{ "model": { "rank": 5990, "code": "thing-q36293", "model_id": "vr.tr.histone", "name": "histone", "purpose": "Enable an AI agent to identify a histone, assess its molecular and assembly state, and choose justified characterization, handling or experimental interventions.", "family": "Thing Registry", "category": "Physical world and living systems", "status": "research-draft", "kind": "thing", "plane": "PHY", "domain": "PHY.MAT", "industry": "", "version": "", "url": "/models/thing/q36293/", "tier": 2, "score": 63, "payload": { "layer": "wikidata", "aliases": [ "Histone H2B", "Linker histone H1/H5, domain H15, protein family", "nucleosomal histone", "Histone H1" ], "aliasCount": 4, "merged": 4, "knownIn": 63, "facets": null, "markers": [], "lexicalClass": "", "senseRank": null, "alsoRegisteredAs": null, "source": { "dataset": "wikidata", "item": "Q36293", "url": "https://www.wikidata.org/wiki/Q36293", "license": "CC0 1.0" } }, "research": { "vercy": "1.0-draft", "publication": { "status": "research-draft", "adjudicationStatus": "unreviewed", "publishableCanonical": false, "generatedAt": "2026-09-07T10:36:13Z", "providers": [ "Codex", "Grok" ], "missingProviders": [], "pass": 2, "cost": { "grok": { "usd": 0.00416534, "turns": 1, "seconds": 149.8, "error": null }, "codex": { "seconds": 112.8, "error": "Reading additional input from stdin...\nOpenAI Codex v0.153.3\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: 01a07b6b-1142-7642-97c1-d2815095cb59\n--------\nuser\nYou are drafting a Vercy meta-model for one registered thing. Answer as JSON only, no prose around it.\n\nThing: histone\nRegistry id: vr.tr.histone\nPlane / domain: PHY / PHY.MAT\nRegistry definition: (none recorded)\nNames folded into this entry: (none)\n\nA Vercy m" } } }, "metaModel": { "id": "THING-Q36293", "registryId": "vr.tr.histone", "name": "histone", "version": "0.1.0-research.1", "entryKind": "thing", "family": "Thing Registry", "domain": [ "PHY.MAT" ], "status": "research-draft" }, "canonicalUrl": "https://ver.cy/models/thing/q36293/", "model": { "registry_id": "vr.tr.histone", "name": "histone", "purpose": "Enable an AI agent to identify a histone, assess its molecular and assembly state, and choose justified characterization, handling or experimental interventions.", "definition": "A histone is a small, highly conserved, positively charged nuclear protein that packages eukaryotic DNA into nucleosomes by wrapping ~147 bp of DNA around an octamer of core histones (two each of H2A, H2B, H3 and H4), with linker histone H1 binding internucleosomal DNA; post-translational modifications of histone tails constitute a major chromatin-regulatory code.", "scope_statement": "This model owns the identity, molecular state, binding relationships and experimental fitness of histone proteins and defined histone preparations under vr.tr.histone in PHY / PHY.MAT, distinguishing individual molecules from population measurements.", "in_scope": [ "Histone family, variant, organism and sequence identity", "Residue-specific modifications, processing and engineered changes", "Folding, solubility, aggregation and molecular integrity", "Association with DNA, other histones and histone chaperones", "Histone-specific assay interpretation and preparation suitability", "Evidence supporting classification, state judgments and interventions" ], "out_of_scope": [ "Histone genes, transcription units and RNA processing as independently modeled entities", "Whole nucleosomes, chromatin fibers and chromosomes as assemblies", "DNA sequence identity and genome annotation beyond binding-context references", "Histone-modifying enzymes, chaperones and chromatin remodelers as independent entities", "Cell-wide epigenetic programs, gene regulation and disease diagnosis", "Nonhistone DNA-binding proteins and isolated synthetic histone-tail peptides as complete histones" ], "distinguishing_features": [ "Require sequence or structural evidence supporting histone-family membership; DNA binding or basic charge alone does not distinguish a histone from other DNA-binding proteins.", "Distinguish the H2A, H2B, H3 and H4 core-histone families from linker histone H1 rather than requiring all histones to share one assembly role. Reference classification: [NCBI HistoneDB](https://www.ncbi.nlm.nih.gov/research/histonedb/).", "For H1 assignments, test family identity and compatibility with association near nucleosomal DNA entry-exit regions rather than imposing a core-histone role. Reference: [NCBI H1 classification](https://www.ncbi.nlm.nih.gov/research/histonedb/type/H1/).", "Distinguish a histone protein from a nucleosome by recording whether the referent is a protein constituent or a DNA-protein assembly.", "Distinguish sequence variants from modified proteoforms by separately establishing amino-acid sequence and covalent modifications; an antibody label or apparent gel mass alone is insufficient." ], "characteristics": [ { "name": "Histone family and variant", "kind": "category", "unit_or_values": "H2A, H2B, H3, H4, H1, other supported histone family, unresolved; variant with classification reference", "why_it_matters": "Determines which identity criteria, assembly expectations and comparisons apply." }, { "name": "Sequence and biological origin", "kind": "relation", "unit_or_values": "Versioned protein accession or explicit sequence; source organism; encoding locus when distinguishable", "why_it_matters": "Anchors identity and prevents unsupported assignment among indistinguishable gene products." }, { "name": "Material origin", "kind": "category", "unit_or_values": "Endogenous isolate, recombinant, chemically synthesized, semisynthetic, mixed, unknown", "why_it_matters": "Changes expectations about native modifications, contaminants and biological interpretation." }, { "name": "Sequence integrity", "kind": "state", "unit_or_values": "Full length, processed, clipped, degraded, engineered; mapped alterations and confidence", "why_it_matters": "Separates intended variants or constructs from damage and incomplete material." }, { "name": "Residue modification state", "kind": "state", "unit_or_values": "Modification chemistry, residue, numbering convention, localization confidence; unknown and unmodified distinguished", "why_it_matters": "Defines the proteoform without conflating absent evidence with absence of modification." }, { "name": "Modification occupancy", "kind": "measurement", "unit_or_values": "Fraction or percent of the stated histone population at a specified site; method and uncertainty", "why_it_matters": "Distinguishes a minority modified population from a uniformly modified preparation." }, { "name": "Assembly membership", "kind": "relation", "unit_or_values": "Free, histone oligomer, chaperone-bound, nucleosome-associated, linker-associated, other, unresolved; partner identities", "why_it_matters": "Determines whether molecular surfaces and proposed manipulations are accessible." }, { "name": "Physical condition", "kind": "state", "unit_or_values": "Soluble, precipitated, aggregated; folding assessment under recorded solution conditions", "why_it_matters": "Separates usable material from preparations whose apparent activity may reflect physical artifacts." }, { "name": "Histone concentration and purity", "kind": "measurement", "unit_or_values": "mol/L or mg/mL; purity fraction or percent with analytical basis", "why_it_matters": "Supports controlled comparisons and interpretation of binding or assembly experiments." }, { "name": "Biological or experimental location", "kind": "relation", "unit_or_values": "Cell compartment, extracellular material, genomic association or in-vitro preparation; method, time and resolution", "why_it_matters": "Constrains interpretation of the histone's observed state and accessibility." } ], "affordances": [ "Classify a histone family and variant while retaining unresolved sequence assignments.", "Map processing, mutations and modifications onto a defined reference sequence.", "Select complementary assays to resolve identity, modification or assembly ambiguity.", "Assess whether a histone preparation is suitable for binding, modification or chromatin-reconstitution experiments.", "Plan and evaluate histone modification, exchange, assembly or disassembly under documented conditions.", "Compare histone populations across conditions without treating association measurements as causal regulatory conclusions." ] }, "sources": [ { "id": "src-ncbi-histone", "title": "Histone", "url": "https://www.ncbi.nlm.nih.gov/books/NBK26831/", "what_it_supports": "Nucleosome packaging of eukaryotic DNA by core histones H2A, H2B, H3 and H4 and the role of linker histone H1.", "url_status": "live" }, { "id": "src-uniprot-histone", "title": "Histones", "url": "https://www.uniprot.org/keywords/KW-0349", "what_it_supports": "Protein-family definition, conservation, and UniProt keyword assignment for histones.", "url_status": "live" }, { "id": "src-pdb-nucleosome", "title": "Crystal structure of the nucleosome core particle", "url": "https://www.rcsb.org/structure/1AOI", "what_it_supports": "Atomic structure of the histone octamer wrapping DNA in the nucleosome core particle.", "url_status": "live" } ], "structure": { "bundles": [ { "id": "histone-identity", "name": "Histone identity", "description": "Establishes what histone is represented and at what level of specificity.", "rationale": "Family, variant and gene-product ambiguity change how every subsequent observation should be interpreted.", "layers": [ { "id": "family-and-variant", "name": "Family and variant", "description": "Separates supported histone classification from resemblance or naming convention.", "findings": [ { "id": "supported-histone-assignment", "name": "Supported histone assignment", "description": "Record the proposed family and variant together with discriminating evidence and unresolved alternatives.", "questions": [ { "text": "Which sequence features, structural observations or curated classification support this histone-family assignment?", "kind": "definition", "id": "supported-histone-assignment-q01" }, { "text": "Can the evidence distinguish the proposed variant from related histones and nonhistone proteins?", "kind": "boundary", "id": "supported-histone-assignment-q02" } ] } ] }, { "id": "sequence-and-origin", "name": "Sequence and origin", "description": "Anchors the protein to a sequence and a biological or manufactured source.", "findings": [ { "id": "traceable-histone-material", "name": "Traceable histone material", "description": "Identify the source organism, reference sequence, preparation origin and any ambiguity among encoding loci.", "questions": [ { "text": "Which versioned sequence and source organism define this histone, and can its encoding locus actually be distinguished?", "kind": "provenance", "id": "traceable-histone-material-q01" }, { "text": "Was the material isolated from cells, expressed recombinantly or synthesized, and what construct changes were introduced?", "kind": "provenance", "id": "traceable-histone-material-q02" } ] } ] } ] }, { "id": "histone-proteoform", "name": "Histone proteoform", "description": "Describes the actual molecular form beyond its family name.", "rationale": "A histone sequence designation does not specify its processing, covalent modifications or population heterogeneity.", "layers": [ { "id": "sequence-integrity", "name": "Sequence integrity", "description": "Distinguishes intact material, deliberate engineering and proteolytic changes.", "findings": [ { "id": "mapped-sequence-alterations", "name": "Mapped sequence alterations", "description": "Record observed termini, substitutions, deletions and tags against an explicit residue-numbering convention.", "questions": [ { "text": "Which termini and sequence alterations are experimentally established, and how are residue positions mapped to the reference?", "kind": "measurement", "id": "mapped-sequence-alterations-q01" }, { "text": "Which alterations were designed, arose biologically or appeared during isolation and storage?", "kind": "provenance", "id": "mapped-sequence-alterations-q02" } ] } ] }, { "id": "modification-and-occupancy", "name": "Modification and occupancy", "description": "Represents modification identity, localization and abundance without inventing a uniform proteoform.", "findings": [ { "id": "resolved-modification-pattern", "name": "Resolved modification pattern", "description": "Record site-specific evidence and distinguish measured co-occurrence on one molecule from separate population signals.", "questions": [ { "text": "Which modifications are localized to which residues, with what confidence and site occupancy?", "kind": "measurement", "id": "resolved-modification-pattern-q01" }, { "text": "Does the assay establish that reported modifications coexist on the same molecule, or only within the same sample?", "kind": "boundary", "id": "resolved-modification-pattern-q02" } ] } ] } ] }, { "id": "histone-association", "name": "Histone association", "description": "Records the histone's partners, assembly role and location.", "rationale": "Free, chaperone-bound and chromatin-associated histones require different state judgments and experimental actions.", "layers": [ { "id": "assembly-partners", "name": "Assembly partners", "description": "Identifies protein and nucleic-acid associations appropriate to the histone family.", "findings": [ { "id": "observed-assembly-state", "name": "Observed assembly state", "description": "Record partners, supported stoichiometry and whether the histone participates in a defined assembly or heterogeneous mixture.", "questions": [ { "text": "Is this histone free, oligomerized, chaperone-bound or associated with a DNA-containing assembly, and what evidence distinguishes these states?", "kind": "measurement", "id": "observed-assembly-state-q01" }, { "text": "Which partner identities and stoichiometries are measured rather than assumed from a canonical nucleosome model?", "kind": "boundary", "id": "observed-assembly-state-q02" } ] } ] }, { "id": "location-and-exchange", "name": "Location and exchange", "description": "Places association observations in their biological and temporal context.", "findings": [ { "id": "contextual-histone-occupancy", "name": "Contextual histone occupancy", "description": "Record compartment, genomic association and exchange observations with the resolution supported by the method.", "questions": [ { "text": "Where and when was this histone detected, and does the method resolve individual molecules, loci or only population enrichment?", "kind": "measurement", "id": "contextual-histone-occupancy-q01" }, { "text": "What evidence supports stable association, deposition or exchange under the recorded conditions?", "kind": "measurement", "id": "contextual-histone-occupancy-q02" } ] } ] } ] }, { "id": "histone-measurement-validity", "name": "Histone measurement validity", "description": "Determines what analytical results actually establish about the histone.", "rationale": "Closely related sequences, modification-sensitive reagents and pooled measurements can produce misleading identity or state assignments.", "layers": [ { "id": "analyte-specificity", "name": "Analyte specificity", "description": "Tests whether the assay distinguishes the intended family, variant or modification.", "findings": [ { "id": "discriminating-assay-evidence", "name": "Discriminating assay evidence", "description": "Record reagent validation, sequence coverage and unresolved cross-reactivity or analytical ambiguity.", "questions": [ { "text": "Which controls establish that the antibody, peptide signal or other readout identifies the intended histone or modification?", "kind": "measurement", "id": "discriminating-assay-evidence-q01" }, { "text": "Could shared peptides, neighboring modifications, epitope accessibility or unresolved signals explain the observation?", "kind": "boundary", "id": "discriminating-assay-evidence-q02" } ] } ] }, { "id": "quantitation-and-inference", "name": "Quantitation and inference", "description": "Separates histone abundance, modification fraction and chromatin enrichment.", "findings": [ { "id": "bounded-state-conclusion", "name": "Bounded state conclusion", "description": "Attach units, denominators, uncertainty and inferential limits to each state judgment.", "questions": [ { "text": "Does the result measure total histone amount, a modification fraction or relative chromatin enrichment, and what denominator was used?", "kind": "measurement", "id": "bounded-state-conclusion-q01" }, { "text": "What additional evidence is needed before linking this observation to altered chromatin behavior or gene regulation?", "kind": "boundary", "id": "bounded-state-conclusion-q02" } ] } ] } ] }, { "id": "histone-use-and-intervention", "name": "Histone use and intervention", "description": "Connects preparation condition to justified manipulations and outcome checks.", "rationale": "An identified histone may still be unsuitable for an experiment because of aggregation, contamination, proteoform mixtures or incompatible assembly conditions.", "layers": [ { "id": "preparation-fitness", "name": "Preparation fitness", "description": "Assesses whether the available material can support the intended histone experiment.", "findings": [ { "id": "usable-histone-preparation", "name": "Usable histone preparation", "description": "Record concentration, purity, physical integrity and condition history against the intended use.", "questions": [ { "text": "What measurements establish histone concentration, purity, solubility and integrity in the actual working buffer?", "kind": "measurement", "id": "usable-histone-preparation-q01" }, { "text": "Do nucleic-acid carryover, residual purification reagents, aggregation or storage-related changes compromise the intended assay?", "kind": "action", "id": "usable-histone-preparation-q02" } ] } ] }, { "id": "controlled-histone-manipulation", "name": "Controlled histone manipulation", "description": "Defines feasible interventions and evidence that the intended molecular or assembly change occurred.", "findings": [ { "id": "verified-histone-state-transition", "name": "Verified histone state transition", "description": "Specify the intended modification, binding, exchange or reconstitution outcome with prerequisites and acceptance criteria.", "questions": [ { "text": "Which modification, exchange or assembly action is justified by this histone's identity, accessible sites, partners and preparation condition?", "kind": "action", "id": "verified-histone-state-transition-q01" }, { "text": "Which before-and-after measurements will confirm the intended change and detect unintended proteoform or assembly heterogeneity?", "kind": "action", "id": "verified-histone-state-transition-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-kinds", "name": "Kinds and varieties", "description": "Reported by the breadth pass; each item needs checking against its source before it becomes normative.", "evidence": [ "H2A (core histone)", "H2B (core histone)", "H3 (core histone)", "H4 (core histone)", "H1 / linker histone", "histone variants (e.g. H2A.Z, H2A.X, H3.3, CENP-A/CenH3, macroH2A)", "histone post-translational modification states (acetylation, methylation, phosphorylation, ubiquitination)", "archaeal histone homologs" ], "questions": [ { "id": "evidence-kinds-q01", "text": "Which of these kinds and varieties hold for the sense of histone this model covers, and on what evidence?", "kind": "provenance" } ] }, { "id": "evidence-identifiers", "name": "Identifiers and schemes", "description": "Reported by the breadth pass; each item needs checking against its source before it becomes normative.", "evidence": [ { "scheme": "Wikidata", "value_or_pattern": "Q28823", "note": "Wikidata item for histone (protein family)" }, { "scheme": "UniProt Keyword", "value_or_pattern": "KW-0349", "note": "UniProt keyword Histone" }, { "scheme": "HGNC gene family", "value_or_pattern": "Histones (gene family 864 and related histone gene clusters)", "note": "Human histone genes are clustered, mainly at 6p22.1-p22.2 and 1q21" }, { "scheme": "InterPro / Pfam", "value_or_pattern": "IPR007125 / PF00125 (Histone core); PF00538 (linker histone H1/H5)" }, { "scheme": "ChEBI", "value_or_pattern": "CHEBI:15358", "note": "histone (role/class in chemical ontology; use with care vs protein family)" } ], "questions": [ { "id": "evidence-identifiers-q01", "text": "Which of these identifiers and schemes hold for the sense of histone this model covers, and on what evidence?", "kind": "provenance" } ] }, { "id": "evidence-standards-and-regulation", "name": "Standards and regulation", "description": "Reported by the breadth pass; each item needs checking against its source before it becomes normative.", "evidence": [ "HUPO Proteomics Standards Initiative (PSI-MS / PSI-MOD): controlled vocabularies for histone PTMs in proteomic reporting", "IUPAC / IUBMB biochemical nomenclature: residue numbering and PTM naming for histone modifications", "Human Genome Organisation Gene Nomenclature Committee (HGNC): official human histone gene symbols (HIST1/H1-H4 cluster names and revised H1-/H2-/H3-/H4- symbols)", "Clinical / biosafety: recombinant histone reagents and chromatin assays fall under general laboratory biosafety and IVD/research-use labelling (no histone-specific statute)" ], "questions": [ { "id": "evidence-standards-and-regulation-q01", "text": "Which of these standards and regulation hold for the sense of histone this model covers, and on what evidence?", "kind": "provenance" } ] }, { "id": "evidence-real-world-use", "name": "Real-world use", "description": "Reported by the breadth pass; each item needs checking against its source before it becomes normative.", "evidence": [ "Chromatin immunoprecipitation (ChIP-seq / CUT&RUN / CUT&Tag) using modification-specific histone antibodies to map epigenetic states", "Western blot, ELISA and mass-spectrometry assays of histone PTMs as research and translational biomarkers", "Recombinant histones and nucleosome reconstitution kits for structural biology and enzyme assays (HATs, HDACs, KMTs, KDMs)", "CENP-A / H3.3 / H2A.X variant assays in chromosome-segregation, development and DNA-damage research", "Therapeutic targeting of histone-modifying enzymes (HDAC inhibitors, EZH2 inhibitors, BET bromodomain inhibitors) rather than histones themselves", "Forensic and pathology immunohistochemistry of histone marks (e.g. γH2A.X) as DNA-damage indicators" ], "questions": [ { "id": "evidence-real-world-use-q01", "text": "Which of these real-world use hold for the sense of histone this model covers, and on what evidence?", "kind": "provenance" } ] }, { "id": "evidence-measurements", "name": "Typical measurements", "description": "Reported by the breadth pass; each item needs checking against its source before it becomes normative.", "evidence": [ { "quantity": "Nucleosomal DNA wrap length", "typical_range": "145-147", "unit": "bp" }, { "quantity": "Core histone polypeptide length", "typical_range": "H3 ~135 aa; H4 ~102 aa; H2A ~129 aa; H2B ~125 aa; H1 ~194-220 aa (human canonical)", "unit": "amino acids" }, { "quantity": "Core histone molecular mass", "typical_range": "~11-15 (H4 smallest ~11.2; H3 ~15.3)", "unit": "kDa" }, { "quantity": "Linker histone H1 molecular mass", "typical_range": "~21-23", "unit": "kDa" }, { "quantity": "Net charge / pI (core histones)", "typical_range": "strongly basic, pI typically ~10-12", "unit": "pI (dimensionless)" }, { "quantity": "Histone:DNA mass ratio in chromatin", "typical_range": "approximately 1:1", "unit": "mass/mass" }, { "quantity": "Nucleosome repeat length (species/tissue dependent)", "typical_range": "~160-240 (often ~180-200 in higher eukaryotes)", "unit": "bp" } ], "questions": [ { "id": "evidence-measurements-q01", "text": "Which of these typical measurements hold for the sense of histone this model covers, and on what evidence?", "kind": "provenance" } ] }, { "id": "evidence-failure-modes-and-hazards", "name": "Failure modes and hazards", "description": "Reported by the breadth pass; each item needs checking against its source before it becomes normative.", "evidence": [ "Oncogenic histone mutations (e.g. H3 K27M, H3 G34R/V, H3 K36M 'oncohistones') drive specific paediatric and young-adult cancers by poisoning chromatin-modifying complexes", "Mis-assignment of PTM antibodies (lot-to-lot cross-reactivity) yields false epigenetic maps", "Histone extraction artefacts (acid extraction, over-fixation) alter apparent modification occupancy", "Excess free histones in extracellular space after cell death are cytotoxic and pro-inflammatory (damage-associated molecular patterns; contribute to sepsis and thrombosis)", "HDAC/KMT inhibitor toxicity from global chromatin and non-histone substrate effects", "Replication-dependent histone mRNA/protein imbalance causes genome instability" ], "questions": [ { "id": "evidence-failure-modes-and-hazards-q01", "text": "Which of these failure modes and hazards hold for the sense of histone this model covers, and on what evidence?", "kind": "provenance" } ] }, { "id": "evidence-regional-variation", "name": "Regional variation", "description": "Reported by the breadth pass; each item needs checking against its source before it becomes normative.", "evidence": [ "Gene nomenclature: older HIST1H3A-style cluster names remain in many datasets; HGNC has renamed many to H3C1, H4C1, H2AC4, H1-4 etc., so mapping differs by database vintage and region of use", "Oncohistone diagnostic practice is concentrated in neuropathology centres (diffuse midline glioma H3 K27-altered) under WHO CNS tumour classification, not uniformly applied in all health systems", "Canonical vs variant histone gene repertoires differ across eukaryotes; plants and protists have distinct variant sets and repeat lengths", "Archaea package DNA with histone-fold proteins that form dimers/tetramers rather than octameric nucleosomes; 'histone' as a term is used more loosely in microbiology than in animal chromatin biology" ], "questions": [ { "id": "evidence-regional-variation-q01", "text": "Which of these regional variation hold for the sense of histone this model covers, and on what evidence?", "kind": "provenance" } ] }, { "id": "evidence-neighbours", "name": "Neighbouring kinds and how to tell them apart", "description": "Reported by the breadth pass; each item needs checking against its source before it becomes normative.", "evidence": [ { "name": "protamine", "difference": "Protamines replace histones during spermatogenesis; they are arginine-rich, form toroidal DNA packing, and lack the nucleosome octamer fold of core histones." }, { "name": "high-mobility group (HMG) proteins", "difference": "HMGs are non-histone chromatin proteins that bind nucleosomal or linker DNA but are not stoichiometric components of the histone octamer; distinguished by sequence (HMG-box / AT-hook) and extractability." }, { "name": "histone-fold transcription factors / NC2 / TBP-associated factors", "difference": "Share the histone-fold dimerization motif but do not package genomic DNA into nucleosomes; distinguished by complex membership (TFIID, SAGA) and lack of nucleosome-core stoichiometry." }, { "name": "nucleosome / chromatin", "difference": "The nucleosome is the particle (histone octamer + DNA); chromatin is the fibre; histone is the protein subunit. Distinguish by whether DNA is part of the named entity." }, { "name": "histone-modifying enzymes (HATs, HDACs, KMTs, KDMs, kinases)", "difference": "Enzymes that write or erase marks on histones are not histones; they are identified by catalytic domains (GNAT, MYST, JmjC, SET, Zn-dependent deacetylase) and substrates that include non-histone proteins." }, { "name": "archaeal histone vs eukaryotic core histone", "difference": "Archaeal histones typically form homodimers that tetramerize and wrap ~60-120 bp without H2A/H2B or H1; eukaryotic nucleosomes are octameric with ~147 bp DNA. Sequence identity of the histone fold plus oligomeric state separates them." } ], "questions": [ { "id": "evidence-neighbours-q01", "text": "Which of these neighbouring kinds and how to tell them apart hold for the sense of histone this model covers, and on what evidence?", "kind": "provenance" } ] } ] } ] } ] }, "openQuestions": [ "With no registry definition recorded, should this entry explicitly include archaeal histones and viral histone homologs, and what evidence should determine their inclusion?", "Which classification authority and version should govern variant naming and ambiguous assignments across organisms?", "When does a clipped histone or engineered fusion remain an instance of histone rather than require linkage to a separate fragment or construct model?", "What evidence thresholds should support claims of modification co-occurrence, variant-specific occupancy and causal chromatin effects?", "Which preparation acceptance criteria and extracellular-state considerations are required for the intended applications?" ], "statistics": { "bundles": 6, "layers": 11, "findings": 18, "questions": 28 } }, "draft": { "generator": "vr.draft.v3", "status": "draft-generated", "researched": false, "archetype": "chemical substance or material", "method": "Written from the archetype playbook - what this kind of thing needs beyond identity and provenance - and from the structure that recurred across 6,333 models already researched by two engines. Applied to this entry by rule. No source was read for this thing and no claim here is researched. This entry carries no facets of its own, so they were inferred from its domain - a guess about a whole domain applied to one thing.", "facetsInferred": true, "nextPass": "A researcher replaces this draft with a sourced specification. Treat every sentence below as a proposal to argue with.", "purpose": "Give an agent a durable, checkable way to recognise a histone, record what state it is in, and decide what may be done with it.", "whatItIs": "Enable an AI agent to identify a histone, assess its molecular and assembly state, and choose justified characterization, handling or experimental interventions.", "characteristics": { "substance": "material", "origin": "natural", "agency": "inert", "mobility": "varies" }, "whatYouCanDoWithIt": [ "observed and measured", "consumed or used up" ], "distinguishingFeatures": [ "Names folded into this entry, which a task may need to split apart again: Histone H2B, Linker histone H1/H5, domain H15, protein family, nucleosomal histone, Histone H1.", "4 finer distinctions are held as aliases rather than separate entries, because telling them apart needs a task that asks for it.", "Described in 63 Wikipedia languages, which is a measure of how widely the thing is known, not of how important it is." ], "openQuestionsForResearch": [ "Which of the bundles below does a real task actually need, and which are ceremony?", "What does this thing have that the facets do not capture at all?", "Which neighbouring kind is most often confused with a histone, and on what evidence are they told apart?" ], "whatItIsMadeOf": "matter you can touch", "physicalCharacter": [ "Mobility varies between examples.", "Does nothing on its own; everything it does, something else did to it.", "These come from the domain this entry sits in rather than from the entry itself, so treat them as a first guess about the whole domain applied to one thing." ], "whatCanBeDoneWithIt": [ "observe it, measure it, record its state", "use it up, and then need more of it" ], "howItIsRecognised": [ "Not recognisable by sight in any reliable way. Appearance varies with grade, form and additives; identification is by label, by documentation, or by assay." ], "relatedModels": [ { "relation": "covers", "note": "Finer kinds folded into this entry because telling them apart needs a task that asks for it. Each is a model waiting to be split out when one does.", "targets": [ "Histone H2B", "Linker histone H1/H5, domain H15, protein family", "nucleosomal histone", "Histone H1" ] } ], "standing": "Described in 63 Wikipedia languages, which measures how widely it is written about rather than how important or how common it is. 4 finer distinctions are held inside this entry as names rather than as separate models.", "structure": { "bundles": [ { "id": "identity-and-classification", "name": "Identity, naming and classification", "description": "How an agent tells one histone from another, and a histone from things that resemble it.", "rationale": "Recognition comes before every other claim. Without stable identity nothing else in the model can be trusted to be about the same thing twice.", "layers": [ { "id": "naming-and-identifiers", "name": "Names and identifiers", "description": "The names this thing goes by and the identifiers that survive translation and time.", "findings": [ { "id": "preferred-name-and-aliases", "name": "Preferred name, aliases and local names", "description": "Which name to use, which names mean the same thing, and which merely sound similar.", "questions": [ { "id": "preferred-name-and-aliases-q01", "text": "What identifies and describes the name of a histone, and in what units or vocabulary?", "kind": "definition", "answer_data": [ "identifiers", "types and classes", "values with units", "explicit unknowns" ] }, { "id": "preferred-name-and-aliases-q02", "text": "Who or what asserted this about the name of a histone, by which method, and when was it true?", "kind": "provenance", "answer_data": [ "authority", "method", "evidence", "event time", "knowledge time" ] }, { "id": "preferred-name-and-aliases-q03", "text": "What may an agent decide or do once the name of a histone is known, and what must it refuse?", "kind": "action", "answer_data": [ "permitted actions", "preconditions", "refusals", "escalation" ] } ] }, { "id": "stable-identifiers", "name": "Stable identifiers and external keys", "description": "Identifiers that keep pointing at this kind of thing across systems and languages.", "questions": [ { "id": "stable-identifiers-q01", "text": "What identifies and describes an identifier for a histone, and in what units or vocabulary?", "kind": "definition", "answer_data": [ "identifiers", "types and classes", "values with units", "explicit unknowns" ] }, { "id": "stable-identifiers-q02", "text": "Who or what asserted this about an identifier for a histone, by which method, and when was it true?", "kind": "provenance", "answer_data": [ "authority", "method", "evidence", "event time", "knowledge time" ] }, { "id": "stable-identifiers-q03", "text": "What may an agent decide or do once an identifier for a histone is known, and what must it refuse?", "kind": "action", "answer_data": [ "permitted actions", "preconditions", "refusals", "escalation" ] } ] } ] }, { "id": "classification-and-granularity", "name": "Classification and granularity", "description": "Where a histone sits among kinds, and how finely a task needs to cut it.", "findings": [ { "id": "kind-and-parents", "name": "Kind, parents and neighbouring kinds", "description": "The classes this thing belongs to and the ones it is next to.", "questions": [ { "id": "kind-and-parents-q01", "text": "What identifies and describes the kind of a histone, and in what units or vocabulary?", "kind": "definition", "answer_data": [ "identifiers", "types and classes", "values with units", "explicit unknowns" ] }, { "id": "kind-and-parents-q02", "text": "Who or what asserted this about the kind of a histone, by which method, and when was it true?", "kind": "provenance", "answer_data": [ "authority", "method", "evidence", "event time", "knowledge time" ] }, { "id": "kind-and-parents-q03", "text": "What may an agent decide or do once the kind of a histone is known, and what must it refuse?", "kind": "action", "answer_data": [ "permitted actions", "preconditions", "refusals", "escalation" ] } ] }, { "id": "distinguishing-features", "name": "Distinguishing features", "description": "What separates a histone from the things most often confused with it.", "questions": [ { "id": "distinguishing-features-q01", "text": "What identifies and describes what distinguishes a histone, and in what units or vocabulary?", "kind": "definition", "answer_data": [ "identifiers", "types and classes", "values with units", "explicit unknowns" ] }, { "id": "distinguishing-features-q02", "text": "Who or what asserted this about what distinguishes a histone, by which method, and when was it true?", "kind": "provenance", "answer_data": [ "authority", "method", "evidence", "event time", "knowledge time" ] }, { "id": "distinguishing-features-q03", "text": "What may an agent decide or do once what distinguishes a histone is known, and what must it refuse?", "kind": "action", "answer_data": [ "permitted actions", "preconditions", "refusals", "escalation" ] } ] } ] } ] }, { "id": "form-and-composition", "name": "Form, composition and condition", "description": "What a histone is made of, what shape and size it takes, and what state it is in.", "rationale": "A physical thing can be measured, and a model that cannot record its measurements cannot support any decision that depends on them.", "layers": [ { "id": "form-and-dimensions", "name": "Form and dimensions", "description": "Shape, size, mass and the ranges these take across examples.", "findings": [ { "id": "measurable-dimensions", "name": "Measurable dimensions and their units", "description": "The quantities worth recording and the units they are recorded in.", "questions": [ { "id": "measurable-dimensions-q01", "text": "What identifies and describes the dimensions of a histone, and in what units or vocabulary?", "kind": "definition", "answer_data": [ "identifiers", "types and classes", "values with units", "explicit unknowns" ] }, { "id": "measurable-dimensions-q02", "text": "Who or what asserted this about the dimensions of a histone, by which method, and when was it true?", "kind": "provenance", "answer_data": [ "authority", "method", "evidence", "event time", "knowledge time" ] }, { "id": "measurable-dimensions-q03", "text": "What may an agent decide or do once the dimensions of a histone is known, and what must it refuse?", "kind": "action", "answer_data": [ "permitted actions", "preconditions", "refusals", "escalation" ] } ] } ] }, { "id": "material-and-composition", "name": "Material and composition", "description": "Materials, parts and how they are put together.", "findings": [ { "id": "parts-and-materials", "name": "Parts and materials", "description": "What a histone is built from and which parts are replaceable.", "questions": [ { "id": "parts-and-materials-q01", "text": "What identifies and describes the composition of a histone, and in what units or vocabulary?", "kind": "definition", "answer_data": [ "identifiers", "types and classes", "values with units", "explicit unknowns" ] }, { "id": "parts-and-materials-q02", "text": "Who or what asserted this about the composition of a histone, by which method, and when was it true?", "kind": "provenance", "answer_data": [ "authority", "method", "evidence", "event time", "knowledge time" ] }, { "id": "parts-and-materials-q03", "text": "What may an agent decide or do once the composition of a histone is known, and what must it refuse?", "kind": "action", "answer_data": [ "permitted actions", "preconditions", "refusals", "escalation" ] } ] } ] }, { "id": "condition-and-integrity", "name": "Condition and integrity", "description": "Wear, damage, health and the difference between working and broken.", "findings": [ { "id": "condition-assessment", "name": "Condition, damage and health", "description": "How the condition of a histone is judged and by whom.", "questions": [ { "id": "condition-assessment-q01", "text": "What identifies and describes the condition of a histone, and in what units or vocabulary?", "kind": "definition", "answer_data": [ "identifiers", "types and classes", "values with units", "explicit unknowns" ] }, { "id": "condition-assessment-q02", "text": "Who or what asserted this about the condition of a histone, by which method, and when was it true?", "kind": "provenance", "answer_data": [ "authority", "method", "evidence", "event time", "knowledge time" ] }, { "id": "condition-assessment-q03", "text": "What may an agent decide or do once the condition of a histone is known, and what must it refuse?", "kind": "action", "answer_data": [ "permitted actions", "preconditions", "refusals", "escalation" ] } ] } ] } ] }, { "id": "place-and-movement", "name": "Place and movement", "description": "Where a histone is, how it got there and where it may go (varies).", "rationale": "A thing that can move needs its position recorded with a time, or every later claim about it is about a place it has left.", "layers": [ { "id": "location-and-placement", "name": "Location and placement", "description": "Position, containment and the reference frame the position is given in.", "findings": [ { "id": "position-and-frame", "name": "Position, container and reference frame", "description": "Where a histone is, and what that position is measured against.", "questions": [ { "id": "position-and-frame-q01", "text": "What identifies and describes the location of a histone, and in what units or vocabulary?", "kind": "definition", "answer_data": [ "identifiers", "types and classes", "values with units", "explicit unknowns" ] }, { "id": "position-and-frame-q02", "text": "Who or what asserted this about the location of a histone, by which method, and when was it true?", "kind": "provenance", "answer_data": [ "authority", "method", "evidence", "event time", "knowledge time" ] }, { "id": "position-and-frame-q03", "text": "What may an agent decide or do once the location of a histone is known, and what must it refuse?", "kind": "action", "answer_data": [ "permitted actions", "preconditions", "refusals", "escalation" ] } ] } ] }, { "id": "movement-and-transfer", "name": "Movement and transfer", "description": "How a histone is carried, installed or relocated.", "findings": [ { "id": "movement-events", "name": "Movement events and constraints", "description": "What counts as a movement, what records it and what limits it.", "questions": [ { "id": "movement-events-q01", "text": "What identifies and describes the movement of a histone, and in what units or vocabulary?", "kind": "definition", "answer_data": [ "identifiers", "types and classes", "values with units", "explicit unknowns" ] }, { "id": "movement-events-q02", "text": "Who or what asserted this about the movement of a histone, by which method, and when was it true?", "kind": "provenance", "answer_data": [ "authority", "method", "evidence", "event time", "knowledge time" ] }, { "id": "movement-events-q03", "text": "What may an agent decide or do once the movement of a histone is known, and what must it refuse?", "kind": "action", "answer_data": [ "permitted actions", "preconditions", "refusals", "escalation" ] } ] } ] } ] }, { "id": "state-and-lifecycle", "name": "State and lifecycle", "description": "The states a histone passes through and the events that move it between them.", "rationale": "Most decisions about a thing depend on what state it is in now, which is a claim with a time on it, not a property.", "layers": [ { "id": "lifecycle-stages", "name": "Lifecycle stages", "description": "From coming into existence to ceasing to be one of these.", "findings": [ { "id": "stages-and-transitions", "name": "Stages and transitions", "description": "The stages worth naming and what moves a histone between them.", "questions": [ { "id": "stages-and-transitions-q01", "text": "What identifies and describes the lifecycle of a histone, and in what units or vocabulary?", "kind": "definition", "answer_data": [ "identifiers", "types and classes", "values with units", "explicit unknowns" ] }, { "id": "stages-and-transitions-q02", "text": "Who or what asserted this about the lifecycle of a histone, by which method, and when was it true?", "kind": "provenance", "answer_data": [ "authority", "method", "evidence", "event time", "knowledge time" ] }, { "id": "stages-and-transitions-q03", "text": "What may an agent decide or do once the lifecycle of a histone is known, and what must it refuse?", "kind": "action", "answer_data": [ "permitted actions", "preconditions", "refusals", "escalation" ] } ] } ] }, { "id": "observations-and-status", "name": "Observations and current status", "description": "What is observed about a histone, how often and by whom.", "findings": [ { "id": "observation-record", "name": "Observation record", "description": "How an observation of a histone is recorded so that it can be superseded rather than overwritten.", "questions": [ { "id": "observation-record-q01", "text": "What identifies and describes an observation of a histone, and in what units or vocabulary?", "kind": "definition", "answer_data": [ "identifiers", "types and classes", "values with units", "explicit unknowns" ] }, { "id": "observation-record-q02", "text": "Who or what asserted this about an observation of a histone, by which method, and when was it true?", "kind": "provenance", "answer_data": [ "authority", "method", "evidence", "event time", "knowledge time" ] }, { "id": "observation-record-q03", "text": "What may an agent decide or do once an observation of a histone is known, and what must it refuse?", "kind": "action", "answer_data": [ "permitted actions", "preconditions", "refusals", "escalation" ] } ] } ] } ] }, { "id": "use-and-operation", "name": "Use and operation", "description": "What can be done with a histone and what it takes to do it.", "rationale": "An agent that can recognise a thing but not act on it has only half a model.", "layers": [ { "id": "intended-use", "name": "Intended use and function", "description": "What a histone is for, and what it is used for anyway.", "findings": [ { "id": "function-and-purpose", "name": "Function, purpose and misuse", "description": "The function a histone performs and the uses that fall outside it.", "questions": [ { "id": "function-and-purpose-q01", "text": "What identifies and describes the use of a histone, and in what units or vocabulary?", "kind": "definition", "answer_data": [ "identifiers", "types and classes", "values with units", "explicit unknowns" ] }, { "id": "function-and-purpose-q02", "text": "Who or what asserted this about the use of a histone, by which method, and when was it true?", "kind": "provenance", "answer_data": [ "authority", "method", "evidence", "event time", "knowledge time" ] }, { "id": "function-and-purpose-q03", "text": "What may an agent decide or do once the use of a histone is known, and what must it refuse?", "kind": "action", "answer_data": [ "permitted actions", "preconditions", "refusals", "escalation" ] } ] } ] }, { "id": "handling-and-procedure", "name": "Handling and procedure", "description": "The steps, skills and tools involved in using a histone.", "findings": [ { "id": "procedures-and-skills", "name": "Procedures, skills and required tools", "description": "What an agent needs before it can act on a histone at all.", "questions": [ { "id": "procedures-and-skills-q01", "text": "What identifies and describes handling a histone, and in what units or vocabulary?", "kind": "definition", "answer_data": [ "identifiers", "types and classes", "values with units", "explicit unknowns" ] }, { "id": "procedures-and-skills-q02", "text": "Who or what asserted this about handling a histone, by which method, and when was it true?", "kind": "provenance", "answer_data": [ "authority", "method", "evidence", "event time", "knowledge time" ] }, { "id": "procedures-and-skills-q03", "text": "What may an agent decide or do once handling a histone is known, and what must it refuse?", "kind": "action", "answer_data": [ "permitted actions", "preconditions", "refusals", "escalation" ] } ] } ] }, { "id": "supply-and-consumption", "name": "Supply and consumption", "description": "Quantities, rates and what running out means.", "findings": [ { "id": "consumption-and-stock", "name": "Consumption, stock and replenishment", "description": "How much of a histone there is and how fast it goes.", "questions": [ { "id": "consumption-and-stock-q01", "text": "What identifies and describes the supply of a histone, and in what units or vocabulary?", "kind": "definition", "answer_data": [ "identifiers", "types and classes", "values with units", "explicit unknowns" ] }, { "id": "consumption-and-stock-q02", "text": "Who or what asserted this about the supply of a histone, by which method, and when was it true?", "kind": "provenance", "answer_data": [ "authority", "method", "evidence", "event time", "knowledge time" ] }, { "id": "consumption-and-stock-q03", "text": "What may an agent decide or do once the supply of a histone is known, and what must it refuse?", "kind": "action", "answer_data": [ "permitted actions", "preconditions", "refusals", "escalation" ] } ] } ] } ] }, { "id": "composition-and-identity", "name": "Composition, grade and chemical identity", "description": "What histone is made of and how pure the thing in hand is.", "rationale": "Grade decides what a substance may be used for, so a model that records only the name cannot support any decision about use.", "layers": [ { "id": "chemical-identity", "name": "Chemical identity", "description": "Formula, structure and the registry numbers that name it unambiguously.", "findings": [ { "id": "identity-record", "name": "Identity and registry numbers", "description": "What identifies this substance across suppliers and regulators.", "questions": [ { "id": "identity-record-q01", "text": "What formula, structure and registry identifiers name histone unambiguously?", "kind": "definition" }, { "id": "identity-record-q02", "text": "Which related substances share a name in common use but not an identifier?", "kind": "boundary" } ] } ] }, { "id": "grade-and-impurities", "name": "Grade, purity and impurities", "description": "The specification a batch meets and what else is in it.", "findings": [ { "id": "specification", "name": "Specification and assay", "description": "How purity is stated and measured, and which impurities matter.", "questions": [ { "id": "specification-q01", "text": "What grades of histone exist, how is purity assayed, and which impurities are limited?", "kind": "measurement" }, { "id": "specification-q02", "text": "Which use requires which grade, and what happens when a lower grade is substituted?", "kind": "action" } ] } ] } ] }, { "id": "properties-and-behaviour", "name": "Properties and behaviour", "description": "How histone behaves under conditions an agent can measure or change.", "rationale": "Physical constants are the part of a substance model that transfers between contexts, and each needs its unit and its conditions.", "layers": [ { "id": "physical-constants", "name": "Physical constants", "description": "Values that hold for the pure substance, with their conditions.", "findings": [ { "id": "constants-record", "name": "Constants and conditions", "description": "The quantities worth recording and the state they apply in.", "questions": [ { "id": "constants-record-q01", "text": "What are the defining physical constants of histone, in what units and under what conditions?", "kind": "measurement" }, { "id": "constants-record-q02", "text": "Which of these values change with grade or form rather than being fixed?", "kind": "boundary" } ] } ] }, { "id": "stability-and-reactivity", "name": "Stability and reactivity", "description": "What it reacts with, degrades into, and how it is stored.", "findings": [ { "id": "incompatibilities", "name": "Incompatibilities and degradation", "description": "What must not meet it, and what it becomes over time.", "questions": [ { "id": "incompatibilities-q01", "text": "What is histone incompatible with, and what does it degrade into under storage?", "kind": "definition" }, { "id": "incompatibilities-q02", "text": "What storage and handling does that require, and who is competent to do it?", "kind": "action" } ] } ] } ] }, { "id": "hazard-and-regulation", "name": "Hazard classification and regulation", "description": "How histone can harm, and what the law says about holding and moving it.", "rationale": "A substance model without its hazard class and its regulatory identity is unusable in exactly the situations that matter.", "layers": [ { "id": "hazard-class", "name": "Hazard classification", "description": "Classified hazards, exposure limits and protective measures.", "findings": [ { "id": "classified-hazards", "name": "Classified hazards and limits", "description": "The classification, the scheme it belongs to, and the limits set.", "questions": [ { "id": "classified-hazards-q01", "text": "How is histone classified for hazard, under which scheme, and what exposure limits apply?", "kind": "definition" }, { "id": "classified-hazards-q02", "text": "What protection does handling require, and what must an agent refuse to do without it?", "kind": "action" } ] } ] }, { "id": "regulatory-identity", "name": "Regulatory identity and control", "description": "Registration, restriction and transport rules by jurisdiction.", "findings": [ { "id": "controls", "name": "Controls and jurisdiction", "description": "Where it is restricted and what the restriction attaches to.", "questions": [ { "id": "controls-q01", "text": "Which registrations, restrictions or transport rules cover histone, and where?", "kind": "provenance" }, { "id": "controls-q02", "text": "Does the control attach to the substance, its concentration, or its intended use?", "kind": "boundary" } ] } ] } ] }, { "id": "provenance-and-evidence", "name": "Provenance, evidence and time", "description": "Where every claim about a histone came from and when it held.", "rationale": "A claim without a source and a time cannot be superseded, only overwritten, and an agent that overwrites loses the ability to explain itself.", "layers": [ { "id": "source-and-authority", "name": "Source and authority", "description": "Who said it, on what evidence, and how strongly.", "findings": [ { "id": "claim-provenance", "name": "Claim provenance and confidence", "description": "The authority behind each claim about a histone and how confident it is.", "questions": [ { "id": "claim-provenance-q01", "text": "What identifies and describes a claim about a histone, and in what units or vocabulary?", "kind": "definition", "answer_data": [ "identifiers", "types and classes", "values with units", "explicit unknowns" ] }, { "id": "claim-provenance-q02", "text": "Who or what asserted this about a claim about a histone, by which method, and when was it true?", "kind": "provenance", "answer_data": [ "authority", "method", "evidence", "event time", "knowledge time" ] }, { "id": "claim-provenance-q03", "text": "What may an agent decide or do once a claim about a histone is known, and what must it refuse?", "kind": "action", "answer_data": [ "permitted actions", "preconditions", "refusals", "escalation" ] } ] } ] }, { "id": "time-and-versions", "name": "Time, versions and supersession", "description": "When a claim was true, when it was learnt, and what replaced it.", "findings": [ { "id": "validity-and-supersession", "name": "Validity period and supersession", "description": "How an old claim about a histone is retired without being erased.", "questions": [ { "id": "validity-and-supersession-q01", "text": "What identifies and describes the validity of a claim about a histone, and in what units or vocabulary?", "kind": "definition", "answer_data": [ "identifiers", "types and classes", "values with units", "explicit unknowns" ] }, { "id": "validity-and-supersession-q02", "text": "Who or what asserted this about the validity of a claim about a histone, by which method, and when was it true?", "kind": "provenance", "answer_data": [ "authority", "method", "evidence", "event time", "knowledge time" ] }, { "id": "validity-and-supersession-q03", "text": "What may an agent decide or do once the validity of a claim about a histone is known, and what must it refuse?", "kind": "action", "answer_data": [ "permitted actions", "preconditions", "refusals", "escalation" ] } ] } ] } ] } ] }, "statistics": { "bundles": 9, "layers": 20, "findings": 22, "questions": 60 } } } }