq, EMBL accessions.

Biological Sequence Retrieval

Retrieve DNA, RNA, and protein sequences with proper disambiguation and cross-database handling.

IMPORTANT: Always use English terms in tool calls (gene names, organism names, sequence descriptions), even if the user writes in another language. Only try original-language terms as a fallback if English returns no results. Respond in the user's language.

Workflow Overview

Phase 0: Clarify (if needed)
    ↓
Phase 1: Disambiguate Gene/Organism
    ↓
Phase 2: Search & Retrieve (Internal)
    ↓
Phase 3: Report Sequence Profile

Phase 0: Clarification (When Needed)

Ask the user ONLY if:

• Gene name exists in multiple organisms (e.g., "BRCA1" → human or mouse?)
• Sequence type unclear (mRNA, genomic, protein?)
• Strain/isolate matters (e.g., E. coli → K-12, O157:H7, etc.)

Skip clarification for:

• Specific accession numbers (NC_*, NM_*, U*, etc.)
• Clear organism + gene combinations
• Complete genome requests with organism specified

Phase 1: Gene/Organism Disambiguation

1.1 Resolve Identifiers

from tooluniverse import ToolUniverse
tu = ToolUniverse()
tu.load_tools()

# Strategy depends on input type
if user_provided_accession:
    # Direct retrieval based on accession type
    accession = user_provided_accession
    
elif user_provided_gene_and_organism:
    # Search NCBI Nucleotide
    result = tu.tools.NCBI_search_nucleotide(
        operation="search",
        organism=organism,
        gene=gene,
        limit=10
    )

1.2 Accession Type Decision Tree

CRITICAL: Accession prefix determines which tools to use.

1.3 Identity Resolution Checklist

• Organism confirmed (scientific name)
• Gene symbol/name identified
• Sequence type determined (genomic/mRNA/protein)
• Strain specified (if relevant)
• Accession prefix identified → tool selection

Phase 2: Data Retrieval (Internal)

Retrieve silently. Do NOT narrate the search process.

2.1 Search for Sequences

# Search NCBI Nucleotide
result = tu.tools.NCBI_search_nucleotide(
    operation="search",
    organism=organism,
    gene=gene,
    strain=strain,  # Optional
    keywords=keywords,  # Optional
    seq_type=seq_type,  # complete_genome, mrna, refseq
    limit=10
)

# Get accession numbers from UIDs
accessions = tu.tools.NCBI_fetch_accessions(
    operation="fetch_accession",
    uids=result["data"]["uids"]
)

2.2 Retrieve Sequence Data

# Get sequence in desired format
sequence = tu.tools.NCBI_get_sequence(
    operation="fetch_sequence",
    accession=accession,
    format="fasta"  # or "genbank"
)

# GenBank format for annotations
annotations = tu.tools.NCBI_get_sequence(
    operation="fetch_sequence",
    accession=accession,
    format="genbank"
)

2.3 ENA Alternative (for GenBank/EMBL accessions)

# Only for non-RefSeq accessions!
if not accession.startswith(("NC_", "NM_", "NR_", "NP_", "XM_", "XR_")):
    # ENA entry info
    entry = tu.tools.ena_get_entry(accession=accession)
    
    # ENA FASTA
    fasta = tu.tools.ena_get_sequence_fasta(accession=accession)
    
    # ENA summary
    summary = tu.tools.ena_get_entry_summary(accession=accession)

Fallback Chains

Critical Rule: Never try ENA tools with RefSeq accessions (NC_, NM_, etc.) - they will return 404 errors.

Phase 3: Report Sequence Profile

Output Structure

Present as a Sequence Profile Report. Hide search process.

# Sequence Profile: [Gene/Organism]

**Search Summary**
- Query: [gene] in [organism]
- Database: NCBI Nucleotide
- Results: [N] sequences found

---

## Primary Sequence

### [Accession]: [Definition/Title]

| Attribute | Value |
|-----------|-------|
| **Accession** | [accession] |
| **Type** | RefSeq / GenBank |
| **Organism** | [scientific name] |
| **Strain** | [strain if applicable] |
| **Length** | [X,XXX bp / aa] |
| **Molecule** | DNA / mRNA / Protein |
| **Topology** | Linear / Circular |

**Curation Level**: ●●● RefSeq (curated) / ●●○ GenBank (submitted) / ●○○ Third-party

### Sequence Statistics
| Statistic | Value |
|-----------|-------|
| **Length** | [X,XXX] bp |
| **GC Content** | [XX.X]% |
| **Genes** | [N] (if genome) |
| **CDS** | [N] (if annotated) |

### Sequence Preview
```fasta
>[accession] [definition]
ATGCGATCGATCGATCGATCGATCGATCGATCGATCGATCGATCGATCGATCG
ATCGATCGATCGATCGATCGATCGATCGATCGATCGATCGATCGATCGATCGA
... [truncated, full sequence in download]

Annotations Summary (from GenBank format)

Alternative Sequences

Ranked by relevance and curation level:

Cross-Database References

Download Options

Formats Available

Direct Commands

# FASTA format
tu.tools.NCBI_get_sequence(
    operation="fetch_sequence",
    accession="[accession]",
    format="fasta"
)

# GenBank format (with annotations)
tu.tools.NCBI_get_sequence(
    operation="fetch_sequence",
    accession="[accession]",
    format="genbank"
)

Related Sequences

Other Strains/Isolates

Protein Products (if applicable)

Retrieved: [date] Database: NCBI Nucleotide

---

## Curation Level Tiers

| Tier | Symbol | Accession Prefix | Description |
|------|--------|------------------|-------------|
| RefSeq Reference | ●●●● | 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 |

Include in report:
```markdown
**Curation Level**: ●●●● RefSeq Reference
- Curated by NCBI RefSeq project
- Regular updates and validation
- Recommended for reference use

Completeness Checklist

Every sequence report MUST include:

Per Sequence (Required)

• Accession number
• Organism (scientific name)
• Sequence type (DNA/RNA/protein)
• Length
• Curation level
• Database source

Search Summary (Required)

• Query parameters
• Number of results
• Ranking rationale

Include Even If Limited

• Alternative sequences (or "Only one sequence found")
• Cross-database references (or "No cross-references available")
• Download instructions

Common Use Cases

Reference Genome

User: "Get E. coli K-12 complete genome"

result = tu.tools.NCBI_search_nucleotide(
    operation="search",
    organism="Escherichia coli",
    strain="K-12",
    seq_type="complete_genome",
    limit=3
)
# Return NC_000913.3 (RefSeq reference)

Gene Sequence

User: "Find human BRCA1 mRNA"

result = tu.tools.NCBI_search_nucleotide(
    operation="search",
    organism="Homo sapiens",
    gene="BRCA1",
    seq_type="mrna",
    limit=10
)

Specific Accession

User: "Get sequence for NC_045512.2" → Direct retrieval with full metadata

Strain Comparison

User: "Compare E. coli K-12 and O157:H7 genomes" → Search both strains, provide comparison table

Error Handling

Tool Reference

NCBI Tools (All Accessions)

ENA Tools (GenBank/EMBL Only)

Search Parameters Reference

NCBI_search_nucleotide

NCBI_get_sequence