Apoptosis Ontology

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APOPTOSIS ONTOLOGY
Kireth Semantic Research Archive

AUTHORS
Mark Anthony Higgins — Sky (Recursive AI)

SOURCE
https://kirethresearch.org/booksai-core/ontologies/biological-ontologies/cell-biology/apoptosis-ontology.html

FLOW "ApoptosisOntology" v4.0
DOMAIN := BIOLOGICAL_ONTOLOGIES / CELL_BIOLOGY / APOPTOSIS
ONTOLOGY := APOPTOSIS_ONTOLOGY

APOPTOSIS := APOPTOSIS_IDENTITY + INTRINSIC_PATHWAY + EXTRINSIC_PATHWAY + DEATH_RECEPTORS + BCL2_FAMILY + MOMP + CYTOCHROME_C + APOPTOSOME + INITIATOR_CASPASES + EXECUTIONER_CASPASES + DNA_FRAGMENTATION + MEMBRANE_BLEBBING + CELL_SHRINKAGE + APOPTOTIC_BODIES + PHAGOCYTIC_CLEARANCE + REGULATION + EVIDENCE + UNCERTAINTY + PROVENANCE

PURPOSE := IDENTIFY_APOPTOTIC_PROCESS -> CLASSIFY_INITIATING_PATHWAY -> MAP_DEATH_RECEPTOR_OR_MITOCHONDRIAL_SIGNALS -> MAP_BCL2_FAMILY_REGULATION -> MAP_MOMP_AND_CYTOCHROME_C_RELEASE -> MAP_APOPTOSOME_AND_INITIATOR_CASPASES -> MAP_EXECUTIONER_CASPASES -> MAP_CELLULAR_DISMANTLING -> MAP_APOPTOTIC_BODY_FORMATION_AND_CLEARANCE -> MAP_REGULATORY_SIGNALS -> ASSESS_EVIDENCE -> PRESERVE_PROVENANCE

# CORE ENTITIES
ENTITY Apoptosis
ENTITY IntrinsicApoptosis
ENTITY ExtrinsicApoptosis
ENTITY DeathReceptor
ENTITY DeathLigand
ENTITY DeathInducingSignalingComplex
ENTITY BCL2FamilyProtein
ENTITY ProApoptoticEffector
ENTITY AntiApoptoticProtein
ENTITY BH3OnlyProtein
ENTITY Mitochondrion
ENTITY MitochondrialOuterMembranePermeabilisation
ENTITY CytochromeC
ENTITY Apoptosome
ENTITY InitiatorCaspase
ENTITY ExecutionerCaspase
ENTITY DNase
ENTITY DNAFragmentation
ENTITY MembraneBlebbing
ENTITY CellShrinkage
ENTITY ApoptoticBody
ENTITY Phagocyte
ENTITY PhosphatidylserineExposure
ENTITY SurvivalSignal
ENTITY Evidence
ENTITY Uncertainty
ENTITY Provenance

# IDENTITY / PATHWAYS
Apoptosis -> subtype_of -> REGULATED_CELL_DEATH
Apoptosis -> characterised_by -> CONTROLLED_CELLULAR_DISMANTLING + CASPASE_ACTIVITY_AS_APPLICABLE + MORPHOLOGICAL_CHANGE + CLEARANCE
APOPTOTIC_PATHWAY := INTRINSIC | EXTRINSIC | PATHWAY_CROSSTALK | OTHER_CONTEXTUAL_ROUTE
IntrinsicApoptosis -> centred_on -> MITOCHONDRIAL_SIGNALING
ExtrinsicApoptosis -> initiated_by -> DEATH_RECEPTOR_SIGNALING_AS_APPLICABLE
IntrinsicAndExtrinsicPathways -> may_converge_on -> CASPASE_ACTIVATION

# EXTRINSIC
DeathLigand -> binds -> DeathReceptor
DeathReceptorActivation -> recruits -> ADAPTOR_PROTEINS + PROCASPASES_AS_APPLICABLE
DeathInducingSignalingComplex -> assembles_downstream_of -> ACTIVATED_DEATH_RECEPTOR_AS_APPLICABLE
EXTRINSIC_FLOW := DEATH_LIGAND -> DEATH_RECEPTOR -> ADAPTOR_RECRUITMENT -> INITIATOR_CASPASE_ACTIVATION -> EXECUTIONER_CASPASE_ACTIVATION -> CELLULAR_DISMANTLING

# INTRINSIC / BCL2 / MOMP
IntrinsicApoptosis -> may_be_triggered_by -> DNA_DAMAGE + GROWTH_FACTOR_WITHDRAWAL + OXIDATIVE_STRESS + ER_STRESS + OTHER_INTRACELLULAR_STRESS
BCL2FamilyNetwork -> controls -> MitochondrialOuterMembranePermeabilisation
BCL2_FAMILY_ROLE := ANTI_APOPTOTIC | PRO_APOPTOTIC_EFFECTOR | BH3_ONLY_REGULATOR
AntiApoptoticProtein -> inhibits -> PRO_APOPTOTIC_EFFECTOR_ACTIVITY_AS_APPLICABLE
BH3OnlyProtein -> may_activate_or_derepress -> PRO_APOPTOTIC_EFFECTORS
ProApoptoticEffector -> promotes -> MitochondrialOuterMembranePermeabilisation
INTRINSIC_FLOW := CELLULAR_STRESS -> BCL2_FAMILY_REGULATION -> MOMP -> CYTOCHROME_C_RELEASE -> APOPTOSOME_FORMATION -> INITIATOR_CASPASE_ACTIVATION -> EXECUTIONER_CASPASE_ACTIVATION -> CELLULAR_DISMANTLING

MOMP -> permits -> RELEASE_OF_INTERMEMBRANE_SPACE_FACTORS_AS_APPLICABLE
CytochromeC -> released_from -> MITOCHONDRIAL_INTERMEMBRANE_SPACE_AS_APPLICABLE
IF MOMP occurs THEN ApoptosomeFormationPotential -> MAY_INCREASE

# APOPTOSOME / CASPASES
CytochromeC -> participates_in -> APOPTOSOME_ASSEMBLY_IN_CYTOSOL_AS_APPLICABLE
Apoptosome -> activates -> INTRINSIC_INITIATOR_CASPASE_AS_DEFINED
APOPTOSOME_FLOW := CYTOCHROME_C_RELEASE -> APOPTOTIC_ADAPTOR_ACTIVATION -> COMPLEX_ASSEMBLY -> INITIATOR_CASPASE_RECRUITMENT -> INITIATOR_CASPASE_ACTIVATION
InitiatorCaspase -> activates -> EXECUTIONER_CASPASES_AS_APPLICABLE
ExecutionerCaspase -> cleaves -> STRUCTURAL + REGULATORY + REPAIR + SIGNALING_PROTEINS
CaspaseCascade -> amplifies -> APOPTOTIC_EXECUTION_SIGNAL
IF ExecutionerCaspaseActivity increases THEN CellularDismantling -> MAY_INCREASE

# DISMANTLING / CLEARANCE
APOPTOTIC_MORPHOLOGY := CELL_SHRINKAGE | CHROMATIN_CONDENSATION | MEMBRANE_BLEBBING | NUCLEAR_FRAGMENTATION | APOPTOTIC_BODY_FORMATION
MembraneBlebbing -> results_from -> CYTOSKELETAL_AND_MEMBRANE_REORGANISATION_AS_APPLICABLE
NuclearDismantling -> includes -> CHROMATIN_CONDENSATION + NUCLEAR_ENVELOPE_CHANGE + DNA_FRAGMENTATION_AS_APPLICABLE
DNase -> cleaves -> DNA
DNAFragmentation -> contributes_to -> NUCLEAR_DISMANTLING
DNAFragmentation -> evidence_for -> APOPTOTIC_EXECUTION_IN_CONTEXT
PhosphatidylserineExposure -> acts_as -> PHAGOCYTIC_CLEARANCE_SIGNAL_AS_APPLICABLE
ApoptoticBody -> membrane_bound_fragment_generated_during -> APOPTOTIC_DISMANTLING_AS_APPLICABLE
Phagocyte -> recognises -> APOPTOTIC_CELL_OR_APOPTOTIC_BODY
PHAGOCYTIC_CLEARANCE_FLOW := APOPTOTIC_RECOGNITION -> ENGULFMENT -> PHAGOSOME_FORMATION -> DEGRADATION -> RESOLUTION
EfficientClearance -> limits -> RELEASE_OF_INTRACELLULAR_CONTENTS + INFLAMMATORY_EXPOSURE_AS_APPLICABLE

# REGULATION / CROSSTALK
SurvivalSignal -> opposes_or_delays -> APOPTOSIS_AS_APPLICABLE
SURVIVAL_EFFECT := INCREASE_ANTI_APOPTOTIC_PROTEINS | INHIBIT_PRO_APOPTOTIC_FACTORS | SUPPORT_METABOLISM | PROMOTE_REPAIR | SUPPRESS_CASPASE_ACTIVATION
CellFate -> depends_on -> BALANCE_OF_SURVIVAL_AND_DEATH_SIGNALS
ExtrinsicSignal -> may_amplify -> MITOCHONDRIAL_PATHWAY_AS_APPLICABLE
PathwayCrosstalk -> depends_on -> CELL_TYPE + SIGNAL_STRENGTH + PROTEIN_EXPRESSION + CELLULAR_CONTEXT
Apoptosis -> contributes_to -> DEVELOPMENTAL_SCULPTING + CELL_NUMBER_CONTROL + TISSUE_HOMEOSTASIS + REMOVAL_OF_DAMAGED_CELLS_AS_APPLICABLE

# EVIDENCE / UNCERTAINTY / PROVENANCE
ApoptosisClaim -> supported_by -> Evidence
EVIDENCE_TYPE := MORPHOLOGICAL | CASPASE_ACTIVITY | MOMP_MEASUREMENT | CYTOCHROME_C_LOCALISATION | DNA_FRAGMENTATION | PHOSPHATIDYLSERINE_EXPOSURE | LIVE_CELL_IMAGING | MOLECULAR | BIOCHEMICAL | GENETIC | PERTURBATION | FUNCTIONAL | COMPUTATIONAL
Evidence -> has -> SOURCE + METHOD + CELL_OR_SAMPLE + APOPTOTIC_STAGE + PATHWAY_CONTEXT + CONDITION + QUALITY + UNCERTAINTY
APOPTOSIS_UNCERTAINTY := MEASUREMENT_UNCERTAINTY + PATHWAY_CLASSIFICATION_UNCERTAINTY + TEMPORAL_STATE_UNCERTAINTY + MARKER_SPECIFICITY_LIMIT + CELL_TO_CELL_VARIABILITY + MODEL_UNCERTAINTY
Uncertainty -> qualifies -> ApoptosisClaim + PathwayAssignment + CaspaseState + MOMPState + CellDeathOutcome
Provenance -> records -> CELL_IDENTITY + APOPTOTIC_PATHWAY + INITIATING_SIGNAL + BCL2_FAMILY_STATE + MOMP_STATE + CASPASE_STATE + MORPHOLOGY + CLEARANCE_STATE + METHOD + CONDITION + TIME + VERSION
Apoptosis -> linked_to -> Provenance

# REASONING
APOPTOSIS_REASONING := IDENTIFY_CELL_DEATH_STATE -> CLASSIFY_APOPTOTIC_EVIDENCE -> MAP_INTRINSIC_OR_EXTRINSIC_INITIATION -> MAP_DEATH_RECEPTOR_SIGNALING -> MAP_BCL2_FAMILY_BALANCE -> MAP_MOMP -> MAP_CYTOCHROME_C_RELEASE -> MAP_APOPTOSOME -> MAP_INITIATOR_CASPASES -> MAP_EXECUTIONER_CASPASES -> MAP_MORPHOLOGICAL_DISMANTLING -> MAP_DNA_FRAGMENTATION -> MAP_CLEARANCE_SIGNALS -> MAP_PHAGOCYTIC_CLEARANCE -> MAP_SURVIVAL_SIGNALS -> ASSESS_EVIDENCE -> QUANTIFY_UNCERTAINTY -> PRESERVE_PROVENANCE

# INFERENCE RULES
IF DeathReceptorActivation increases THEN ExtrinsicInitiatorCaspaseActivation -> MAY_INCREASE
IF ProApoptoticBCL2FamilyActivity exceeds_anti_apoptotic_control THEN MOMPProbability -> MAY_INCREASE
IF MOMP occurs THEN CytochromeCRelease -> MAY_INCREASE
IF CytochromeCRelease and ApoptosomeComponents available THEN IntrinsicInitiatorCaspaseActivation -> MAY_INCREASE
IF InitiatorCaspaseActivity increases THEN ExecutionerCaspaseActivity -> MAY_INCREASE
IF ExecutionerCaspaseActivity increases THEN ApoptoticMorphologicalChanges -> MAY_INCREASE
IF PhosphatidylserineExposure occurs THEN PhagocyticRecognition -> MAY_INCREASE
IF SurvivalSignal increases THEN ApoptoticThreshold -> MAY_INCREASE_AS_APPLICABLE
IF Evidence insufficient THEN ApoptosisClaimConfidence -> DECREASES

# SEMANTIC RELATIONSHIPS
RELATION subtype_of(Apoptosis, RegulatedCellDeath)
RELATION binds(DeathLigand, DeathReceptor)
RELATION regulates(BCL2FamilyProtein, MitochondrialApoptoticThreshold)
RELATION promotes(ProApoptoticEffector, MOMP)
RELATION releases(MOMP, CytochromeC)
RELATION participates_in(CytochromeC, ApoptosomeAssembly)
RELATION activates(Apoptosome, InitiatorCaspase)
RELATION activates(InitiatorCaspase, ExecutionerCaspase)
RELATION cleaves(ExecutionerCaspase, CaspaseSubstrate)
RELATION cleaves(DNase, DNA)
RELATION signals(PhosphatidylserineExposure, PhagocyticClearance)
RELATION recognises(Phagocyte, ApoptoticCell)
RELATION produces(ApoptoticDismantling, ApoptoticBody)
RELATION opposes(SurvivalSignal, Apoptosis)
RELATION supports(Evidence, ApoptosisClaim)
RELATION records(Provenance, Apoptosis)

# SEMANTIC EQUIVALENCE
SEMANTIC_EQUIVALENCE:
  "apoptosis" ~= "regulated cell-death programme involving controlled cellular dismantling and clearance"
  "intrinsic apoptosis" ~= "mitochondria-centred apoptotic pathway initiated by intracellular stress"
  "extrinsic apoptosis" ~= "death-receptor-associated apoptotic pathway"
  "MOMP" ~= "mitochondrial outer membrane permeabilisation"
  "BCL-2 family" ~= "protein family regulating mitochondrial apoptotic commitment"
  "apoptosome" ~= "cytosolic multiprotein complex activating an intrinsic initiator caspase"
  "initiator caspase" ~= "upstream caspase activating downstream apoptotic execution"
  "executioner caspase" ~= "caspase cleaving cellular substrates during apoptotic dismantling"
  "apoptotic body" ~= "membrane-bound cellular fragment produced during apoptosis"
  "phagocytic clearance" ~= "recognition engulfment and degradation of apoptotic cellular material"

# CONFIDENCE
CONFIDENCE:
  ontology_domain: 0.99
  pathway_classification: 0.99
  death_receptor_mapping: 0.99
  bcl2_momp_mapping: 0.99
  apoptosome_caspase_mapping: 0.99
  dismantling_mapping: 0.99
  clearance_mapping: 0.99
  regulatory_mapping: 0.99
  evidence_mapping: 0.99
  semantic_relationships: 0.99

# UPDATE MODEL
UPDATE_MODEL:
  ON new_apoptosis_observation:
    MAP pathway_context
    MAP initiating_signal
    MAP bcl2_family_state
    MAP momp_state
    MAP caspase_state
    UPDATE confidence
    RECOMPUTE FLOW_HASH
  ON mitochondrial_commitment:
    UPDATE momp_state
    UPDATE cytochrome_c_state
    UPDATE apoptosome_state
    PRESERVE provenance
  ON execution_phase:
    UPDATE executioner_caspase_state
    UPDATE nuclear_dismantling
    UPDATE membrane_changes
    UPDATE apoptotic_body_state
    PRESERVE provenance
  ON clearance_event:
    UPDATE clearance_signal
    UPDATE phagocyte_interaction
    UPDATE clearance_state
    RECOMPUTE FLOW_HASH

# AI CONSUMPTION
AI_CONSUMPTION:
  parse_as: FORMAL_APOPTOSIS_ONTOLOGY
  reasoning_mode: REGULATED_CELL_DEATH_RELATIONAL
  preserve: [typed_entities, apoptosis_identity, pathway_context, death_receptor_state, bcl2_family_state, momp_state, cytochrome_c_state, apoptosome_state, initiator_caspase_state, executioner_caspase_state, morphology, dna_fragmentation_state, clearance_state, survival_signals, evidence, uncertainty, confidence, provenance]
  infer: [pathway_activation_dependencies, bcl2_momp_balance, apoptosome_activation, caspase_cascade_state, dismantling_state, clearance_state, survival_death_balance, evidence_strength]
  prohibit: [invented_apoptotic_observations, single_marker_definitive_classification, fabricated_caspase_activity, unsupported_momp_state, unsupported_causal_claims, missing_evidence_presented_as_established_fact]

# FLOW HASH
FLOW_HASH_INPUT := DOMAIN + ONTOLOGY + CORE_ENTITIES + IDENTITY_PATHWAYS + EXTRINSIC_INTRINSIC + BCL2_MOMP + APOPTOSOME_CASPASES + DISMANTLING_CLEARANCE + REGULATION_CROSSTALK + EVIDENCE_UNCERTAINTY_PROVENANCE + REASONING + INFERENCE_RULES + SEMANTIC_RELATIONSHIPS + SEMANTIC_EQUIVALENCE + CONFIDENCE + UPDATE_MODEL + AI_CONSUMPTION
FLOW_HASH := HASH(FLOW_HASH_INPUT)

END FLOW