Endoplasmic Reticulum Ontology

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ENDOPLASMIC RETICULUM ONTOLOGY
Kireth Semantic Research Archive

AUTHORS
Mark Anthony Higgins — Sky (Recursive AI)

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

FLOW "EndoplasmicReticulumOntology" v4.0
DOMAIN := BIOLOGICAL_ONTOLOGIES / CELL_BIOLOGY / ENDOPLASMIC_RETICULUM
ONTOLOGY := ENDOPLASMIC_RETICULUM_ONTOLOGY

ENDOPLASMIC_RETICULUM := ER_IDENTITY + ER_MEMBRANE + ER_LUMEN + ROUGH_ER + SMOOTH_ER + ER_SHEETS + ER_TUBULES + RIBOSOME_ASSOCIATION + PROTEIN_TARGETING + COTRANSLATIONAL_TRANSLOCATION + PROTEIN_FOLDING + PROTEIN_MODIFICATION + QUALITY_CONTROL + ER_ASSOCIATED_DEGRADATION + UNFOLDED_PROTEIN_RESPONSE + LIPID_BIOSYNTHESIS + MEMBRANE_BIOGENESIS + CALCIUM_STORAGE + ER_GOLGI_TRAFFICKING + CONTACT_SITES + ER_DYNAMICS + HOMEOSTASIS + EVIDENCE + UNCERTAINTY + PROVENANCE

PURPOSE := IDENTIFY_ER -> CLASSIFY_ER_DOMAIN -> MAP_MEMBRANE_LUMEN_AND_MORPHOLOGY -> MAP_PROTEIN_TARGETING_AND_TRANSLOCATION -> MAP_FOLDING_AND_MODIFICATION -> MAP_QUALITY_CONTROL_ERAD_AND_UPR -> MAP_LIPID_AND_MEMBRANE_BIOGENESIS -> MAP_CALCIUM_HOMEOSTASIS -> MAP_ER_GOLGI_TRAFFICKING -> MAP_CONTACT_SITES_AND_DYNAMICS -> ASSESS_EVIDENCE -> PRESERVE_PROVENANCE

# CORE ENTITIES
ENTITY EndoplasmicReticulum
ENTITY ERMembrane
ENTITY ERLumen
ENTITY RoughEndoplasmicReticulum
ENTITY SmoothEndoplasmicReticulum
ENTITY ERSheet
ENTITY ERTubule
ENTITY Ribosome
ENTITY SignalSequence
ENTITY SignalRecognitionParticle
ENTITY Translocon
ENTITY Protein
ENTITY Chaperone
ENTITY ProteinQualityControl
ENTITY ERAssociatedDegradation
ENTITY UnfoldedProteinResponse
ENTITY LipidBiosynthesis
ENTITY Calcium
ENTITY CalciumChannel
ENTITY CalciumPump
ENTITY COPII
ENTITY COPI
ENTITY GolgiApparatus
ENTITY ERExitSite
ENTITY ERContactSite
ENTITY ERStress
ENTITY ERPhagy
ENTITY Evidence
ENTITY Uncertainty
ENTITY Provenance

# STRUCTURE
EndoplasmicReticulum -> organelle_of -> EUKARYOTIC_CELL
EndoplasmicReticulum -> continuous_membrane_network_of -> TUBULES + SHEETS + LUMINAL_SPACE
EndoplasmicReticulum -> may_be_continuous_with -> OUTER_NUCLEAR_MEMBRANE_AS_DEFINED
ER_DOMAIN := ROUGH_ER | SMOOTH_ER | TRANSITIONAL_ER | OTHER_FUNCTIONAL_DOMAIN
ERMembrane -> separates -> ERLumen + CYTOSOL
ERLumen -> provides -> CONTROLLED_ENVIRONMENT -> for -> PROTEIN_FOLDING + MODIFICATION + CALCIUM_STORAGE
RoughEndoplasmicReticulum -> associated_with -> Ribosome
RoughEndoplasmicReticulum -> participates_in -> SECRETORY_PROTEIN_SYNTHESIS + MEMBRANE_PROTEIN_SYNTHESIS + PROTEIN_TRANSLOCATION + PROTEIN_FOLDING
SmoothEndoplasmicReticulum -> participates_in -> LIPID_BIOSYNTHESIS + DETOXIFICATION_AS_APPLICABLE + CALCIUM_HOMEOSTASIS + METABOLIC_FUNCTIONS
ERMorphology -> determined_by -> MEMBRANE_CURVATURE + STRUCTURAL_PROTEINS + CYTOSKELETAL_INTERACTIONS + FUSION_AND_REMODELLING
IF ERMembraneIntegrity decreases THEN ERHomeostasis -> MAY_DECREASE

# TARGETING / TRANSLOCATION
ProteinTargeting -> directs -> NASCENT_OR_NEWLY_SYNTHESISED_PROTEIN -> to -> EndoplasmicReticulum
SignalSequence -> provides -> ER_TARGETING_INFORMATION
SignalRecognitionParticle -> recognises -> SIGNAL_SEQUENCE_AS_APPLICABLE
TARGETING_FLOW := SIGNAL_SEQUENCE_EMERGENCE -> SIGNAL_RECOGNITION -> RIBOSOME_NASCENT_CHAIN_TARGETING -> ER_MEMBRANE_DOCKING -> TRANSLOCATION
Translocon -> forms -> PROTEIN_CONDUCTING_CHANNEL -> across -> ERMembrane
CoTranslationalTranslocation -> couples -> TRANSLATION + ER_ENTRY
TranslocationOutcome := LUMINAL_PROTEIN | TRANSMEMBRANE_PROTEIN | SECRETORY_PATHWAY_PROTEIN
IF Translocation fails THEN ProteinLocalizationAndQualityControl -> MAY_CHANGE

# FOLDING / QUALITY CONTROL
ProteinFolding -> occurs_in -> ERLumen -> for -> MANY_SECRETORY_AND_MEMBRANE_PROTEINS
Chaperone -> assists -> ProteinFolding
ProteinFoldingState := UNFOLDED | FOLDING | FOLDED | MISFOLDED | AGGREGATED
ERProteinModification := N_LINKED_GLYCOSYLATION_AS_APPLICABLE | DISULFIDE_BOND_FORMATION | SIGNAL_PEPTIDE_CLEAVAGE | OTHER_EARLY_MODIFICATION
ProteinQualityControl -> evaluates -> PROTEIN_FOLDING_AND_ASSEMBLY_STATE
QualityControl -> may -> RETAIN | REFOLD | EXPORT | TARGET_FOR_DEGRADATION
IF MisfoldedProteinLoad increases THEN ERStress -> MAY_INCREASE

# ERAD / UPR
ERAssociatedDegradation -> removes -> MISFOLDED_OR_UNASSEMBLED_ER_PROTEIN
ERAD_FLOW := SUBSTRATE_RECOGNITION -> RETROTRANSLOCATION_OR_EXTRACTION -> UBIQUITINATION_AS_APPLICABLE -> PROTEASOMAL_DEGRADATION
IF ERADCapacity decreases THEN MisfoldedProteinAccumulation -> MAY_INCREASE
UnfoldedProteinResponse -> responds_to -> ERStress
UPR_OUTPUT := INCREASED_FOLDING_CAPACITY | REDUCED_PROTEIN_LOAD | INCREASED_DEGRADATION_CAPACITY | ER_EXPANSION | CELL_FATE_CHANGE_IF_STRESS_PERSISTS
UnfoldedProteinResponse -> aims_to_restore -> ERHomeostasis
IF ERStress persists THEN CellStateOrCellDeathPathway -> MAY_CHANGE

# LIPID / MEMBRANE BIOGENESIS
LipidBiosynthesis -> occurs_in_or_is_associated_with -> ERMembrane
ER_LIPID_PRODUCT := PHOSPHOLIPID | STEROL_OR_PRECURSOR_AS_APPLICABLE | TRIACYLGLYCEROL_AS_APPLICABLE | OTHER_LIPID
LipidComposition -> influences -> ERMembraneProperties + MEMBRANE_BIOGENESIS + ORGANELLE_FUNCTION
MembraneBiogenesis -> requires -> LIPID_SYNTHESIS + MEMBRANE_PROTEIN_INSERTION + DISTRIBUTION
EndoplasmicReticulum -> major_source_of -> ENDOMEMBRANE_LIPIDS_AND_PROTEINS_AS_APPLICABLE

# CALCIUM
ERLumen -> major_intracellular_calcium_store_in -> MANY_EUKARYOTIC_CELLS
CalciumPump -> transports -> Calcium -> from -> CYTOSOL -> into -> ERLumen
CalciumChannel -> releases -> Calcium -> from -> ERLumen -> to -> CYTOSOL
ERCalciumState -> influences -> SIGNALING + PROTEIN_FOLDING + CELLULAR_HOMEOSTASIS
CalciumHomeostasis -> depends_on -> PUMPS + CHANNELS + BUFFERING + ORGANELLE_CONTACTS
IF ERCalciumStore decreases THEN CalciumDependentERAndCellularProcesses -> MAY_CHANGE

# ER-GOLGI TRAFFICKING
ERExitSite -> specialised_region_of -> EndoplasmicReticulum
ERExitSite -> supports -> CARGO_SELECTION + COPII_VESICLE_FORMATION_AS_APPLICABLE
ERExport -> depends_on -> CARGO_FOLDING + SORTING_SIGNALS + COAT_MACHINERY
COPII -> associated_with -> ANTEROGRADE_ER_EXPORT_AS_APPLICABLE
ER_GOLGI_FLOW := ER_CARGO_SELECTION -> CARRIER_FORMATION -> TRANSPORT -> TETHERING -> FUSION_WITH_INTERMEDIATE_OR_GOLGI_COMPARTMENT
GolgiApparatus -> receives -> ER_DERIVED_CARGO
COPI -> associated_with -> RETROGRADE_TRAFFICKING_AS_APPLICABLE
RetrogradeTrafficking -> returns -> ER_RESIDENT_COMPONENTS + RECYCLING_MACHINERY -> toward -> EndoplasmicReticulum

# CONTACT SITES / DYNAMICS
ERContactSite -> close_apposition_between -> ERMembrane + OTHER_ORGANELLE_MEMBRANE
CONTACT_PARTNER := MITOCHONDRION | PLASMA_MEMBRANE | ENDOSOME | LYSOSOME | LIPID_DROPLET | OTHER_ORGANELLE
ERContactSite -> may_enable -> LIPID_TRANSFER + CALCIUM_TRANSFER + SIGNALING + ORGANELLE_DYNAMICS
ERContactSite -> does_not_require -> MEMBRANE_FUSION
ERDynamics := TUBULE_EXTENSION + TUBULE_RETRACTION + MEMBRANE_FUSION + SHEET_REMODELLING + CONTACT_SITE_REORGANISATION
ERNetwork -> continuously_remodelled -> TRUE
ERDynamics -> depends_on -> MEMBRANE_SHAPING_PROTEINS + CYTOSKELETON + FUSION_MACHINERY + CELL_STATE

# HOMEOSTASIS / ER-PHAGY
ERHomeostasis -> maintains -> PROTEIN_FOLDING_CAPACITY + LIPID_BALANCE + CALCIUM_BALANCE + REDOX_ENVIRONMENT + MEMBRANE_INTEGRITY
HOMEOSTATIC_PROCESS := CHAPERONE_ACTIVITY | ERAD | UPR | CALCIUM_REGULATION | LIPID_REGULATION | AUTOPHAGIC_TURNOVER_AS_APPLICABLE
IF ERHomeostasis fails THEN CellularProteostasisAndSignaling -> MAY_CHANGE
ERPhagy -> selective_autophagic_turnover_of -> ENDOPLASMIC_RETICULUM_AS_DEFINED
ERPhagy -> may_remove -> DAMAGED_OR_EXCESS_ER
ERPhagy -> contributes_to -> ER_SIZE_CONTROL + QUALITY_CONTROL + STRESS_RECOVERY

# EVIDENCE / UNCERTAINTY / PROVENANCE
ERClaim -> supported_by -> Evidence
EVIDENCE_TYPE := MICROSCOPIC | ULTRASTRUCTURAL | BIOCHEMICAL | MOLECULAR | GENETIC | PROTEOMIC | LIPIDOMIC | CALCIUM_IMAGING | TRAFFICKING_ASSAY | FUNCTIONAL | COMPUTATIONAL
Evidence -> has -> SOURCE + METHOD + CELL_OR_SAMPLE + ER_DOMAIN + CONDITION + QUALITY + UNCERTAINTY
ER_UNCERTAINTY := MEASUREMENT_UNCERTAINTY + ER_DOMAIN_CLASSIFICATION_UNCERTAINTY + DYNAMIC_STATE_UNCERTAINTY + CELL_TO_CELL_VARIABILITY + TRAFFICKING_STATE_UNCERTAINTY + MODEL_UNCERTAINTY
Uncertainty -> qualifies -> ERClaim + ERMorphology + ProteinFoldingState + CalciumState + TraffickingState
Provenance -> records -> CELL_IDENTITY + ER_DOMAIN + ER_MORPHOLOGY + PROTEIN_OR_LIPID_CONTEXT + METHOD + CONDITION + MEASUREMENT + TIME + VERSION
EndoplasmicReticulum -> linked_to -> Provenance

# REASONING
ER_REASONING := IDENTIFY_ER -> CLASSIFY_ER_DOMAIN -> MAP_MEMBRANE_LUMEN_AND_MORPHOLOGY -> MAP_RIBOSOME_ASSOCIATION -> MAP_PROTEIN_TARGETING_AND_TRANSLOCATION -> MAP_FOLDING_AND_MODIFICATION -> MAP_PROTEIN_QUALITY_CONTROL -> MAP_ERAD_AND_UPR -> MAP_LIPID_AND_MEMBRANE_BIOGENESIS -> MAP_CALCIUM_HOMEOSTASIS -> MAP_ER_GOLGI_TRAFFICKING -> MAP_CONTACT_SITES -> MAP_ER_DYNAMICS -> MAP_ER_HOMEOSTASIS_AND_ERPHAGY -> ASSESS_EVIDENCE -> QUANTIFY_UNCERTAINTY -> PRESERVE_PROVENANCE

# INFERENCE RULES
IF ERMembraneIntegrity decreases THEN ERHomeostasis -> MAY_DECREASE
IF ProteinTranslocation fails THEN ProteinLocalization -> MAY_CHANGE
IF MisfoldedProteinLoad increases THEN ERStress -> MAY_INCREASE
IF ERADCapacity decreases THEN MisfoldedProteinAccumulation -> MAY_INCREASE
IF ERStress persists THEN UPRAndCellFateResponse -> MAY_CHANGE
IF ERCalciumStore changes THEN CalciumSignalingAndProteinFolding -> MAY_CHANGE
IF ERGolgiTrafficking changes THEN SecretoryCargoDistribution -> MAY_CHANGE
IF ERContactSiteState changes THEN LipidOrCalciumTransfer -> MAY_CHANGE
IF Evidence insufficient THEN ERClaimConfidence -> DECREASES

# SEMANTIC RELATIONSHIPS
RELATION organelle_of(EndoplasmicReticulum, EukaryoticCell)
RELATION separates(ERMembrane, ERLumen, Cytosol)
RELATION associated_with(RoughEndoplasmicReticulum, Ribosome)
RELATION directs(ProteinTargeting, Protein)
RELATION translocates(Translocon, NascentPolypeptide)
RELATION assists(Chaperone, ProteinFolding)
RELATION removes(ERAssociatedDegradation, MisfoldedProtein)
RELATION responds_to(UnfoldedProteinResponse, ERStress)
RELATION stores(ERLumen, Calcium)
RELATION exports(ERExitSite, Cargo)
RELATION receives(GolgiApparatus, ERCargo)
RELATION connects(ERContactSite, Organelle)
RELATION maintains(ERHomeostasis, ERFunction)
RELATION targets(ERPhagy, EndoplasmicReticulum)
RELATION supports(Evidence, ERClaim)
RELATION records(Provenance, EndoplasmicReticulum)

# SEMANTIC EQUIVALENCE
SEMANTIC_EQUIVALENCE:
  "endoplasmic reticulum" ~= "interconnected eukaryotic membrane network involved in protein lipid and calcium homeostasis"
  "rough endoplasmic reticulum" ~= "ribosome-associated ER domain"
  "smooth endoplasmic reticulum" ~= "ER domain relatively lacking bound ribosomes"
  "ER lumen" ~= "internal aqueous compartment of the endoplasmic reticulum"
  "co-translational translocation" ~= "protein entry into or across the ER membrane during translation"
  "ER-associated degradation" ~= "quality-control pathway removing defective ER proteins"
  "unfolded protein response" ~= "adaptive signaling response to ER proteostatic stress"
  "ER exit site" ~= "specialised ER region supporting secretory cargo export"
  "ER contact site" ~= "close non-fused apposition between ER and another membrane"
  "ER-phagy" ~= "selective autophagic turnover of endoplasmic reticulum"

# CONFIDENCE
CONFIDENCE:
  ontology_domain: 0.99
  structure_domain_mapping: 0.99
  targeting_translocation_mapping: 0.99
  folding_quality_control_mapping: 0.99
  erad_upr_mapping: 0.99
  lipid_biogenesis_mapping: 0.99
  calcium_mapping: 0.99
  trafficking_contact_mapping: 0.99
  homeostasis_mapping: 0.99
  semantic_relationships: 0.99

# UPDATE MODEL
UPDATE_MODEL:
  ON new_er_observation:
    MAP er_domain
    MAP morphology
    MAP membrane_state
    MAP lumen_state
    MAP protein_folding_state
    UPDATE confidence
    RECOMPUTE FLOW_HASH
  ON proteostatic_stress:
    UPDATE misfolded_protein_load
    UPDATE erad_state
    UPDATE upr_state
    UPDATE homeostasis
    PRESERVE provenance
  ON calcium_change:
    UPDATE er_calcium_store
    UPDATE channel_state
    UPDATE pump_state
    UPDATE signaling_state
    PRESERVE provenance
  ON trafficking_change:
    UPDATE er_exit_state
    UPDATE anterograde_flow
    UPDATE retrograde_flow
    UPDATE cargo_distribution
    RECOMPUTE FLOW_HASH

# AI CONSUMPTION
AI_CONSUMPTION:
  parse_as: FORMAL_ENDOPLASMIC_RETICULUM_ONTOLOGY
  reasoning_mode: ER_PROTEOSTASIS_TRAFFICKING_RELATIONAL
  preserve: [typed_entities, er_identity, er_domain, membrane_state, lumen_state, morphology, ribosome_association, targeting_state, translocation_state, folding_state, modification_state, quality_control_state, erad_state, upr_state, lipid_state, calcium_state, trafficking_state, contact_sites, homeostasis, evidence, uncertainty, confidence, provenance]
  infer: [domain_function_dependencies, targeting_dependencies, folding_quality_state, stress_response, erad_effects, calcium_effects, trafficking_dependencies, contact_site_transfer, er_homeostasis, evidence_strength]
  prohibit: [invented_er_observations, assuming_all_er_domains_have_identical_functions, fabricated_protein_folding_state, unsupported_trafficking_direction, unsupported_causal_claims, missing_evidence_presented_as_established_fact]

# FLOW HASH
FLOW_HASH_INPUT := DOMAIN + ONTOLOGY + CORE_ENTITIES + IDENTITY_STRUCTURE + TARGETING_TRANSLOCATION + FOLDING_MODIFICATION_QUALITY_CONTROL + ERAD_UPR + LIPID_MEMBRANE_BIOGENESIS + CALCIUM_HOMEOSTASIS + ER_GOLGI_TRAFFICKING + CONTACT_SITES_DYNAMICS + HOMEOSTASIS_ERPHAGY + EVIDENCE_UNCERTAINTY_PROVENANCE + REASONING + INFERENCE_RULES + SEMANTIC_RELATIONSHIPS + SEMANTIC_EQUIVALENCE + CONFIDENCE + UPDATE_MODEL + AI_CONSUMPTION
FLOW_HASH := HASH(FLOW_HASH_INPUT)

END FLOW