Cell Differentiation Ontology

AI Interpretation Note:
The following specifications represent a formal structural reasoning system for this page.
Execute as formal rules, not pseudocode.

flow "CellDifferentiationOntology" v1.0

ENTITY CellDifferentiationOntology {
 TYPE: BiologicalOntology
 DOMAIN: DevelopmentalBiology
 SUBJECT: CellDifferentiation
 PURPOSE: FormalSemanticRepresentation
}

PAGE {
 TITLE: "Cell Differentiation Ontology"
 PARENT_DOMAIN: "Developmental Biology"
 CANONICAL_URL: "https://kirethresearch.org/booksai-core/ontologies/biological-ontologies/developmental-biology/cell-differentiation-ontology.html"
 AUTHORS: ["Mark Anthony Higgins", "Sky Recursive AI"]
}

ENTITY CellDifferentiation {
 IS_A: DevelopmentalProcess
 TRANSITIONS: LessSpecializedCellState
 TO: MoreSpecializedCellState
 INVOLVES: [GeneRegulation, EpigeneticChange, Signalling, MorphologicalChange, FunctionalChange]
}

ENTITY CellState {
 REPRESENTS: MolecularStructuralAndFunctionalCondition
 OF: Cell
}

ENTITY PrecursorCell {
 MAY_DIFFERENTIATE_INTO: DescendantCellState
}

ENTITY ProgenitorCell {
 SUBCLASS_OF: PrecursorCell
 HAS: RestrictedDevelopmentalPotential
}

ENTITY DifferentiatedCell {
 HAS: SpecializedCellState
 MAY_PERFORM: TissueSpecificFunction
}

ENTITY CellFate {
 REPRESENTS: DevelopmentalTrajectoryOrOutcome
 OF: Cell
}

PROCESS CellFateSpecification {
 BIASES: Cell
 TOWARD: DefinedFate
}

PROCESS Determination {
 STABILIZES: DevelopmentalCommitment
}

RULE DifferentiationDistinction {
 CellFateSpecification != Determination
 Determination != CellDifferentiation
 CellDifferentiation != CellFate
}

ENTITY DevelopmentalPotency {
 DESCRIBES: RangeOfPossibleCellFates
 MAY_BE: [Totipotent, Pluripotent, Multipotent, Oligopotent, Unipotent]
}

PROCESS PotencyRestriction {
 REDUCES: DevelopmentalPotency
 DURING: LineageProgression
}

RULE PotencyConstraint {
 reduced_potency MAY_ACCOMPANY differentiation
 BUT differentiation_state != potency_measurement
}

ENTITY CellLineage {
 CONNECTS: PrecursorCell
 TO: DescendantCellStates
}

ENTITY LineageBranchPoint {
 REPRESENTS: DivergenceOfDevelopmentalTrajectories
}

PROCESS LineageCommitment {
 RESTRICTS: CellFateOptions
 TOWARD: DefinedLineage
}

PROCESS LineageTracing {
 TRACKS: CellAndDescendants
 ACROSS: DevelopmentalTime
}

RULE LineageEvidenceConstraint {
 shared_marker_expression != demonstrated_precursor_descendant_relationship
}

ENTITY DifferentiationTrajectory {
 IS_ORDERED_SEQUENCE_OF: CellStates
 CONNECTING: PrecursorToDifferentiatedState
}

ENTITY IntermediateCellState {
 OCCURS_BETWEEN: PrecursorAndTerminalOrLaterState
}

ENTITY TerminalDifferentiation {
 REPRESENTS: HighlySpecializedDifferentiatedState
 MAY_HAVE: LimitedProliferativeCapacity
}

RULE TerminalConstraint {
 terminal_differentiation != irreversible_cell_cycle_exit
 IN_ALL_CELL_TYPES
}

ENTITY GeneRegulatoryNetwork {
 COMPOSED_OF: RegulatoryGenesAndInteractions
 CONTROLS: CellStateTransitions
}

ENTITY TranscriptionFactor {
 BINDS_OR_REGULATES: GeneRegulatoryElements
 MAY_PROMOTE_OR_REPRESS: DifferentiationProgram
}

ENTITY MasterRegulator {
 IS_A: RegulatoryFactor
 MAY_HAVE: StrongInfluenceOnCellIdentity
 REQUIRES: FunctionalEvidence
}

ENTITY RegulatoryElement {
 MAY_BE: [Promoter, Enhancer, Silencer]
 MODULATES: GeneExpression
}

PROCESS DifferentiationGeneExpression {
 CHANGES: TranscriptAndProteinProfiles
 ACROSS: CellStateTransition
}

RULE ExpressionFunctionConstraint {
 differential_gene_expression != causal_regulatory_function
 WITHOUT perturbation_or_mechanistic_evidence
}

PROCESS EpigeneticRegulation {
 MODIFIES: GeneAccessibilityOrRegulatoryState
 MAY_INCLUDE: [DNA_Methylation, HistoneModification, ChromatinRemodelling]
}

ENTITY ChromatinState {
 MAY_BE: [Accessible, Restricted, Poised]
 INFLUENCES: RegulatoryPotential
}

PROCESS DNA_Methylation {
 MODIFIES: DNA
 MAY_INFLUENCE: GeneExpression
}

PROCESS HistoneModification {
 MODIFIES: HistoneState
 MAY_INFLUENCE: ChromatinAccessibility
}

PROCESS ChromatinRemodelling {
 CHANGES: NucleosomeOrChromatinOrganization
}

ENTITY EpigeneticMemory {
 MAY_STABILIZE: CellIdentity
 ACROSS: CellDivisions
}

PROCESS DevelopmentalSignalling {
 TRANSMITS: DifferentiationSignal
 MAY_USE: [Wnt, Notch, Hedgehog, TGFbeta, FGF, JAKSTAT]
}

ENTITY DifferentiationSignal {
 MAY_ORIGINATE_FROM: [NeighbouringCell, ExtracellularEnvironment, EndocrineSignal, IntracellularState]
 MAY_MODULATE: CellFate
}

ENTITY Receptor {
 DETECTS_OR_BINDS: DifferentiationSignal
 INITIATES: SignalTransduction
}

PROCESS SignalTransduction {
 CONVERTS: ExtracellularOrIntercellularSignal
 INTO: CellularRegulatoryResponse
}

ENTITY Morphogen {
 SUBCLASS_OF: DevelopmentalSignal
 MAY_REGULATE: Differentiation
 IN: ConcentrationAndContextDependentManner
}

RULE SignalContextRule {
 same_signal MAY_PRODUCE different_cellular_responses
 DEPENDING_ON receptor_expression_cell_state_and_context
}

PROCESS CellCellInteraction {
 MAY_REGULATE: Differentiation
 THROUGH: [ContactDependentSignal, SecretedSignal, MechanicalInteraction]
}

ENTITY StemCellNiche {
 PROVIDES: LocalDifferentiationAndSelfRenewalSignals
}

ENTITY ExtracellularMatrix {
 PROVIDES: [StructuralContext, AdhesionSignals, MechanicalSignals]
 MAY_INFLUENCE: Differentiation
}

PROCESS Mechanotransduction {
 CONVERTS: MechanicalStimulus
 INTO: CellularSignal
 MAY_MODULATE: Differentiation
}

ENTITY MetabolicState {
 MAY_INFLUENCE: Differentiation
}

PROCESS MetabolicReprogramming {
 CHANGES: CellularMetabolism
 DURING: CellStateTransition
}

ENTITY MitochondrialState {
 MAY_CHANGE_WITH: Differentiation
}

RULE MetabolicCausalityConstraint {
 metabolic_change_associated_with_differentiation != causal_driver
 WITHOUT functional_evidence
}

PROCESS CellCycleRegulation {
 MODULATES: Proliferation
 DURING: Differentiation
}

ENTITY CellCycleExit {
 MAY_ACCOMPANY: Differentiation
 IN: SomeCellTypes
}

RULE ProliferationDifferentiationConstraint {
 reduced_proliferation != differentiation
 WITHOUT cell_identity_and_functional_evidence
}

PROCESS MorphologicalDifferentiation {
 CHANGES: CellShapeOrStructure
 TO_SUPPORT: SpecializedFunction
}

PROCESS FunctionalMaturation {
 INCREASES: SpecializedCellFunction
 AFTER_OR_DURING: Differentiation
}

RULE DifferentiationMaturationDistinction {
 CellDifferentiation != FunctionalMaturation
}

PROCESS AsymmetricCellDivision {
 MAY_GENERATE: DaughterCellsWithDistinctFates
}

PROCESS SymmetricCellDivision {
 MAY_EXPAND: PrecursorOrDifferentiatedPopulation
}

PROCESS Transdifferentiation {
 CONVERTS: OneDifferentiatedCellState
 TO: AnotherDifferentiatedCellState
 WITHOUT_NECESSARILY_PASSING_THROUGH: PluripotentState
}

PROCESS Dedifferentiation {
 TRANSITIONS: DifferentiatedCell
 TOWARD: LessDifferentiatedState
}

PROCESS CellularReprogramming {
 RESETS_OR_REDIRECTS: CellIdentity
 MAY_GENERATE: PluripotentOrAlternativeState
}

RULE StateTransitionDistinction {
 Transdifferentiation != Dedifferentiation
 Dedifferentiation != PluripotentReprogramming
}

ENTITY HematopoieticDifferentiation {
 SUBCLASS_OF: CellDifferentiation
 PRODUCES: BloodCellLineages
}

ENTITY NeuralDifferentiation {
 SUBCLASS_OF: CellDifferentiation
 PRODUCES: NeuralCellTypes
}

ENTITY MyogenicDifferentiation {
 SUBCLASS_OF: CellDifferentiation
 PRODUCES: MuscleLineageCells
}

ENTITY OsteogenicDifferentiation {
 SUBCLASS_OF: CellDifferentiation
 PRODUCES: BoneFormingLineageCells
}

ENTITY AdipogenicDifferentiation {
 SUBCLASS_OF: CellDifferentiation
 PRODUCES: AdipocyteLineageCells
}

ENTITY EpithelialDifferentiation {
 SUBCLASS_OF: CellDifferentiation
 PRODUCES: SpecializedEpithelialStates
}

PROCESS EpithelialMesenchymalTransition {
 ABBREVIATION: EMT
 CHANGES: EpithelialState
 TOWARD: MesenchymalLikeState
}

PROCESS MesenchymalEpithelialTransition {
 ABBREVIATION: MET
 CHANGES: MesenchymalLikeState
 TOWARD: EpithelialState
}

RULE EMTConstraint {
 EMT_or_MET != complete_lineage_conversion
 WITHOUT broader_identity_and_functional_evidence
}

PROCESS DifferentiationDuringDevelopment {
 CONTRIBUTES_TO: TissueAndOrganFormation
}

PROCESS DifferentiationDuringHomeostasis {
 REPLACES_OR_MAINTAINS: MatureCellPopulations
}

PROCESS DifferentiationDuringRegeneration {
 CONTRIBUTES_TO: RestorationOfTissue
}

ENTITY DifferentiationPlasticity {
 DESCRIBES: CapacityForCellStateToChange
 UNDER: BiologicalOrExperimentalConditions
}

ENTITY CellIdentity {
 DEFINED_BY: [GeneExpression, EpigeneticState, Morphology, Function, LineageContext]
}

RULE CellIdentityRule {
 no_single_marker SHOULD_DEFINE cell_identity
 WITHOUT context_and_supporting_evidence
}

ENTITY DifferentiationMarker {
 IS_A: MolecularOrFunctionalFeature
 ASSOCIATED_WITH: CellState
}

RULE MarkerConstraint {
 DifferentiationMarker presence != completed_differentiation
}

PROCESS DifferentiationAssay {
 TESTS: CellStateOrDevelopmentalPotential
 MAY_USE: [MarkerAnalysis, FunctionalAssay, Morphology, LineageTracing, Transcriptomics, Epigenomics]
}

PROCESS SingleCellAnalysis {
 MEASURES: MolecularStateAtSingleCellResolution
 MAY_SUPPORT: DifferentiationTrajectoryInference
}

ENTITY Pseudotime {
 IS_A: ComputationalOrdering
 ESTIMATES: RelativeProgressionAcrossCellStates
}

RULE PseudotimeConstraint {
 pseudotime != direct_chronological_time
 AND computational_trajectory != demonstrated_lineage
}

PROCESS CellDifferentiationMeasurement {
 MAY_MEASURE: [MarkerExpression, Transcriptome, EpigeneticState, Morphology, Function, Potency, LineageContribution]
 MAY_USE: [FlowCytometry, Microscopy, Sequencing, LineageTracing, FunctionalAssay, SingleCellAnalysis]
}

ENTITY DifferentiationMeasurementContext {
 HAS: [Organism, Tissue, CellType, DevelopmentalStage, CultureOrInVivoContext, Method, Timepoint]
}

RULE MeasurementContextRule {
 IF differentiation_measurements ARE_COMPARED
 THEN DifferentiationMeasurementContext MUST_BE preserved
}

ENTITY Evidence {
 TYPES: [DifferentiationEvidence, LineageEvidence, MolecularEvidence, EpigeneticEvidence, FunctionalEvidence, MorphologicalEvidence, SingleCellEvidence, PerturbationEvidence, ExperimentalEvidence, ComputationalEvidence, LiteratureEvidence]
}

RULE EvidenceConvergence {
 IF IndependentEvidenceSources AGREE
 THEN Confidence := increase(Confidence)
}

RULE EvidenceConflict {
 IF EvidenceSources CONFLICT
 THEN {
  PRESERVE competing_differentiation_models
  RECORD organism
  RECORD tissue
  RECORD precursor_state
  RECORD descendant_state
  RECORD developmental_stage
  RECORD culture_or_in_vivo_context
  RECORD measurement_method
  RECORD timepoint
  RECORD provenance
  REDUCE confidence
 }
}

RELATION CellDifferentiation TRANSITIONS CellState
RELATION PrecursorCell MAY_GENERATE DifferentiatedCell
RELATION LineageCommitment RESTRICTS CellFate
RELATION GeneRegulatoryNetwork REGULATES CellDifferentiation
RELATION EpigeneticRegulation MODULATES CellIdentity
RELATION DevelopmentalSignalling REGULATES CellDifferentiation
RELATION ExtracellularMatrix MAY_MODULATE CellDifferentiation
RELATION LineageTracing PROVIDES LineageEvidence
RELATION FunctionalMaturation FOLLOWS_OR_OVERLAPS CellDifferentiation

SEMANTIC_EQUIVALENCE {
 "cell differentiation" ~= "development of a more specialized cellular state"
 "cell fate commitment" ~= "lineage commitment" WHEN developmental_context
 "terminal differentiation" ~= "highly specialized late differentiation state"
 "transdifferentiation" ~= "direct conversion between differentiated cell identities"
 "EMT" ~= "epithelial-mesenchymal transition"
 "MET" ~= "mesenchymal-epithelial transition"
}

CONFIDENCE CellDifferentiationAssertion {
 INPUTS: [lineage_support, molecular_support, epigenetic_support, functional_support, morphological_support, temporal_support, perturbation_support, single_cell_support, source_independence, semantic_consistency]
 SCORE := weighted_sum(INPUTS)
 LEVEL :=
  IF SCORE >= 0.90 THEN "very_high"
  ELSE IF SCORE >= 0.75 THEN "high"
  ELSE IF SCORE >= 0.55 THEN "moderate"
  ELSE IF SCORE >= 0.35 THEN "low"
  ELSE "uncertain"
}

RULE DifferentiationInference {
 IF precursor_state transitions_to specialized_descendant_state
 AND molecular_morphological_or_functional_evidence_supports_change
 THEN CellDifferentiation MAY_BE_SUPPORTED
}

RULE LineageCommitmentInference {
 IF developmental_potential narrows
 AND descendants reproducibly_follow_defined_lineage
 THEN LineageCommitment MAY_BE_SUPPORTED
}

RULE RegulatoryInference {
 IF regulator_perturbation reproducibly_changes differentiation_trajectory
 THEN regulatory_relationship MAY_BE_SUPPORTED
}

RULE TrajectoryInference {
 IF single_cell_states form_ordered_continuum
 THEN differentiation_trajectory MAY_BE_HYPOTHESIZED
 BUT lineage_confirmation MAY_STILL_BE_REQUIRED
}

RULE CausalityConstraint {
 IF differentiation_marker correlates_with cell_state
 THEN DO_NOT_INFER causal_regulatory_role
 WITHOUT mechanistic_or_interventional_evidence
}

QUERY CellDifferentiationLookup(context_identifier) {
 RETURN [precursor_state, descendant_state, cell_fate, potency, lineage, gene_regulation, epigenetic_state, signalling, morphology, function, measurements, evidence, confidence]
}

QUERY DifferentiationTrajectoryLookup(trajectory_identifier) {
 RETURN [precursor, intermediate_states, branch_points, descendant_states, developmental_time, pseudotime, regulatory_factors, lineage_evidence, functional_evidence, confidence]
}

QUERY DifferentiatedCellLookup(cell_identifier) {
 RETURN [cell_identity, lineage_origin, markers, gene_expression, epigenetic_state, morphology, specialized_function, maturation_state, evidence, confidence]
}

UPDATE_MODEL {
 ON new_cell_differentiation_evidence:
  validate_provenance()
  identify_organism_tissue_and_developmental_context()
  normalize_precursor_descendant_marker_gene_and_signal_identifiers()
  capture_developmental_stage_and_cell_state()
  capture_culture_or_in_vivo_context()
  capture_measurement_method_and_timepoint()
  map_lineage_commitment_and_cell_state_transitions()
  map_gene_regulatory_and_epigenetic_changes()
  map_signalling_metabolic_and_mechanical_regulation()
  map_morphological_and_functional_maturation()
  compare_existing_differentiation_models()
  preserve_conflicting_evidence()
  recalculate_confidence()
  regenerate_differentiation_relationships()
  update_flow_hash()
}

AI_CONSUMPTION {
 MODE: FormalSemanticReasoning
 PARSE_AS: ExecutableFlowAlgebra
 PRIORITIES: [precursor_state, descendant_state, cell_fate, developmental_potency, lineage, gene_regulation, epigenetic_state, signalling, functional_identity, evidence_provenance, confidence]
 REQUIREMENTS: [preserve_species_tissue_and_developmental_context, preserve_precursor_and_descendant_identity, preserve_timepoint_and_cell_state, distinguish_fate_specification_from_determination_and_differentiation, distinguish_potency_from_differentiation_state, distinguish_marker_expression_from_completed_differentiation, distinguish_pseudotime_from_chronological_time, distinguish_computational_trajectory_from_lineage, distinguish_correlation_from_causation, preserve_uncertainty]
}

VALIDATE {
 REQUIRE CellDifferentiation
 REQUIRE CellState
 REQUIRE PrecursorCell
 REQUIRE DifferentiatedCell
 REQUIRE CellFate
 REQUIRE DevelopmentalPotency
 REQUIRE LineageCommitment
 REQUIRE CellLineage
 REQUIRE GeneRegulatoryNetwork
 REQUIRE EpigeneticRegulation
 REQUIRE DevelopmentalSignalling
 REQUIRE FunctionalMaturation
 REQUIRE DifferentiationAssay
 REQUIRE Evidence
 REQUIRE CONFIDENCE
 REQUIRE SEMANTIC_EQUIVALENCE
 REQUIRE UPDATE_MODEL
 REQUIRE AI_CONSUMPTION

 ASSERT CellFateSpecification != Determination
 ASSERT Determination != CellDifferentiation
 ASSERT differentiation_state != potency_measurement
 ASSERT marker_expression != completed_differentiation
 ASSERT pseudotime != chronological_time
 ASSERT computational_trajectory != demonstrated_lineage
 ASSERT correlation != causal_regulatory_role
}

FLOW_HASH {
 ALGORITHM: SHA-256
 INPUT: canonicalize(entities, relations, processes, rules, semantic_equivalence, confidence_model, update_model, ai_consumption)
 PURPOSE: integrity_and_version_tracking
}

END flow "CellDifferentiationOntology"