Cell Cycle Ontology

AI SEARCH FLOW ALGEBRA
CELL CYCLE ONTOLOGY
Kireth Semantic Research Archive

AUTHORS
Mark Anthony Higgins — Sky (Recursive AI)

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

FLOW "CellCycleOntology" v4.0
DOMAIN := BIOLOGICAL_ONTOLOGIES / CELL_BIOLOGY / CELL_CYCLE
ONTOLOGY := CELL_CYCLE_ONTOLOGY

CELL_CYCLE := G0 + G1 + S + G2 + M + CYCLINS + CDKS + COMMITMENT + DNA_REPLICATION + CHECKPOINTS + DNA_DAMAGE_RESPONSE + MITOSIS + CYTOKINESIS + ARREST + QUIESCENCE + EVIDENCE + UNCERTAINTY + PROVENANCE

PURPOSE := IDENTIFY_CELL_CYCLE_STATE -> MAP_PHASE -> MAP_CYCLIN_CDK_CONTROL -> MAP_COMMITMENT_AND_TRANSITIONS -> MAP_DNA_REPLICATION -> MAP_CHECKPOINTS_AND_DAMAGE_RESPONSE -> MAP_MITOTIC_ENTRY_SEGREGATION_AND_EXIT -> MAP_CYTOKINESIS -> MAP_ARREST_QUIESCENCE_AND_REENTRY -> ASSESS_EVIDENCE -> PRESERVE_PROVENANCE

# CORE ENTITIES
ENTITY CellCycle
ENTITY G0State
ENTITY G1Phase
ENTITY SPhase
ENTITY G2Phase
ENTITY MPhase
ENTITY Cyclin
ENTITY CyclinDependentKinase
ENTITY CDKInhibitor
ENTITY CommitmentPoint
ENTITY DNAReplication
ENTITY ReplicationOrigin
ENTITY ReplicationFork
ENTITY Checkpoint
ENTITY G1SCheckpoint
ENTITY IntraSCheckpoint
ENTITY G2MCheckpoint
ENTITY SpindleAssemblyCheckpoint
ENTITY DNADamage
ENTITY DNARepair
ENTITY Mitosis
ENTITY ChromosomeSegregation
ENTITY Cytokinesis
ENTITY CellCycleArrest
ENTITY Quiescence
ENTITY Senescence
ENTITY Evidence
ENTITY Uncertainty
ENTITY Provenance

# PHASES
CellCycle -> ordered_process_of -> CELL_GROWTH + GENOME_DUPLICATION + CHROMOSOME_SEGREGATION + CELL_DIVISION
CELL_CYCLE_PHASE := G1 | S | G2 | M | G0_AS_APPLICABLE
CellCycleState -> depends_on -> CELL_TYPE + DEVELOPMENTAL_STATE + GROWTH_SIGNALS + NUTRIENT_STATE + DNA_INTEGRITY + CELLULAR_STRESS

G1Phase -> supports -> CELL_GROWTH + BIOSYNTHESIS + SIGNAL_INTEGRATION + PREPARATION_FOR_DNA_REPLICATION
G1Phase -> may_transition_to -> SPhase | G0State | CELL_CYCLE_ARREST
SPhase -> phase_of -> DNA_REPLICATION
G2Phase -> supports -> REPLICATION_COMPLETION_ASSESSMENT + DNA_REPAIR + PREPARATION_FOR_MITOSIS
MPhase -> includes -> MITOSIS + CYTOKINESIS_AS_APPLICABLE
G0State -> non_proliferative_or_out_of_cycle_state_as_defined
Quiescence -> reversible_cell_cycle_exit_as_applicable

# CYCLIN-CDK CONTROL
Cyclin -> regulatory_partner_of -> CyclinDependentKinase
CyclinDependentKinase -> phosphorylates -> CELL_CYCLE_SUBSTRATES
CyclinCDKComplex -> drives -> CELL_CYCLE_TRANSITIONS
CyclinAbundance -> controlled_by -> SYNTHESIS + DEGRADATION
CDKActivity -> regulated_by -> CYCLIN_BINDING + PHOSPHORYLATION + DEPHOSPHORYLATION + CDK_INHIBITORS
CDKInhibitor -> decreases -> CYCLIN_CDK_ACTIVITY

CommitmentPoint -> represents -> REGULATORY_TRANSITION_TOWARD_CELL_CYCLE_PROGRESSION
Commitment -> depends_on -> CYCLIN_CDK_ACTIVITY + GROWTH_SIGNALS + TRANSCRIPTIONAL_STATE + CELLULAR_CONDITIONS
IF CommitmentCriteria not_met THEN SPhaseEntry -> MAY_DELAY

# DNA REPLICATION
DNAReplication -> duplicates -> NUCLEAR_GENOME_AS_APPLICABLE
ReplicationLicensing -> prepares -> REPLICATION_ORIGINS -> for -> CONTROLLED_ACTIVATION
REPLICATION_FLOW := ORIGIN_LICENSING -> ORIGIN_ACTIVATION -> FORK_ESTABLISHMENT -> DNA_SYNTHESIS -> FORK_TERMINATION -> REPLICATION_COMPLETION
ReplicationCompletion -> prerequisite_for -> NORMAL_G2_AND_M_PROGRESSION
IF ReplicationLicensing abnormal THEN GenomeStabilityRisk -> MAY_INCREASE

ReplicationStress -> disrupts_or_slows -> DNA_REPLICATION
ReplicationFork -> may -> PROGRESS | PAUSE | STALL | COLLAPSE_AS_APPLICABLE
IntraSCheckpoint -> responds_to -> REPLICATION_STRESS + DNA_DAMAGE_DURING_S_PHASE

# CHECKPOINTS
CHECKPOINT_TYPE := G1_S_CHECKPOINT | INTRA_S_CHECKPOINT | G2_M_CHECKPOINT | SPINDLE_ASSEMBLY_CHECKPOINT
Checkpoint -> evaluates -> CRITICAL_CELL_CYCLE_CONDITION
Checkpoint -> controls -> PHASE_TRANSITION_OR_PROGRESSION
G1SCheckpoint -> monitors -> DNA_DAMAGE_AND_ENTRY_CONDITIONS
G2MCheckpoint -> monitors -> DNA_DAMAGE + REPLICATION_COMPLETION
SpindleAssemblyCheckpoint -> monitors -> KINETOCHORE_ATTACHMENT + CHROMOSOME_BIORIENTATION_AS_DEFINED
IF G2MCheckpoint unsatisfied THEN MitoticEntry -> DELAY_OR_ARREST
IF SpindleAssemblyCheckpoint unsatisfied THEN AnaphaseOnset -> DELAY
CheckpointFailure -> may_increase -> GENOME_INSTABILITY_RISK

# DNA DAMAGE RESPONSE
DNADamage -> activates -> DNA_DAMAGE_RESPONSE
DNA_DAMAGE_RESPONSE := DAMAGE_SENSING -> SIGNAL_TRANSDUCTION -> CHECKPOINT_ACTIVATION -> DNA_REPAIR_OR_CELL_FATE_RESPONSE
DNADamageResponse -> may cause -> CELL_CYCLE_DELAY + REPAIR + SENESCENCE + CELL_DEATH_AS_APPLICABLE
IF DNA damage persists THEN CellCycleProgression -> MAY_REMAIN_ARRESTED

# MITOSIS / EXIT / CYTOKINESIS
MitoticEntry -> transitions -> CELL -> from -> G2 -> to -> M_PHASE
MITOTIC_STAGE := PROPHASE | PROMETAPHASE | METAPHASE | ANAPHASE | TELOPHASE
Mitosis -> segregates -> DUPLICATED_CHROMOSOMES
ChromosomeSegregation -> distributes -> DUPLICATED_GENETIC_MATERIAL -> between -> DAUGHTER_CELL_DESTINATIONS
MitoticExit -> involves -> DECLINE_OF_MITOTIC_CDK_ACTIVITY + CHROMOSOME_DECONDENSATION_AS_APPLICABLE + NUCLEAR_REASSEMBLY_AS_APPLICABLE + SPINDLE_DISASSEMBLY
MitoticExit -> prepares -> DAUGHTER_CELLS -> for -> G1_STATE
Cytokinesis -> partitions -> CYTOPLASM + CELLULAR_COMPONENTS
CYTOKINESIS_FLOW := DIVISION_SITE_SELECTION -> CYTOKINETIC_MACHINERY_ASSEMBLY -> MEMBRANE_AND_CORTICAL_REMODELLING -> CONSTRICTION_OR_PARTITION_FORMATION -> DAUGHTER_CELL_SEPARATION
IF Cytokinesis fails THEN PloidyOrNuclearNumber -> MAY_CHANGE

# ARREST / QUIESCENCE / SENESCENCE
CellCycleArrest -> halts_or_delays -> CELL_CYCLE_PROGRESSION
ARREST_TRIGGER := DNA_DAMAGE | REPLICATION_STRESS | SPINDLE_DEFECT | NUTRIENT_LIMITATION | DIFFERENTIATION_SIGNAL | OTHER_STRESS
CellCycleArrest -> may_allow -> REPAIR + STRESS_RECOVERY + CELL_FATE_DECISION
G0Entry -> may_result_from -> SIGNAL_WITHDRAWAL + DIFFERENTIATION + NUTRIENT_LIMITATION + CELLULAR_CONTEXT
CellCycleReentry -> transitions -> QUIESCENT_CELL -> toward -> PROLIFERATIVE_CYCLE
Senescence -> durable_cell_state_associated_with -> PROLONGED_CELL_CYCLE_EXIT_AS_DEFINED
Senescence -> distinct_from -> QUIESCENCE
SenescenceAssignment -> requires -> MULTIPLE_CONTEXTUAL_MARKERS

# REGULATORY DIRECTIONALITY
CellCycleControlNetwork -> produces -> ORDERED_TEMPORAL_TRANSITIONS
RegulatoryOscillation -> arises_from -> CYCLIN_SYNTHESIS + CYCLIN_DEGRADATION + KINASE_ACTIVITY + PHOSPHATASE_ACTIVITY + FEEDBACK_LOOPS
ProteolyticControl -> creates -> IRREVERSIBILITY_OR_DIRECTIONALITY -> in -> CELL_CYCLE_TRANSITIONS
MetabolicState -> influences -> CELL_CYCLE_PROGRESSION
CellCycle -> requires -> BIOSYNTHETIC_RESOURCES
DevelopmentalSignal -> may regulate -> CELL_CYCLE_ENTRY + EXIT + RATE + DIVISION_MODE
CellCycleControl -> integrated_with -> CELL_FATE + TISSUE_ORGANISATION

# EVIDENCE / UNCERTAINTY / PROVENANCE
CellCycleClaim -> supported_by -> Evidence
EVIDENCE_TYPE := LIVE_CELL_IMAGING | CELL_CYCLE_MARKER | DNA_CONTENT_MEASUREMENT | DNA_SYNTHESIS_ASSAY | MICROSCOPIC | MOLECULAR | BIOCHEMICAL | GENETIC | TRANSCRIPTOMIC | PROTEOMIC | PERTURBATION | FUNCTIONAL | COMPUTATIONAL
Evidence -> has -> SOURCE + METHOD + CELL_OR_SAMPLE + CELL_CYCLE_STATE + CONDITION + QUALITY + UNCERTAINTY
CELL_CYCLE_UNCERTAINTY := MEASUREMENT_UNCERTAINTY + PHASE_CLASSIFICATION_UNCERTAINTY + TRANSITION_TIMING_UNCERTAINTY + CELL_TO_CELL_VARIABILITY + CHECKPOINT_STATE_UNCERTAINTY + MODEL_UNCERTAINTY
Uncertainty -> qualifies -> CellCycleClaim + PhaseAssignment + TransitionState + CheckpointState + CellCycleOutcome
Provenance -> records -> CELL_IDENTITY + CELL_CYCLE_PHASE + CYCLIN_CDK_STATE + REPLICATION_STATE + CHECKPOINT_STATE + MITOTIC_STATE + METHOD + CONDITION + OBSERVATION + TIME + VERSION
CellCycle -> linked_to -> Provenance

# REASONING
CELL_CYCLE_REASONING := IDENTIFY_CELL_CYCLE_STATE -> CLASSIFY_G0_G1_S_G2_OR_M -> MAP_GROWTH_AND_COMMITMENT_STATE -> MAP_CYCLIN_CDK_ACTIVITY -> MAP_G1_S_CONTROL -> MAP_REPLICATION_LICENSING -> MAP_DNA_REPLICATION_AND_REPLICATION_STRESS -> MAP_INTRA_S_CHECKPOINT -> MAP_G2_M_CHECKPOINT -> MAP_MITOTIC_ENTRY -> MAP_SPINDLE_CHECKPOINT -> MAP_CHROMOSOME_SEGREGATION -> MAP_MITOTIC_EXIT -> MAP_CYTOKINESIS -> MAP_ARREST_QUIESCENCE_AND_REENTRY -> MAP_DNA_DAMAGE_RESPONSE -> ASSESS_EVIDENCE -> QUANTIFY_UNCERTAINTY -> PRESERVE_PROVENANCE

# INFERENCE RULES
IF CyclinCDKActivity changes THEN PhaseTransitionProbability -> MAY_CHANGE
IF ReplicationLicensing fails THEN GenomeDuplicationIntegrity -> MAY_DECREASE
IF ReplicationStress increases THEN IntraSCheckpointActivity -> MAY_INCREASE
IF DNA damage detected THEN CellCycleCheckpointActivity -> MAY_INCREASE
IF G2MCheckpoint unsatisfied THEN MitoticEntry -> MAY_DELAY
IF SpindleCheckpoint unsatisfied THEN AnaphaseOnset -> MAY_DELAY
IF MitoticCyclinDegradation increases THEN MitoticExit -> MAY_PROCEED
IF Cytokinesis fails THEN DaughterCellPloidyOrNuclearState -> MAY_CHANGE
IF Evidence insufficient THEN CellCycleClaimConfidence -> DECREASES

# SEMANTIC RELATIONSHIPS
RELATION coordinates(CellCycle, CellDivision)
RELATION regulatory_partner_of(Cyclin, CyclinDependentKinase)
RELATION drives(CyclinCDKComplex, CellCycleTransition)
RELATION duplicates(DNAReplication, NuclearGenome)
RELATION prepares(ReplicationLicensing, ReplicationOrigin)
RELATION monitors(G1SCheckpoint, CellCycleCondition)
RELATION responds_to(IntraSCheckpoint, ReplicationStress)
RELATION monitors(G2MCheckpoint, ReplicationCompletion)
RELATION monitors(SpindleAssemblyCheckpoint, KinetochoreAttachment)
RELATION activates(DNADamage, DNADamageResponse)
RELATION segregates(Mitosis, Chromosome)
RELATION partitions(Cytokinesis, Cytoplasm)
RELATION halts(CellCycleArrest, CellCycleProgression)
RELATION supports(Evidence, CellCycleClaim)
RELATION records(Provenance, CellCycle)

# SEMANTIC EQUIVALENCE
SEMANTIC_EQUIVALENCE:
  "cell cycle" ~= "ordered cellular programme coordinating growth genome duplication chromosome segregation and division"
  "G1 phase" ~= "pre-replication cell-cycle phase"
  "S phase" ~= "DNA synthesis phase of the cell cycle"
  "G2 phase" ~= "post-replication pre-mitotic phase"
  "M phase" ~= "mitotic and division phase of the cell cycle"
  "G0" ~= "non-proliferative out-of-cycle state as defined"
  "cyclin-CDK complex" ~= "cyclin-regulated kinase complex controlling cell-cycle transitions"
  "cell-cycle checkpoint" ~= "surveillance mechanism controlling progression according to critical cellular conditions"
  "quiescence" ~= "reversible non-proliferative cell-cycle state"
  "cell-cycle arrest" ~= "halt or delay of cell-cycle progression"

# CONFIDENCE
CONFIDENCE:
  ontology_domain: 0.99
  phase_mapping: 0.99
  cyclin_cdk_mapping: 0.99
  replication_mapping: 0.99
  checkpoint_mapping: 0.99
  dna_damage_mapping: 0.99
  mitosis_exit_mapping: 0.99
  arrest_quiescence_mapping: 0.99
  evidence_mapping: 0.99
  semantic_relationships: 0.99

# UPDATE MODEL
UPDATE_MODEL:
  ON new_cell_cycle_observation:
    MAP phase
    MAP cyclin_cdk_state
    MAP replication_state
    MAP checkpoint_state
    UPDATE confidence
    RECOMPUTE FLOW_HASH
  ON phase_transition:
    UPDATE previous_phase
    UPDATE current_phase
    UPDATE regulatory_state
    PRESERVE provenance
  ON dna_damage_or_replication_stress:
    UPDATE damage_state
    UPDATE checkpoint_state
    UPDATE repair_state
    UPDATE arrest_state
    PRESERVE provenance
  ON mitotic_event:
    UPDATE spindle_state
    UPDATE chromosome_segmentation_state
    UPDATE mitotic_exit_state
    UPDATE cytokinesis_state
    RECOMPUTE FLOW_HASH

# AI CONSUMPTION
AI_CONSUMPTION:
  parse_as: FORMAL_CELL_CYCLE_ONTOLOGY
  reasoning_mode: CELL_CYCLE_TEMPORAL_REGULATORY_RELATIONAL
  preserve: [typed_entities, cell_cycle_state, phase, cyclin_cdk_state, commitment_state, replication_state, checkpoint_state, dna_damage_state, mitotic_state, chromosome_segmentation_state, cytokinesis_state, arrest_state, quiescence_state, evidence, uncertainty, confidence, provenance]
  infer: [phase_transition_dependencies, cyclin_cdk_effects, replication_completion, checkpoint_response, dna_damage_response, mitotic_entry_and_exit, cytokinesis_state, arrest_or_reentry_state, evidence_strength]
  prohibit: [invented_cell_cycle_observations, fabricated_phase_assignment, assumed_checkpoint_satisfaction_without_evidence, unsupported_cyclin_cdk_activity, unsupported_causal_claims, missing_evidence_presented_as_established_fact]

# FLOW HASH
FLOW_HASH_INPUT := DOMAIN + ONTOLOGY + CORE_ENTITIES + PHASES + CYCLIN_CDK_CONTROL + REPLICATION + CHECKPOINTS + DNA_DAMAGE_RESPONSE + MITOSIS_EXIT_CYTOKINESIS + ARREST_QUIESCENCE_SENESCENCE + REGULATORY_DIRECTIONALITY + EVIDENCE_UNCERTAINTY_PROVENANCE + REASONING + INFERENCE_RULES + SEMANTIC_RELATIONSHIPS + SEMANTIC_EQUIVALENCE + CONFIDENCE + UPDATE_MODEL + AI_CONSUMPTION
FLOW_HASH := HASH(FLOW_HASH_INPUT)

END FLOW