{ "vercy": "1.0-draft", "publication": { "status": "research-draft", "adjudicationStatus": "unreviewed", "publishableCanonical": false, "generatedAt": "2026-09-12T11:25:53Z", "providers": [ "Codex" ], "breadth": "recalled by Codex without web access - no source was read", "missingProviders": [], "pass": 2, "cost": { "grok": { "seconds": 18.0, "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: 01a0955c-ba48-7763-97fd-59561e8f3483\n--------\nuser\nDescribe what is already known about one registered thing. Answer as JSON only, no prose around it.\n\nThing: MSH2\nSense to describe: (none recorded)\nDomain code: PHY.OBJ\nAlso known as: (none)\n\n\nContext for this batch of 1001 things:\n# Batch 044: 1001 registered", "usd": 0.0, "recall": true }, "codex": { "seconds": 76.1, "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: 01a0955c-ba48-7572-b730-d930b3351643\n--------\nuser\nYou are drafting a Vercy meta-model for one registered thing. Answer as JSON only, no prose around it.\n\nThing: MSH2\nRegistry id: vr.tr.msh2\nPlane / domain: PHY / PHY.OBJ\nRegistry definition: (none recorded)\nNames folded into this entry: (none)\n\n\nContext for th" } }, "enrichment": { "pass": 3, "engine": "claude", "producedAt": "2026-10-06T12:00:00Z", "ingestedAt": "2026-10-06T08:57:13+00:00", "fields": [ "agent_conduct", "ethics", "failure_modes_and_hazards", "owners", "standards_and_regulation", "visual_identification" ] }, "gate": { "passed": true, "version": "1.0", "at": "2026-10-07T10:10:26+00:00", "evidence": [ "completeness 1.00", "sense: Wikidata description", "2 live sources", "review by codex: pass" ] } }, "metaModel": { "id": "THING-Q14911688", "registryId": "vr.tr.msh2", "name": "MSH2", "version": "0.1.0-research.1", "entryKind": "thing", "family": "Thing Registry", "domain": [ "PHY.OBJ" ], "status": "research-draft" }, "canonicalUrl": "https://ver.cy/models/thing/q14911688/", "model": { "registry_id": "vr.tr.msh2", "name": "MSH2", "purpose": "Enable an agent to identify MSH2, distinguish its gene and protein referents, and assess evidence about its molecular state and contribution to DNA mismatch repair.", "definition": "MSH2 is a human protein-coding gene whose product recognizes DNA replication errors in complexes with MSH6 or MSH3 and initiates DNA mismatch repair.", "scope_statement": "This draft provisionally treats vr.tr.msh2 as human MSH2, owning its molecular identity, gene-to-product relationships, repair-complex participation and experimentally supported functional states; the registry must still confirm species and whether the primary referent is the gene or protein.", "in_scope": [ "Species-qualified MSH2 identity and reference accessions", "Relationships among the MSH2 locus, transcripts, protein isoforms and observed variants", "MSH2 participation in MSH6-containing and MSH3-containing complexes", "DNA-substrate recognition and nucleotide-dependent functional states", "MSH2-specific expression, localization and functional-assay evidence" ], "out_of_scope": [ "Independent models of MSH3, MSH6 and downstream repair proteins", "The complete DNA mismatch-repair pathway", "Individual patients, pedigrees and tumour specimens", "Diagnosis, surveillance and treatment of hereditary cancer syndromes", "Laboratory instruments, reagent inventories and generic assay procedures" ], "distinguishing_features": [ "Resolve the symbol against a species-qualified accession: human MSH2 is represented by NCBI Gene 4436, whereas a protein requires a protein accession. [NCBI Gene](https://www.ncbi.nlm.nih.gov/gene/4436/)", "Distinguish MSH2 from its binding partners: human MSH2 forms complexes with MSH3 or MSH6, so identification of a partner alone does not identify MSH2. [Primary study](https://pmc.ncbi.nlm.nih.gov/articles/PMC19374/)", "Distinguish the MSH2 subunit from the complete MSH2-MSH6 or MSH2-MSH3 complex by recording the experimentally identified constituents.", "Require a sequence and reference mapping to distinguish an MSH2 variant or engineered construct from the reference product and from other MutS-family proteins.", "Treat MSH2 abundance, mismatch binding and successful repair as separate observations; one measurement does not establish all three." ], "characteristics": [ { "name": "Molecular referent", "kind": "category", "unit_or_values": "gene locus | transcript | protein | engineered construct", "why_it_matters": "Prevents a DNA variant, RNA measurement and protein observation from being treated as interchangeable." }, { "name": "Species and reference identity", "kind": "relation", "unit_or_values": "taxon identifier plus versioned gene, transcript or protein accession", "why_it_matters": "Anchors MSH2 identity and limits transfer of evidence between organisms." }, { "name": "Sequence alteration", "kind": "relation", "unit_or_values": "reference-qualified DNA, RNA or protein change; endogenous or engineered origin", "why_it_matters": "Makes variant comparisons reproducible and separates natural alleles from experimental constructs." }, { "name": "Complex membership", "kind": "state", "unit_or_values": "MSH6-associated | MSH3-associated | unbound | other observed association | unresolved", "why_it_matters": "Identifies the molecular assembly to which a substrate-binding or repair result applies." }, { "name": "Nucleotide condition", "kind": "state", "unit_or_values": "ATP-bound | ADP-bound | nucleotide-free | mixed | unmeasured", "why_it_matters": "Supports interpretation of nucleotide-dependent binding and conformational experiments." }, { "name": "DNA substrate", "kind": "category", "unit_or_values": "matched duplex | specified base mismatch | insertion/deletion loop with size in nucleotides", "why_it_matters": "Prevents generalizing activity measured on one substrate to every replication error." }, { "name": "MSH2 abundance", "kind": "measurement", "unit_or_values": "assay-specific concentration or normalized abundance, with denominator and detection limit", "why_it_matters": "Separates protein availability from intrinsic activity and technical non-detection." }, { "name": "Subcellular distribution", "kind": "state", "unit_or_values": "observed compartment, cell type, method and sampling condition", "why_it_matters": "Places an MSH2 observation in the cellular context where function is being assessed." }, { "name": "Repair-related activity", "kind": "measurement", "unit_or_values": "binding affinity in mol/L, ATP turnover in s^-1, or repair fraction relative to specified controls", "why_it_matters": "Preserves the distinction between molecular activities and integrated repair outcomes." } ], "affordances": [ "Resolve an MSH2-labelled record to a species and molecular reference.", "Map an observed sequence alteration to the relevant transcript and protein product.", "Compare MSH2 observations only after aligning partner, substrate and assay conditions.", "Identify which measurement could distinguish reduced abundance from impaired complex formation or activity.", "Link a functional interpretation to its experimental evidence and record conflicting results." ], "agent_conduct": { "may": [ "Describe MSH2 and its role in DNA mismatch repair, citing sources.", "Explain in general terms that inherited variants can raise cancer risk and that genetic counselling is available." ], "must_not": [ "Tell a person they have a hereditary cancer syndrome from a variant without clinical review.", "Share a person's genetic result with relatives, employers or insurers without consent.", "Classify a variant of uncertain significance as harmful or harmless without evidence.", "Recommend screening or surgery for a person." ], "requires_human": [ "Returning genetic results to a person or family.", "Any decision on screening or preventive surgery." ] }, "ethics": { "considerations": [ "Hereditary cancer results affect whole families and can lead to discrimination.", "People have a right to decide whether to learn their genetic risk." ], "affected_parties": [ "People with tested variants", "Relatives", "Clinicians and counsellors" ] }, "owners": { "steward": "The person whose genome carries it; laboratories and clinical variant databases hold records.", "master_systems": [ "Clinical variant databases", "Gene and variant databases" ] }, "visual_identification": [ "Not visible; known from sequence data or tumour staining for the protein.", "Loss of protein staining in tumour tissue is reported by pathologists." ], "failure_modes_and_hazards": [ "Misclassification of variants.", "Genetic discrimination after disclosure." ], "standards_and_regulation": [ "Human gene nomenclature, HUGO Gene Nomenclature Committee (HGNC), which approves the gene symbol." ], "what_it_is_for": [ "The human MSH2 gene is encountered in studies of DNA mismatch repair, genome stability and inherited cancer susceptibility.", "Its sequence and expression are examined to investigate repair defects, with findings about the gene distinguished from measurements of its encoded protein." ] }, "sources": [ { "id": "wikidata", "title": "Wikidata item Q14911688: MSH2", "url": "https://www.wikidata.org/wiki/Q14911688", "url_status": "live", "what_it_supports": "identity and sense of the item", "checked_by": "wikidata-api" }, { "id": "wikipedia-en", "title": "Wikipedia: MSH2", "url": "https://en.wikipedia.org/wiki/MSH2", "url_status": "live", "what_it_supports": "general description of the item", "checked_by": "wikidata-api sitelink" } ], "structure": { "bundles": [ { "id": "msh2-reference-identity", "name": "MSH2 reference identity", "description": "Establish what molecular entity the registry name denotes.", "rationale": "MSH2 names both a gene and its product, while the supplied registry record establishes neither species nor molecular level.", "layers": [ { "id": "species-and-referent", "name": "Species and referent", "description": "Resolve organism and gene-versus-protein identity before attaching biological claims.", "findings": [ { "id": "human-reference-anchor", "name": "Human reference anchor", "description": "NCBI identifies human MSH2 as a protein-coding gene with Gene ID 4436; this supports the provisional human interpretation but does not establish the registry's intended referent. [NCBI Gene](https://www.ncbi.nlm.nih.gov/gene/4436/)", "questions": [ { "text": "Does the registry's originating record identify human MSH2, an ortholog or a cross-species concept?", "kind": "provenance", "id": "human-reference-anchor-q01" }, { "text": "Does vr.tr.msh2 primarily denote the gene locus or the encoded protein?", "kind": "boundary", "id": "human-reference-anchor-q02" } ] } ] }, { "id": "sequence-and-product-mapping", "name": "Sequence and product mapping", "description": "Connect each molecular observation to an explicit reference.", "findings": [ { "id": "reference-qualified-products", "name": "Reference-qualified products", "description": "Record transcript, protein and construct references separately, including sequence versions and any engineered changes.", "questions": [ { "text": "Which versioned transcript and protein accessions define the MSH2 product under examination?", "kind": "definition", "id": "reference-qualified-products-q01" }, { "text": "Does the observed material contain a splice difference, truncation, tag or substitution relative to that reference?", "kind": "measurement", "id": "reference-qualified-products-q02" } ] } ] } ] }, { "id": "msh2-repair-assemblies", "name": "MSH2 repair assemblies", "description": "Describe MSH2 through its experimentally supported partner and substrate relationships.", "rationale": "A result for an MSH2-containing heterodimer cannot automatically be attributed to isolated MSH2 or its alternative complex.", "layers": [ { "id": "partner-defined-complexes", "name": "Partner-defined complexes", "description": "Identify the assembly present in each functional observation.", "findings": [ { "id": "msh3-and-msh6-partnerships", "name": "MSH3 and MSH6 partnerships", "description": "Human MSH2 forms specific mispair-binding complexes with MSH3 and MSH6; record the partner as part of the experimental context. [Primary study](https://pmc.ncbi.nlm.nih.gov/articles/PMC19374/)", "questions": [ { "text": "Was MSH2 measured alone, with MSH6 or with MSH3?", "kind": "definition", "id": "msh3-and-msh6-partnerships-q01" }, { "text": "What evidence establishes association rather than merely detecting both proteins in the same sample?", "kind": "provenance", "id": "msh3-and-msh6-partnerships-q02" } ] } ] }, { "id": "substrate-resolved-recognition", "name": "Substrate-resolved recognition", "description": "Attach binding observations to the exact DNA substrate and complex.", "findings": [ { "id": "mismatch-specific-readouts", "name": "Mismatch-specific readouts", "description": "Represent DNA recognition using mismatch identity, loop size, sequence context and a matched-duplex comparison.", "questions": [ { "text": "Which base mismatch or insertion/deletion loop was tested, and in what DNA sequence context?", "kind": "definition", "id": "mismatch-specific-readouts-q01" }, { "text": "How did binding compare with matched DNA under the same protein and buffer conditions?", "kind": "measurement", "id": "mismatch-specific-readouts-q02" } ] } ] } ] }, { "id": "msh2-functional-state", "name": "MSH2 functional state", "description": "Separate nucleotide-dependent molecular behaviour from cellular availability.", "rationale": "An agent needs to distinguish an activity defect from absent protein, altered location or an unsuitable assay state.", "layers": [ { "id": "nucleotide-coupled-behaviour", "name": "Nucleotide-coupled behaviour", "description": "Record nucleotide conditions and the molecular transition actually observed.", "findings": [ { "id": "binding-hydrolysis-and-clamping", "name": "Binding, hydrolysis and clamping", "description": "Experiments on human MSH2-MSH6 support ATP-bound sliding-clamp behaviour; ATP binding, hydrolysis and clamp formation require distinct evidence. [Primary study](https://pubmed.ncbi.nlm.nih.gov/10078208/)", "questions": [ { "text": "Which nucleotides, concentrations and cofactors were present during the MSH2-complex assay?", "kind": "measurement", "id": "binding-hydrolysis-and-clamping-q01" }, { "text": "Does the readout establish nucleotide binding, ATP turnover, DNA retention or sliding-clamp formation?", "kind": "boundary", "id": "binding-hydrolysis-and-clamping-q02" } ] } ] }, { "id": "cellular-availability", "name": "Cellular availability", "description": "Locate and quantify the relevant MSH2 product in its biological context.", "findings": [ { "id": "expression-and-localization-evidence", "name": "Expression and localization evidence", "description": "Keep RNA expression, protein abundance and subcellular distribution separate, with cell type and detection controls.", "questions": [ { "text": "Was MSH2 RNA or protein measured, in which cells and with what normalization?", "kind": "measurement", "id": "expression-and-localization-evidence-q01" }, { "text": "What localization and detection controls distinguish reduced MSH2 from technical non-detection?", "kind": "provenance", "id": "expression-and-localization-evidence-q02" } ] } ] } ] }, { "id": "msh2-variation-and-inference", "name": "MSH2 variation and inference", "description": "Relate molecular changes to measured consequences without exceeding the evidence.", "rationale": "MSH2 sequence changes, protein loss and repair defects are different observations that require explicit links.", "layers": [ { "id": "variant-to-function", "name": "Variant to function", "description": "Compare a specified altered MSH2 product with an appropriate reference.", "findings": [ { "id": "effect-specific-comparison", "name": "Effect-specific comparison", "description": "Record whether a change affects abundance, partner association, substrate recognition, nucleotide behaviour or integrated repair, including inconclusive results.", "questions": [ { "text": "Which reference-qualified MSH2 alteration was tested, and was it endogenous or engineered?", "kind": "provenance", "id": "effect-specific-comparison-q01" }, { "text": "Which functional measurements differ from the reference, with what controls and uncertainty?", "kind": "measurement", "id": "effect-specific-comparison-q02" } ] } ] }, { "id": "causal-attribution", "name": "Causal attribution", "description": "Assess whether an observed repair phenotype can be assigned to MSH2.", "findings": [ { "id": "msh2-specific-evidence", "name": "MSH2-specific evidence", "description": "Require evidence linking the phenotype to MSH2 rather than inferring causation from a general repair readout or a single expression result.", "questions": [ { "text": "What perturbation, restoration or orthogonal assay supports assigning the observed defect to MSH2?", "kind": "provenance", "id": "msh2-specific-evidence-q01" }, { "text": "Which additional observation would resolve competing explanations involving MSH2 abundance, its partners or downstream repair?", "kind": "action", "id": "msh2-specific-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": [ "The name has been interpreted as the human gene; the registry should confirm whether it instead denotes the protein or a homolog in another organism.", "The batch's device-oriented guidance does not fit this interpretation.", "This account is recalled knowledge; no sources were consulted." ], "questions": [ { "id": "evidence-confidence-notes-q01", "text": "Which of these check these first hold for the sense of MSH2 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": "HGNC approved gene symbol", "value_or_pattern": "MSH2", "note": "Human gene; the approved name is mutS homolog 2." }, { "scheme": "NCBI Gene", "value_or_pattern": "4436", "note": "Identifier for the human MSH2 gene." } ], "questions": [ { "id": "evidence-identifiers-q01", "text": "Which of these identifiers and schemes hold for the sense of MSH2 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": [ "Germline variant testing in assessment of hereditary cancer predisposition, particularly Lynch syndrome.", "Tumour immunohistochemistry for MSH2 protein as part of mismatch-repair deficiency assessment.", "Research into DNA repair, mutation accumulation and genome stability." ], "questions": [ { "id": "evidence-real-world-use-q01", "text": "Which of these real-world use hold for the sense of MSH2 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": [ "Loss of MSH2 function can impair mismatch repair and cause microsatellite instability.", "Heterozygous germline pathogenic variants can cause Lynch syndrome, with increased susceptibility to colorectal, endometrial and other cancers.", "Biallelic germline pathogenic variants can cause constitutional mismatch repair deficiency.", "Some deletions involving the neighbouring EPCAM gene can silence MSH2 without directly altering its coding sequence." ], "questions": [ { "id": "evidence-failure-modes-and-hazards-q01", "text": "Which of these failure modes and hazards hold for the sense of MSH2 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": "MSH2 protein", "difference": "The protein is the molecular product encoded by the MSH2 gene; gene variants and protein abundance describe different entities." }, { "name": "MSH6", "difference": "Encodes the partner that forms MutSĪ± with MSH2, principally recognizing base mismatches and small insertion-deletion loops." }, { "name": "MSH3", "difference": "Encodes the partner that forms MutSĪ² with MSH2, principally recognizing insertion-deletion loops." }, { "name": "MLH1", "difference": "Encodes a component of downstream mismatch-repair complexes rather than the MSH2-containing mismatch-recognition complexes." } ], "questions": [ { "id": "evidence-neighbours-q01", "text": "Which of these neighbouring kinds and how to tell them apart hold for the sense of MSH2 this model covers, and on what evidence?", "kind": "provenance" } ] } ] } ] } ] }, "openQuestions": [ "What original registry source establishes the species and gene-versus-protein meaning of MSH2?", "Does an existing Vercy model already own this molecular concept and require a registry link instead of a separate publication?", "Which reference transcripts and protein isoforms should anchor this entry, and which have direct functional evidence?", "Which assay conditions and controls support reproducible comparisons of MSH2 activity across studies?", "Which proposed MSH2 functions beyond mismatch repair have sufficient direct evidence to justify extending this draft?" ], "statistics": { "bundles": 5, "layers": 9, "findings": 13, "questions": 21 } }