tooluniverse-sequence-retrieval

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-submiss

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npx skills add mims-harvard/tooluniverse --skill tooluniverse-sequence-retrieval

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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: 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. 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: 1. Search Summary : query, database, result count 2. Primary Sequence : accession, type (RefSeq/GenBank), organism, strain, length, molecule, topology, curation level 3. Sequence Preview : first lines of FASTA (truncated) 4. Annotations Summary : CDS/tRNA/rRNA/regulatory feature counts (from GenBank format) 5. Alternative Sequences : ranked by relevance and curation, with ENA compatibility 6. Cross Database References : RefSeq, GenBank, ENA/EMBL, BioProject, BioSample 7. 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 1. What is the highest quality accession available? 2. Are there alternative accessions in other databases? 3. What is the annotation completeness? 4. Is the sequence from the expected organism/strain? 5. 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)