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. Prefix Type Use With NC_ RefSeq chromosome NCBI only NM_ RefSeq mRNA NCBI only NR_ RefSeq ncRNA NCBI only NP_ RefSeq protein NCBI only XM_ RefSeq predicted mRNA NCBI only U, M, K, X GenBank NCBI or ENA CP, NZ_* GenBank genome NCBI or ENA EMBL format EMBL ENA preferred 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

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

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

| 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) Feature Count Examples CDS [N] [gene names] tRNA [N] - rRNA [N] 16S, 23S Regulatory [N] promoters Alternative Sequences Ranked by relevance and curation level: Accession Type Length Description ENA Compatible NC_000913.3 RefSeq 4.6 Mb E. coli K-12 reference ✗ U00096.3 GenBank 4.6 Mb E. coli K-12 ✓ CP001509.3 GenBank 4.6 Mb E. coli DH10B ✓ Cross-Database References Database Accession Link RefSeq [NC_] [NCBI link] GenBank [U] [NCBI link] ENA/EMBL [same as GenBank] [ENA link] BioProject [PRJNA] [link] BioSample [SAMN] [link] Download Options Formats Available Format Description Use Case FASTA Sequence only BLAST, alignment GenBank Sequence + annotations Gene analysis GFF3 Annotations only Genome browsers 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 Accession Strain Similarity Notes [acc1] [strain1] 99.9% [notes] [acc2] [strain2] 99.5% [notes] Protein Products (if applicable) Protein Accession Product Name Length [NP_*] [protein name] [X] aa Retrieved: [date] Database: NCBI Nucleotide

Curation Level Tiers