{ "vercy": "1.0-draft", "publication": { "status": "research-draft", "adjudicationStatus": "unreviewed", "publishableCanonical": false, "generatedAt": "2026-09-12T10:07:49Z", "providers": [ "Codex" ], "breadth": "recalled by Codex without web access - no source was read", "missingProviders": [], "pass": 2, "cost": { "grok": { "seconds": 22.7, "error": "Reading additional input from stdin...\nOpenAI Codex v0.153.4\n--------\nworkdir: R:\\02_PROJECTS\\02_Meta_Models_Platforms\\Ver.cy\\current\\thing-registry-backlog\nmodel: gpt-6-astra\nprovider: openai\napproval: never\nsandbox: read-only\nreasoning effort: none\nreasoning summaries: none\nsession id: 01a09515-579e-7221-afe1-5fd3ed52b851\n--------\nuser\nDescribe what is already known about one registered thing. Answer as JSON only, no prose around it.\n\nThing: guide RNA\nSense to describe: (none recorded)\nDomain code: PHY.MAT\nAlso known as: (none)\n\n\nContext for this batch of 1001 things:\n# Batch 043: 1001 regis", "usd": 0.0, "recall": true }, "codex": { "seconds": 71.5, "error": "Reading additional input from stdin...\nOpenAI Codex v0.153.4\n--------\nworkdir: R:\\02_PROJECTS\\02_Meta_Models_Platforms\\Ver.cy\\current\\thing-registry-backlog\nmodel: gpt-6-astra\nprovider: openai\napproval: never\nsandbox: read-only\nreasoning effort: none\nreasoning summaries: none\nsession id: 01a09515-57a6-7d40-a9c5-31f93397b99c\n--------\nuser\nYou are drafting a Vercy meta-model for one registered thing. Answer as JSON only, no prose around it.\n\nThing: guide RNA\nRegistry id: vr.tr.guide-rna\nPlane / domain: PHY / PHY.MAT\nRegistry definition: (none recorded)\nNames folded into this entry: (none)\n\n\nCont" } }, "enrichment": { "pass": 3, "engine": "codex", "producedAt": "2026-10-08T12:00:00Z", "ingestedAt": "2026-10-08T18:55:14+00:00", "fields": [ "agent_conduct", "ethics", "owners", "visual_identification" ] }, "gate": { "passed": true, "version": "1.0", "at": "2026-10-08T18:56:48+00:00", "evidence": [ "completeness 1.00", "sense: Wikidata description", "2 live sources", "review by codex: pass" ] } }, "metaModel": { "id": "THING-Q4039747", "registryId": "vr.tr.guide-rna", "name": "guide RNA", "version": "0.1.0-research.1", "entryKind": "thing", "family": "Thing Registry", "domain": [ "PHY.MAT" ], "status": "research-draft" }, "canonicalUrl": "https://ver.cy/models/thing/q4039747/", "model": { "registry_id": "vr.tr.guide-rna", "name": "guide RNA", "purpose": "Enable an agent to identify a guide RNA, assess its molecular condition and targeting evidence, and determine its suitability for a specified compatible biological system.", "definition": "A guide RNA is an RNA molecule whose sequence directs a molecular complex to a complementary nucleic-acid target, including RNAs used in CRISPR targeting and mitochondrial RNA editing.", "scope_statement": "This model owns the guide RNA molecular entity registered as vr.tr.guide-rna in PHY / PHY.MAT, including sequence-defined variants and physical preparations; because the registry supplies no definition, its provisional scope includes CRISPR guides and RNA-editing guides with their mechanisms explicitly distinguished.", "in_scope": [ "Guide RNA sequence, molecular architecture, chemical modifications and maturation state", "Target recognition regions and their relationship to an identified DNA or RNA substrate", "Compatibility with a specified effector and any required companion RNA", "Physical preparation, concentration, integrity, purity and storage history", "Evidence for guide-dependent activity, specificity and application suitability" ], "out_of_scope": [ "Effector proteins and editing complexes as independently modelled entities", "DNA constructs, vectors and transcription systems that encode a guide RNA", "Delivery vehicles and complete formulated products", "Target organisms, cells, genomes and transcripts beyond their targeting relationships", "Complete editing workflows, downstream repair pathways and resulting engineered organisms" ], "distinguishing_features": [ "A guide RNA supplies sequence-dependent recognition of a nucleic-acid substrate within a specified functional system; being a short RNA alone does not establish guide identity.", "The RNA molecule is distinct from a DNA construct encoding it, even when both are informally labelled with the same guide name.", "For Cas9, an engineered single-guide RNA combines guide and companion-RNA functions in one chain, whereas a dual-RNA guide uses separate crRNA and tracrRNA components.", "A spacer sequence alone does not identify the complete guide: scaffold, companion requirements, termini and modifications can distinguish functionally different molecules.", "The name does not uniquely imply CRISPR: RNA-editing guides require a separate mechanism classification, and antisense or RNA-interference reagents should not be merged solely because they base-pair with a target." ], "characteristics": [ { "name": "Guide mechanism", "kind": "category", "unit_or_values": "CRISPR-associated targeting; RNA-editing guidance; other evidenced mechanism; unresolved", "why_it_matters": "Determines which structural, targeting and compatibility questions apply." }, { "name": "Complete molecular sequence", "kind": "category", "unit_or_values": "5′-to-3′ sequence for every RNA chain, with annotated regions and explicit ambiguity", "why_it_matters": "Distinguishes the physical molecular identity from a guide nickname or target label." }, { "name": "Chain and recognition-region length", "kind": "measurement", "unit_or_values": "nucleotides per chain and per annotated recognition region", "why_it_matters": "Supports architecture checks without assuming one universal guide length." }, { "name": "Chemical constitution", "kind": "category", "unit_or_values": "Position-specific base, sugar and backbone modifications; terminal chemistry", "why_it_matters": "Sequence-identical guides can differ in stability, recognition and effector compatibility." }, { "name": "Target relationship", "kind": "relation", "unit_or_values": "Reference accession and version, substrate type, sequence, coordinates, strand and alignment", "why_it_matters": "Makes the intended recognition relationship reproducible and exposes reference mismatches." }, { "name": "Effector and companion compatibility", "kind": "relation", "unit_or_values": "Named effector variant, scaffold version and required companion RNA, with evidence status", "why_it_matters": "Complementarity alone does not establish that a guide can function in the proposed system." }, { "name": "Maturation and association state", "kind": "state", "unit_or_values": "Precursor or mature; free, companion-paired, effector-bound or unknown", "why_it_matters": "Separates available material from the functional form required for use." }, { "name": "Preparation concentration", "kind": "measurement", "unit_or_values": "mol/L or mass/volume, with molecular-weight basis, method and uncertainty", "why_it_matters": "Supports amount comparisons and identifies assumptions in concentration conversions." }, { "name": "Intact guide fraction", "kind": "measurement", "unit_or_values": "Percentage, with assay, denominator and measurement date", "why_it_matters": "Distinguishes total measured RNA from intact intended guide material." }, { "name": "Context-specific functional response", "kind": "measurement", "unit_or_values": "Endpoint-specific units or percentage, with controls, biological context and uncertainty", "why_it_matters": "Prevents activity in one assay from becoming an unconditional property of the guide." } ], "affordances": [ "Resolve whether two guide records describe the same molecule, a sequence variant or different preparations.", "Check whether guide architecture and companion requirements match a named effector.", "Map an annotated recognition region to a versioned target and flag ambiguous or incompatible matches.", "Compare predicted specificity with experimentally observed target and non-target responses.", "Assess preparation suitability against explicit integrity, purity and storage requirements.", "Select, defer or reject a guide for a stated application while preserving the supporting evidence and unresolved conditions." ], "what_it_is_for": [ "Guide RNAs occur in biological systems where sequence complementarity helps direct molecular complexes to nucleic acid targets.", "Research uses designed guide RNAs to direct compatible CRISPR complexes for targeting, editing or regulation.", "Some mitochondrial RNA editing systems use guide RNAs to specify changes to RNA transcripts." ], "standards_and_regulation": [ "The Abbreviations and Symbols for Nucleic Acids, Polynucleotides, and Their Constituents recommendations issued jointly by the International Union of Pure and Applied Chemistry and the International Union of Biochemistry apply to guide RNA sequence notation." ], "failure_modes_and_hazards": [ "Unintended targeting can alter or regulate nucleic acids beyond the intended target.", "Degradation, contamination or incorrect sequence identity can cause failed experiments and misleading conclusions.", "Incompatible guide RNA and molecular complex combinations can produce ineffective or unexpected activity.", "Biological delivery can provoke unwanted cellular responses that depend on the material and receiving system." ], "facets_not_applicable": { "recognition": "Guide RNA identity cannot be established by visual appearance and requires molecular analysis and functional context." }, "agent_conduct": { "may": [ "Explain how guide RNAs direct molecular complexes through sequence complementarity.", "Distinguish guide RNAs involved in CRISPR targeting from those involved in mitochondrial RNA editing." ], "must_not": [ "Claim that sequence complementarity guarantees exclusive targeting or a particular biological outcome.", "Treat every guide RNA as a component of a genome editing system.", "Assist in using guide RNAs to cause harmful genetic changes or other biological harm." ], "requires_human": [ "The responsible investigator and relevant ethics authority must decide whether a proposed guide RNA application is acceptable." ] }, "ethics": { "considerations": [ "Overstated targeting precision can obscure unintended effects and weaken informed consent.", "Applications with potentially heritable consequences raise responsibilities toward people who cannot consent." ], "affected_parties": [ "Research participants or patients affected by guide RNA applications.", "Future generations or ecosystems affected by persistent biological changes." ] }, "owners": { "steward": "The custodian responsible for the guide RNA record and its intended application.", "master_systems": [ "Public nucleotide sequence archives where the guide RNA sequence has been deposited." ] }, "visual_identification": [ "A documented molecular diagram identifies the guide RNA strand and its complementary nucleic acid target.", "Annotations identifying the associated molecular complex distinguish the guide RNA's biological context.", "Neither a sample's visible appearance nor an unannotated RNA shape establishes guide RNA identity." ] }, "sources": [ { "id": "wikidata", "title": "Wikidata item Q4039747: guide RNA", "url": "https://www.wikidata.org/wiki/Q4039747", "url_status": "live", "what_it_supports": "identity and sense of the item", "checked_by": "wikidata-api" }, { "id": "wikipedia-en", "title": "Wikipedia: Guide RNA", "url": "https://en.wikipedia.org/wiki/Guide_RNA", "url_status": "live", "what_it_supports": "general description of the item", "checked_by": "wikidata-api sitelink" } ], "structure": { "bundles": [ { "id": "guide-identity-and-mechanism", "name": "Guide identity and mechanism", "description": "Establish which molecular entity and biological meaning the guide designation refers to.", "rationale": "Guide RNA is a functional class, so neither a generic chemical identifier nor an assumed CRISPR interpretation adequately establishes identity.", "layers": [ { "id": "mechanistic-classification", "name": "Mechanistic classification", "description": "Distinguish guide systems before applying system-specific requirements.", "findings": [ { "id": "guide-role", "name": "Guide role", "description": "Record the process in which the RNA provides recognition or editing information. RNA-editing guidance is an evidenced use of the term: [Structural basis of the RNA-editing cascade in trypanosome mitochondria](https://www.nature.com/articles/s41586-026-10831-x).", "questions": [ { "text": "Which biological mechanism makes this RNA a guide, and what evidence establishes that role?", "kind": "definition", "id": "guide-role-q01" }, { "text": "Does this record denote the RNA itself, an encoding construct, or a larger guide-containing complex?", "kind": "boundary", "id": "guide-role-q02" } ] } ] }, { "id": "molecular-identity", "name": "Molecular identity", "description": "Resolve guide names into sequence-defined molecular variants.", "findings": [ { "id": "sequence-and-variant-record", "name": "Sequence and variant record", "description": "Identify every chain, its annotated regions, terminal chemistry and modifications independently of target-based nicknames.", "questions": [ { "text": "What complete sequences, chain boundaries, termini and chemical modifications define this guide variant?", "kind": "definition", "id": "sequence-and-variant-record-q01" }, { "text": "Which accession, design version or supplier record establishes that identity, and was it independently verified?", "kind": "provenance", "id": "sequence-and-variant-record-q02" } ] } ] } ] }, { "id": "target-recognition", "name": "Target recognition", "description": "Describe the intended substrate and the sequence relationship through which the guide recognizes it.", "rationale": "A guide cannot be judged by its sequence without the target reference, orientation and mechanism-dependent recognition constraints.", "layers": [ { "id": "target-reference", "name": "Target reference", "description": "Anchor recognition to a defined DNA or RNA sequence.", "findings": [ { "id": "target-alignment", "name": "Target alignment", "description": "Preserve target identity, version, strand and guide-to-target pairing rather than recording only a gene name.", "questions": [ { "text": "Which substrate sequence, reference version, coordinates and strand define the intended target?", "kind": "definition", "id": "target-alignment-q01" }, { "text": "How does the recognition region align to that substrate, including mismatches, gaps and relevant sample variants?", "kind": "measurement", "id": "target-alignment-q02" } ] } ] }, { "id": "recognition-constraints", "name": "Recognition constraints", "description": "Capture requirements imposed by the particular guide-effector mechanism.", "findings": [ { "id": "recognition-eligibility", "name": "Recognition eligibility", "description": "Treat adjacent motifs, substrate accessibility and pairing requirements as system-dependent conditions; do not assume a universal PAM requirement.", "questions": [ { "text": "Which adjacent-sequence, pairing or substrate-state requirements apply to this exact guide-effector system?", "kind": "definition", "id": "recognition-eligibility-q01" }, { "text": "What evidence supports target accessibility in the intended biological context?", "kind": "provenance", "id": "recognition-eligibility-q02" } ] } ] } ] }, { "id": "architecture-and-effector-compatibility", "name": "Architecture and effector compatibility", "description": "Determine whether the guide has the structural components required by its functional partners.", "rationale": "A target-complementary RNA may remain unusable if its scaffold, companion RNA or processing state is incompatible.", "layers": [ { "id": "guide-architecture", "name": "Guide architecture", "description": "Separate target-recognition regions from structural and companion-binding regions.", "findings": [ { "id": "chain-and-scaffold-arrangement", "name": "Chain and scaffold arrangement", "description": "Record single-chain or multipart architecture and scaffold identity. Cas9 guide format and folding distinctions are supported by [Improved gRNA secondary structures allow editing of target sites resistant to CRISPR-Cas9 cleavage](https://www.nature.com/articles/s41467-022-28137-7).", "questions": [ { "text": "Which regions provide target recognition, partner binding and any additional guide function?", "kind": "definition", "id": "chain-and-scaffold-arrangement-q01" }, { "text": "What evidence shows that the proposed chain arrangement and scaffold form a functional guide in this system?", "kind": "provenance", "id": "chain-and-scaffold-arrangement-q02" } ] } ] }, { "id": "functional-partners", "name": "Functional partners", "description": "Identify the effector, companion RNAs and maturation dependencies.", "findings": [ { "id": "assembly-readiness", "name": "Assembly readiness", "description": "Distinguish predicted compatibility from demonstrated partner association and activity.", "questions": [ { "text": "Which effector variant, companion RNA and processing steps are required for this guide to function?", "kind": "definition", "id": "assembly-readiness-q01" }, { "text": "Is the available RNA in the required mature and associated state, and what evidence supports proceeding with its intended use?", "kind": "action", "id": "assembly-readiness-q02" } ] } ] } ] }, { "id": "rna-preparation-and-condition", "name": "RNA preparation and condition", "description": "Describe the actual material carrying a guide identity and its changing condition.", "rationale": "A correct design does not establish that a particular RNA preparation is intact, sufficiently pure or suitable for use.", "layers": [ { "id": "production-and-composition", "name": "Production and composition", "description": "Connect synthesis or isolation history with measured preparation contents.", "findings": [ { "id": "preparation-quality", "name": "Preparation quality", "description": "Record production route, lot identity, concentration basis and assays distinguishing intended guide from truncated RNA and other relevant impurities.", "questions": [ { "text": "How was this preparation produced and purified, and which lot-specific records connect it to the intended molecular identity?", "kind": "provenance", "id": "preparation-quality-q01" }, { "text": "What concentration, intact fraction and relevant impurity measurements are available, with methods and detection limits?", "kind": "measurement", "id": "preparation-quality-q02" } ] } ] }, { "id": "stability-and-handling", "name": "Stability and handling", "description": "Track conditions that affect RNA integrity and application suitability.", "findings": [ { "id": "condition-dependent-usability", "name": "Condition-dependent usability", "description": "Associate buffer, storage duration, temperature excursions and handling history with preparation-specific stability evidence.", "questions": [ { "text": "What buffer, temperature, elapsed storage time and handling events characterize the material now?", "kind": "measurement", "id": "condition-dependent-usability-q01" }, { "text": "Which guide-specific acceptance criteria determine whether this preparation can be used, needs reassessment or should be rejected?", "kind": "action", "id": "condition-dependent-usability-q02" } ] } ] } ] }, { "id": "functional-evidence-and-use-decisions", "name": "Functional evidence and use decisions", "description": "Connect guide activity and specificity evidence to a bounded intended application.", "rationale": "Binding, cleavage, editing and regulation are different outcomes, and neither predicted activity nor a single successful assay establishes universal suitability.", "layers": [ { "id": "intended-response", "name": "Intended response", "description": "Identify the endpoint the guide-containing system is expected to produce.", "findings": [ { "id": "guide-dependent-performance", "name": "Guide-dependent performance", "description": "Record measured responses with controls and conditions while keeping guide contribution distinct from effector, delivery and downstream biology.", "questions": [ { "text": "Is the intended endpoint binding, cleavage, RNA editing, DNA editing, regulation or another specified response?", "kind": "definition", "id": "guide-dependent-performance-q01" }, { "text": "What controlled measurements support that endpoint, and in which effector, delivery and biological context were they obtained?", "kind": "measurement", "id": "guide-dependent-performance-q02" } ] } ] }, { "id": "specificity-and-applicability", "name": "Specificity and applicability", "description": "Assess alternative target interactions and limits on transferring results to a new use.", "findings": [ { "id": "specificity-evidence", "name": "Specificity evidence", "description": "Separate computational candidates, observed non-target responses and unexamined possibilities, including assay coverage and uncertainty.", "questions": [ { "text": "Which unintended interactions or outcomes are predicted or observed, and what reference coverage and detection limits constrain those conclusions?", "kind": "measurement", "id": "specificity-evidence-q01" }, { "text": "Does the available evidence meet the intended application's activity and specificity criteria, or what additional evidence is required?", "kind": "action", "id": "specificity-evidence-q02" } ] } ] } ] }, { "id": "evidence-and-external-alignment", "name": "Evidence and external alignment", "description": "What the world already says about this thing, gathered so the model can be checked against it.", "rationale": "A model that cannot be lined up against existing standards, identifiers and practice cannot be adopted by anyone who already uses them.", "layers": [ { "id": "reported-evidence", "name": "Reported evidence", "description": "Findings from the breadth pass, kept separate from the structural claims.", "findings": [ { "id": "evidence-confidence-notes", "name": "Check these first", "description": "Recalled without web access and unsourced; every item is a lead to verify.", "evidence": [ "No sense is recorded: establish whether the registry means CRISPR guides, mitochondrial editing guides or the broader functional category.", "This is a sequence-dependent class of molecules, not one chemically uniform substance with universal physical constants or a single CAS identity.", "Length examples apply specifically to conventional SpCas9 designs; other CRISPR systems and mitochondrial guides differ." ], "questions": [ { "id": "evidence-confidence-notes-q01", "text": "Which of these check these first hold for the sense of guide RNA this model covers, and on what evidence?", "kind": "provenance" } ] }, { "id": "evidence-kinds", "name": "Kinds and varieties", "description": "Recalled without web access and unsourced; every item is a lead to verify.", "evidence": [ "CRISPR RNA (crRNA)", "Engineered CRISPR single-guide RNA (sgRNA)", "Guide RNA for kinetoplastid mitochondrial RNA editing" ], "questions": [ { "id": "evidence-kinds-q01", "text": "Which of these kinds and varieties hold for the sense of guide RNA this model covers, and on what evidence?", "kind": "provenance" } ] }, { "id": "evidence-identifiers", "name": "Identifiers and schemes", "description": "Recalled without web access and unsourced; every item is a lead to verify.", "evidence": [ { "scheme": "INSDC sequence accession", "value_or_pattern": "Accession with sequence-version suffix", "note": "A deposited sequence may have an accession in GenBank, ENA or DDBJ; the term guide RNA has no single sequence identifier." } ], "questions": [ { "id": "evidence-identifiers-q01", "text": "Which of these identifiers and schemes hold for the sense of guide RNA this model covers, and on what evidence?", "kind": "provenance" } ] }, { "id": "evidence-real-world-use", "name": "Real-world use", "description": "Recalled without web access and unsourced; every item is a lead to verify.", "evidence": [ "Directing CRISPR nucleases to selected DNA or RNA targets.", "Targeting CRISPR base editors and prime editors to genomic sites.", "Directing catalytically inactive CRISPR proteins for gene regulation or locus imaging.", "Providing sequence information for uridine insertion and deletion during kinetoplastid mitochondrial RNA editing." ], "questions": [ { "id": "evidence-real-world-use-q01", "text": "Which of these real-world use hold for the sense of guide RNA this model covers, and on what evidence?", "kind": "provenance" } ] }, { "id": "evidence-measurements", "name": "Typical measurements", "description": "Recalled without web access and unsourced; every item is a lead to verify.", "evidence": [ { "quantity": "Target-complementary spacer length in commonly used SpCas9 guides", "typical_range": "Typically 20", "unit": "nucleotides" }, { "quantity": "Total length of a conventional engineered SpCas9 sgRNA", "typical_range": "Approximately 100; scaffold design can change this", "unit": "nucleotides" } ], "questions": [ { "id": "evidence-measurements-q01", "text": "Which of these typical measurements hold for the sense of guide RNA this model covers, and on what evidence?", "kind": "provenance" } ] }, { "id": "evidence-failure-modes-and-hazards", "name": "Failure modes and hazards", "description": "Recalled without web access and unsourced; every item is a lead to verify.", "evidence": [ "Partial complementarity can permit unintended targeting; consequences depend on the associated effector.", "An incompatible scaffold, unsuitable target context or inaccessible target can prevent productive activity.", "RNase degradation and poor delivery can reduce the amount of functional guide RNA.", "Guide sequence, structure, chemical modifications and impurities can influence innate immune activation in experimental or therapeutic delivery.", "Successful targeting by a nuclease complex can still produce unwanted repair outcomes, including large deletions or rearrangements." ], "questions": [ { "id": "evidence-failure-modes-and-hazards-q01", "text": "Which of these failure modes and hazards hold for the sense of guide RNA this model covers, and on what evidence?", "kind": "provenance" } ] }, { "id": "evidence-neighbours", "name": "Neighbouring kinds and how to tell them apart", "description": "Recalled without web access and unsourced; every item is a lead to verify.", "evidence": [ { "name": "RNA", "difference": "RNA is the broader molecular class; guide RNA is distinguished by its targeting or sequence-guidance function." }, { "name": "Single-guide RNA", "difference": "An sgRNA is an engineered CRISPR guide architecture, commonly combining crRNA and tracrRNA functions; guide RNA is the broader term." }, { "name": "Trans-activating CRISPR RNA (tracrRNA)", "difference": "In natural Cas9 systems, tracrRNA pairs with crRNA and supports complex function; the target-complementary sequence is carried by crRNA." }, { "name": "Cas protein", "difference": "A Cas protein is a protein component of a CRISPR system; the guide RNA supplies RNA-based targeting information." }, { "name": "Small interfering RNA", "difference": "An siRNA guides an Argonaute-containing RNA-silencing complex and is generally classified by that pathway rather than as a CRISPR guide." } ], "questions": [ { "id": "evidence-neighbours-q01", "text": "Which of these neighbouring kinds and how to tell them apart hold for the sense of guide RNA this model covers, and on what evidence?", "kind": "provenance" } ] } ] } ] } ] }, "openQuestions": [ "Does the underlying registry concept mean guide RNA broadly, specifically CRISPR guide RNA, or specifically RNA-editing guide RNA?", "Does an existing Vercy RNA or CRISPR world model already own this concept, requiring a link rather than a separate publication?", "Which additional guide mechanisms, if any, belong within this registry entry rather than neighbouring RNA categories?", "Which mechanism-specific architecture and target-recognition constraints have sufficient primary evidence to become model requirements?", "Which preparation quality, stability and specificity acceptance criteria are justified for each intended use, given that no universal thresholds have been established here?" ], "statistics": { "bundles": 6, "layers": 11, "findings": 17, "questions": 27 } }