{ "vercy": "1.0-draft", "publication": { "status": "research-draft", "adjudicationStatus": "unreviewed", "publishableCanonical": false, "generatedAt": "2026-09-12T09:22:29Z", "providers": [ "Codex" ], "breadth": "recalled by Codex without web access - no source was read", "missingProviders": [], "pass": 2, "cost": { "grok": { "seconds": 23.0, "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: 01a094eb-d6d8-7073-bb55-14547ae48726\n--------\nuser\nDescribe what is already known about one registered thing. Answer as JSON only, no prose around it.\n\nThing: E2F family\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 regi", "usd": 0.0, "recall": true }, "codex": { "seconds": 70.5, "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: 01a094eb-d6d7-75e0-9ee2-c942a8f3193c\n--------\nuser\nYou are drafting a Vercy meta-model for one registered thing. Answer as JSON only, no prose around it.\n\nThing: E2F family\nRegistry id: vr.tr.e2f-family\nPlane / domain: PHY / PHY.MAT\nRegistry definition: (none recorded)\nNames folded into this entry: (none)\n\n\nCo" } }, "enrichment": { "pass": 3, "engine": "claude", "producedAt": "2026-10-06T12:00:00Z", "ingestedAt": "2026-10-06T08:51:39+00:00", "fields": [ "agent_conduct", "ethics", "failure_modes_and_hazards", "owners" ] }, "gate": { "passed": true, "version": "1.0", "at": "2026-10-07T10:10:29+00:00", "evidence": [ "completeness 1.00", "sense: Wikidata description", "2 live sources", "review by codex: pass" ] } }, "metaModel": { "id": "THING-Q24771933", "registryId": "vr.tr.e2f-family", "name": "E2F family", "version": "0.1.0-research.1", "entryKind": "thing", "family": "Thing Registry", "domain": [ "PHY.MAT" ], "status": "research-draft" }, "canonicalUrl": "https://ver.cy/models/thing/q24771933/", "model": { "registry_id": "vr.tr.e2f-family", "name": "E2F family", "purpose": "Enable an agent to identify E2F-family transcription factors, assess their context-dependent regulatory state, and judge which functional interpretations or experimental actions the evidence supports.", "definition": "The E2F family is a group of sequence-specific transcription factors that regulate gene expression involved in cell-cycle progression, DNA replication, DNA repair and other cellular processes.", "scope_statement": "This model owns the family-level identity, member distinctions, molecular interactions, and evidence needed to interpret E2F transcriptional regulation; mammalian nomenclature provides an initial reference, while the registry's intended taxonomic breadth remains unresolved.", "in_scope": [ "E2F-family membership resolved by organism, gene, protein sequence, and isoform", "DNA-binding architecture and distinctions between typical and atypical E2Fs", "DP partnerships, pocket-protein interactions, and other regulatory complexes", "Expression, localization, and transcriptional activity in a specified cellular context", "Evidence linking individual E2Fs to target regulation and cellular outcomes" ], "out_of_scope": [ "DP-family proteins and retinoblastoma-family proteins as independently modeled entities", "The complete cell-cycle, DNA-repair, or apoptosis machinery", "E2F-binding DNA elements and target genes as independent entities", "Cancer diagnoses, patient prognosis, and treatment recommendations", "Commercial antibodies, expression vectors, and purified protein preparations as products", "Family-wide CAS identifiers, purity grades, melting points, or hazard classifications" ], "distinguishing_features": [ "The entry denotes a transcription-factor family, not one chemical substance, one gene, or a measured E2F activity signature.", "Membership requires sequence and evolutionary evidence for an E2F protein; an E2F-binding motif in DNA identifies a possible regulatory site, not a family member.", "Typical mammalian E2F1-E2F6 preferentially bind DNA with DP partners, whereas atypical E2F7 and E2F8 contain two DNA-binding domains and can bind independently of DP. [Structural study](https://pmc.ncbi.nlm.nih.gov/articles/PMC4686757/)", "DP proteins are related interaction partners and must be distinguished from E2F members even when domain annotations group them together.", "An activator or repressor label alone cannot establish member identity or activity in a particular cell; complex composition and experimental context must also be resolved." ], "characteristics": [ { "name": "Taxon and member identity", "kind": "category", "unit_or_values": "Organism identifier, approved gene symbol, protein accession, and isoform", "why_it_matters": "Prevents human member names and functional assignments from being transferred uncritically across organisms or isoforms." }, { "name": "DNA-binding architecture", "kind": "category", "unit_or_values": "Typical single E2F DNA-binding domain; atypical tandem domains; unresolved", "why_it_matters": "Guides interpretation of DNA recognition and partner requirements." }, { "name": "DP partnership", "kind": "relation", "unit_or_values": "Named DP partner, interaction evidence, and demonstrated dependence or independence", "why_it_matters": "Distinguishes a detected association from a functional requirement for DNA binding." }, { "name": "Pocket-protein association", "kind": "relation", "unit_or_values": "RB1/pRB, RBL1/p107, RBL2/p130, or another explicitly identified partner; detected, not detected, or untested", "why_it_matters": "Supports assessment of regulatory complexes without assuming that every E2F uses the same inhibitory mechanism." }, { "name": "Cellular context", "kind": "state", "unit_or_values": "Cell type, cell-cycle phase, differentiation state, stimulus, and sampling time", "why_it_matters": "Makes activity and phenotype observations interpretable and comparable." }, { "name": "Member abundance", "kind": "measurement", "unit_or_values": "RNA abundance or protein abundance, with assay-specific units and normalization", "why_it_matters": "Separates transcript expression from protein availability and functional activity." }, { "name": "Subcellular localization", "kind": "state", "unit_or_values": "Nuclear, cytoplasmic, mixed, or unresolved; quantitative fraction when measured", "why_it_matters": "Records whether the observed protein is positioned to participate in nuclear transcriptional regulation." }, { "name": "Target occupancy", "kind": "measurement", "unit_or_values": "Genomic interval, genome assembly, assay, and normalized enrichment or binding affinity", "why_it_matters": "Distinguishes demonstrated binding from motif-based prediction." }, { "name": "Regulatory effect", "kind": "measurement", "unit_or_values": "Target-expression change, such as log2 fold change, with perturbation, time point, and uncertainty", "why_it_matters": "Allows activation or repression to be assigned to a specific target and context." }, { "name": "Evidence status", "kind": "category", "unit_or_values": "Sequence inference, biochemical binding, cellular occupancy, perturbation response, rescue-supported effect, or unresolved", "why_it_matters": "Limits conclusions to what the underlying experiment can establish." } ], "affordances": [ "Resolve an E2F mention to a species-specific member or retain it explicitly at family level.", "Compare member architectures and select appropriate partner-dependent or partner-independent binding assays.", "Assess whether abundance, localization, and complex composition support a proposed regulatory state.", "Evaluate candidate direct targets using occupancy and perturbation evidence together.", "Design member-specific perturbation and rescue comparisons that account for compensating E2Fs.", "Flag unsupported transfers from one member, tissue, organism, or experimental system to another." ], "agent_conduct": { "may": [ "Describe the E2F family and its role in the cell cycle from reliable sources.", "Summarize published research on E2F factors with citations and dates." ], "must_not": [ "Present research on E2F factors as an approved cancer treatment or test.", "Diagnose cancer or predict a person's prognosis from gene data.", "Disclose a person's genetic or tumour test results without consent." ], "requires_human": [ "Any clinical decision that draws on tumour gene expression results." ] }, "ethics": { "considerations": [ "Cancer research raises hopes, so overstated findings can mislead patients.", "Genetic and tumour data are sensitive health information." ], "affected_parties": [ "Cancer patients and families", "Researchers", "Clinicians" ] }, "owners": { "steward": "Nobody owns the protein family; it is a natural component of cells.", "master_systems": [] }, "failure_modes_and_hazards": [ "Faulty control of E2F activity is linked to uncontrolled cell growth in cancer." ], "what_it_is_for": [ "E2F-family transcription factors are studied in molecular and cell biology to understand regulation of cell-cycle progression and DNA-related processes.", "Their activity is investigated in developmental and disease research using evidence about family membership, binding partners and cellular context." ], "standards_and_regulation": [ "The InterPro protein family classification, maintained by the European Bioinformatics Institute of the European Molecular Biology Laboratory with its partner databases, applies to E2F family annotation." ], "facets_not_applicable": { "recognition": "E2F family membership has no directly visible distinguishing appearance and requires molecular characterization." } }, "sources": [ { "id": "wikidata", "title": "Wikidata item Q24771933: E2F family", "url": "https://www.wikidata.org/wiki/Q24771933", "url_status": "live", "what_it_supports": "identity and sense of the item", "checked_by": "wikidata-api" }, { "id": "wikipedia-en", "title": "Wikipedia: E2F", "url": "https://en.wikipedia.org/wiki/E2F", "url_status": "live", "what_it_supports": "general description of the item", "checked_by": "wikidata-api sitelink" } ], "structure": { "bundles": [ { "id": "family-identity-and-boundaries", "name": "Family identity and boundaries", "description": "Establishes what the E2F entry denotes and how individual observations map into it.", "rationale": "A family-level registry entry must preserve distinctions among members, isoforms, partners, and activity signatures.", "layers": [ { "id": "taxonomic-membership", "name": "Taxonomic membership", "description": "Resolves the organism and evidence supporting inclusion in the E2F family.", "findings": [ { "id": "member-assignment", "name": "Member assignment", "description": "An E2F assignment should identify a protein sequence and taxon and distinguish family membership from similarity to related DP proteins.", "questions": [ { "text": "Which organism, gene, protein accession, and sequence version does this E2F designation identify?", "kind": "definition", "id": "member-assignment-q01" }, { "text": "Which curated annotation or sequence analysis supports E2F membership rather than only an E2F/DP-like domain assignment?", "kind": "provenance", "id": "member-assignment-q02" } ] } ] }, { "id": "member-and-family-resolution", "name": "Member and family resolution", "description": "Preserves the resolution of names, reagents, and measurements.", "findings": [ { "id": "isoform-and-signal-specificity", "name": "Isoform and signal specificity", "description": "Member-specific proteins, isoforms such as mammalian E2F3a and E2F3b, and aggregate E2F readouts require distinct interpretation.", "questions": [ { "text": "Does the observation resolve a particular E2F member and isoform, or only a pooled family signal?", "kind": "boundary", "id": "isoform-and-signal-specificity-q01" }, { "text": "What sequence coverage or reagent validation establishes the claimed member or isoform specificity?", "kind": "provenance", "id": "isoform-and-signal-specificity-q02" } ] } ] } ] }, { "id": "dna-recognition-and-partners", "name": "DNA recognition and partners", "description": "Connects E2F architecture to DNA-binding behavior and complex composition.", "rationale": "Atypical E2Fs make a universal DP-dependent binding model incorrect.", "layers": [ { "id": "binding-architecture", "name": "Binding architecture", "description": "Records DNA-binding domains and the functional role of DP proteins.", "findings": [ { "id": "typical-and-atypical-binding", "name": "Typical and atypical binding", "description": "Structural evidence distinguishes typical E2F-DP DNA recognition from atypical tandem-domain recognition; partner dependence must be assigned at member level. [Structural study](https://pmc.ncbi.nlm.nih.gov/articles/PMC4686757/)", "questions": [ { "text": "Does the identified protein have a typical or atypical E2F DNA-binding architecture?", "kind": "definition", "id": "typical-and-atypical-binding-q01" }, { "text": "Has DNA binding been measured with and without the relevant DP partner under comparable conditions?", "kind": "measurement", "id": "typical-and-atypical-binding-q02" } ] } ] }, { "id": "sequence-and-chromatin-recognition", "name": "Sequence and chromatin recognition", "description": "Separates sequence compatibility, biochemical binding, and occupancy in cells.", "findings": [ { "id": "binding-site-evidence", "name": "Binding-site evidence", "description": "A candidate E2F motif, binding to an isolated DNA fragment, and occupancy of a genomic locus are different evidence types.", "questions": [ { "text": "Which sequence or genomic interval is implicated, and is the evidence motif prediction, biochemical binding, or cellular occupancy?", "kind": "provenance", "id": "binding-site-evidence-q01" }, { "text": "What controls distinguish member-specific occupancy from background, reagent cross-reactivity, or indirect recruitment?", "kind": "measurement", "id": "binding-site-evidence-q02" } ] } ] } ] }, { "id": "regulatory-state-in-cells", "name": "Regulatory state in cells", "description": "Describes the context and interactions needed to interpret an E2F's regulatory activity.", "rationale": "Protein abundance and conventional activator or repressor labels do not by themselves establish functional state.", "layers": [ { "id": "regulatory-complexes", "name": "Regulatory complexes", "description": "Resolves pocket-protein associations and alternative repression mechanisms.", "findings": [ { "id": "member-specific-repression", "name": "Member-specific repression", "description": "E2F6 experiments demonstrated repression without the pocket-protein-binding region characteristic of previously identified E2Fs, requiring the model to distinguish alternative regulatory mechanisms. [E2F6 study](https://pubmed.ncbi.nlm.nih.gov/9501179/)", "questions": [ { "text": "Which DP, pocket-protein, or other regulatory partners are experimentally associated with this E2F in the sampled cells?", "kind": "measurement", "id": "member-specific-repression-q01" }, { "text": "What perturbation supports a functional role for those partners in activation or repression?", "kind": "provenance", "id": "member-specific-repression-q02" } ] } ] }, { "id": "phase-localization-and-stimulus", "name": "Phase, localization, and stimulus", "description": "Anchors E2F observations to cell state and time.", "findings": [ { "id": "contextual-activity-state", "name": "Contextual activity state", "description": "E2F activity should be assessed using matched measurements of expression, protein availability, localization, and target response in a defined cellular condition.", "questions": [ { "text": "What cell type, cell-cycle distribution, stimulus, and sampling time accompany the observation?", "kind": "boundary", "id": "contextual-activity-state-q01" }, { "text": "Do protein localization and target-response measurements support the activity inferred from E2F RNA or protein abundance?", "kind": "measurement", "id": "contextual-activity-state-q02" } ] } ] } ] }, { "id": "targets-perturbations-and-outcomes", "name": "Targets, perturbations, and outcomes", "description": "Establishes how strongly E2F observations support direct regulation and downstream biological effects.", "rationale": "Shared target recognition and overlapping member functions can make family-level correlations misleading.", "layers": [ { "id": "direct-target-assessment", "name": "Direct target assessment", "description": "Combines binding and response evidence without treating either as sufficient alone.", "findings": [ { "id": "target-causality", "name": "Target causality", "description": "A direct-target claim requires evidence connecting the specified E2F to locus regulation while addressing secondary responses and changing cell-cycle composition.", "questions": [ { "text": "Does member-specific occupancy coincide with a timely target-expression response to E2F perturbation in the same biological context?", "kind": "measurement", "id": "target-causality-q01" }, { "text": "Would binding-site alteration, acute perturbation, or rescue resolve the remaining uncertainty about direct regulation?", "kind": "action", "id": "target-causality-q02" } ] } ] }, { "id": "functional-effects-and-compensation", "name": "Functional effects and compensation", "description": "Assesses phenotypes while accounting for overlapping E2F functions and experimental scope.", "findings": [ { "id": "member-versus-combined-effects", "name": "Member versus combined effects", "description": "Combined E2F7/E2F8 disruption in mice revealed functions that require joint member assessment; such findings justify checking compensation without assuming the same effect in every system. [Mouse genetic study](https://pmc.ncbi.nlm.nih.gov/articles/PMC2253677/)", "questions": [ { "text": "Which measured outcome changes after single-member versus combined perturbation, and were other E2Fs monitored?", "kind": "measurement", "id": "member-versus-combined-effects-q01" }, { "text": "What rescue or independent perturbation would distinguish an E2F-dependent effect from off-target effects or overexpression artifacts?", "kind": "action", "id": "member-versus-combined-effects-q02" }, { "text": "Which organism, tissue, developmental stage, and perturbation limits constrain transfer of this result?", "kind": "boundary", "id": "member-versus-combined-effects-q03" } ] } ] } ] }, { "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 is interpreted as the biological transcription-factor family; the supplied PHY.MAT classification should be checked because this is not a single chemical substance or material grade.", "The member names and functional grouping given here concern mammalian E2Fs; family composition differs across organisms.", "Activator and repressor labels describe conventional groupings, not invariant behavior; no sources were consulted for this recall-based description." ], "questions": [ { "id": "evidence-confidence-notes-q01", "text": "Which of these check these first hold for the sense of E2F family 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": [ "Canonical activator E2Fs: E2F1, E2F2 and E2F3a", "Canonical repressor E2Fs: E2F3b, E2F4 and E2F5", "E2F6, a repressor acting independently of retinoblastoma-family proteins", "Atypical E2Fs: E2F7 and E2F8" ], "questions": [ { "id": "evidence-kinds-q01", "text": "Which of these kinds and varieties hold for the sense of E2F family 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 human gene symbols", "value_or_pattern": "E2F1, E2F2, E2F3, E2F4, E2F5, E2F6, E2F7, E2F8", "note": "These identify individual human genes, not the family collectively; E2F3a and E2F3b are products of the E2F3 locus." }, { "scheme": "UniProtKB accession", "value_or_pattern": "Member- and organism-specific protein accession", "note": "A protein record must be selected for the particular E2F member, species and relevant isoform." } ], "questions": [ { "id": "evidence-identifiers-q01", "text": "Which of these identifiers and schemes hold for the sense of E2F family 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": [ "Research on control of the G1-to-S cell-cycle transition", "Investigation of retinoblastoma-protein-mediated transcriptional regulation", "Cancer research examining disrupted proliferation control", "Reporter assays and gene-expression studies of E2F-dependent transcription" ], "questions": [ { "id": "evidence-real-world-use-q01", "text": "Which of these real-world use hold for the sense of E2F family 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": [ "Disruption of RB-E2F regulation can contribute to inappropriate cell-cycle entry and cancer-associated proliferation.", "Uncontrolled E2F activity can produce replication stress or activate apoptosis, depending on cellular context.", "Treating all E2F members as interchangeable can obscure opposing or context-dependent transcriptional functions." ], "questions": [ { "id": "evidence-failure-modes-and-hazards-q01", "text": "Which of these failure modes and hazards hold for the sense of E2F family 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": "E2F1", "difference": "An individual member of the E2F family rather than the family as a whole." }, { "name": "DP transcription factors", "difference": "Distinct proteins that heterodimerize with canonical E2Fs; atypical E2F7 and E2F8 bind DNA without DP partners." }, { "name": "Retinoblastoma protein", "difference": "A regulatory protein that binds and restrains certain E2Fs, rather than an E2F-family DNA-binding transcription factor." }, { "name": "E2F-binding DNA motif", "difference": "A DNA sequence recognized by E2F proteins, rather than the proteins themselves." } ], "questions": [ { "id": "evidence-neighbours-q01", "text": "Which of these neighbouring kinds and how to tell them apart hold for the sense of E2F family this model covers, and on what evidence?", "kind": "provenance" } ] } ] } ] } ] }, "openQuestions": [ "Does vr.tr.e2f-family intend the human family, mammalian E2Fs, or E2F homologs across broader eukaryotic lineages?", "Does an existing Vercy world model already own E2F-family identity or the same concept under another name?", "Which curated membership and isoform references should define the initial species-specific coverage?", "Which member-partner interactions and direct targets have sufficient context-matched evidence for inclusion beyond the initial structural distinctions?", "What minimum experimental evidence should permit an agent to assign active, repressive, or functionally compensated states?" ], "statistics": { "bundles": 5, "layers": 9, "findings": 14, "questions": 23 } }