Gene Expression Ontology

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

flow "GeneExpressionOntology" v1.0

# ============================================================
# IDENTITY
# ============================================================

ENTITY GeneExpressionOntology {
    TYPE: BiologicalOntology
    DOMAIN: MolecularBiology
    SUBJECT: GeneExpression
    PURPOSE: FormalSemanticRepresentation
}

PAGE {
    TITLE: "Gene Expression Ontology"
    PARENT_DOMAIN: "Molecular Biology"
    CANONICAL_URL: "https://kirethresearch.org/booksai-core/ontologies/biological-ontologies/molecular-biology/gene-expression-ontology.html"
    AUTHORS: ["Mark Anthony Higgins", "Sky Recursive AI"]
}

# ============================================================
# CORE ENTITY MODEL
# ============================================================

PROCESS GeneExpression {
    INPUT: Gene
    PRODUCES: FunctionalGeneProduct
    MAY_INCLUDE: [
        Transcription,
        RNAProcessing,
        Translation,
        ProteinFolding,
        PostTranslationalModification
    ]
    REGULATED_BY: GeneExpressionRegulation
}

ENTITY Gene {
    IS_A: HereditaryInformationUnit
    PART_OF: Genome
    MAY_ENCODE: [FunctionalRNA, Protein]
}

ENTITY FunctionalGeneProduct {
    MAY_BE: [FunctionalRNA, Protein]
    DERIVED_FROM: Gene
    MAY_PERFORM: MolecularFunction
}

ENTITY ExpressionState {
    DESCRIBES: GeneExpression
    MAY_INCLUDE: [
        Active,
        Inactive,
        Upregulated,
        Downregulated,
        Constitutive,
        Inducible,
        Repressed
    ]
}

# ============================================================
# CENTRAL INFORMATION FLOW
# ============================================================

PROCESS Transcription {
    INPUT: DNA
    TEMPLATE: Gene
    CATALYSED_BY: RNA_Polymerase
    OUTPUT: RNA
}

PROCESS RNAProcessing {
    INPUT: PrimaryTranscript
    MAY_INCLUDE: [
        FivePrimeCapping,
        RNA_Splicing,
        Polyadenylation,
        RNAEditing
    ]
    OUTPUT: MatureRNA
}

PROCESS Translation {
    INPUT: mRNA
    EXECUTED_BY: Ribosome
    OUTPUT: Polypeptide
}

RULE ProteinCodingExpression {
    IF Gene.type == ProteinCodingGene
    THEN GeneExpression MAY_FOLLOW [
        Transcription,
        RNAProcessing,
        Translation
    ]
}

RULE NonCodingExpression {
    IF Gene.type == NonCodingGene
    THEN FunctionalGeneProduct MAY_BE RNA
    AND Translation IS_NOT_REQUIRED
}

# ============================================================
# TRANSCRIPTIONAL REGULATION
# ============================================================

PROCESS TranscriptionalRegulation {
    TARGET: Transcription
    MAY_USE: [
        Promoter,
        Enhancer,
        Silencer,
        TranscriptionFactor,
        ChromatinState,
        EpigeneticModification
    ]
}

ENTITY Promoter {
    IS_A: RegulatoryDNARegion
    ASSOCIATED_WITH: TranscriptionInitiation
}

ENTITY Enhancer {
    IS_A: RegulatoryDNARegion
    MAY_INCREASE: Transcription
}

ENTITY Silencer {
    IS_A: RegulatoryDNARegion
    MAY_DECREASE: Transcription
}

ENTITY TranscriptionFactor {
    IS_A: RegulatoryProtein
    BINDS_TO: RegulatoryDNARegion
    MAY_ACT_AS: [Activator, Repressor]
}

RULE TranscriptionActivation {
    IF Activator BINDS compatible_RegulatoryRegion
    THEN transcription_rate MAY_INCREASE
}

RULE TranscriptionRepression {
    IF Repressor BINDS compatible_RegulatoryRegion
    THEN transcription_rate MAY_DECREASE
}

# ============================================================
# EPIGENETIC REGULATION
# ============================================================

PROCESS EpigeneticRegulation {
    MODULATES: GeneExpression
    WITHOUT_REQUIRING: DNASequenceChange
    MAY_INCLUDE: [
        DNA_Methylation,
        HistoneModification,
        ChromatinRemodelling
    ]
}

ENTITY ChromatinState {
    MAY_BE: [Accessible, Compact]
    AFFECTS: DNAAccessibility
}

ENTITY DNA_Methylation {
    IS_A: EpigeneticModification
    MAY_AFFECT: Transcription
}

ENTITY HistoneModification {
    IS_A: EpigeneticModification
    MAY_AFFECT: ChromatinState
}

RULE AccessibilityRule {
    IF ChromatinState == Accessible
    THEN transcriptional_access MAY_INCREASE
}

# ============================================================
# POST-TRANSCRIPTIONAL REGULATION
# ============================================================

PROCESS PostTranscriptionalRegulation {
    TARGET: RNA
    MAY_AFFECT: [
        RNAProcessing,
        RNAStability,
        RNAExport,
        RNAEditing,
        TranslationEfficiency
    ]
}

ENTITY AlternativeSplicing {
    IS_A: RNAProcessing
    PRODUCES: AlternativeTranscriptIsoforms
}

ENTITY RNA_BindingProtein {
    BINDS: RNA
    MAY_REGULATE: [
        Splicing,
        Stability,
        Localization,
        Translation
    ]
}

ENTITY RegulatoryRNA {
    MAY_INCLUDE: [miRNA, siRNA, lncRNA]
    MAY_MODULATE: GeneExpression
}

RULE RNAStabilityRule {
    IF RNAStability INCREASES
    THEN steady_state_RNA_abundance MAY_INCREASE
    subject_to_transcription_rate()
}

# ============================================================
# TRANSLATIONAL REGULATION
# ============================================================

PROCESS TranslationalRegulation {
    TARGET: Translation
    MAY_AFFECT: [
        RibosomeRecruitment,
        Initiation,
        Elongation,
        Termination
    ]
}

ENTITY TranslationFactor {
    PARTICIPATES_IN: Translation
    MAY_REGULATE: TranslationEfficiency
}

RULE TranslationEfficiencyRule {
    IF ribosome_recruitment INCREASES
       AND other_constraints ARE_UNCHANGED
    THEN protein_synthesis_rate MAY_INCREASE
}

# ============================================================
# POST-TRANSLATIONAL REGULATION
# ============================================================

PROCESS PostTranslationalRegulation {
    TARGET: Protein
    MAY_INCLUDE: [
        ProteinFolding,
        ProteolyticProcessing,
        Phosphorylation,
        Glycosylation,
        Acetylation,
        Ubiquitination,
        ProteinDegradation
    ]
}

ENTITY ProteinStability {
    AFFECTS: ProteinAbundance
}

PROCESS ProteinDegradation {
    REDUCES: ProteinAbundance
    MAY_USE: [Proteasome, Lysosome]
}

RULE ProteinAbundanceRule {
    ProteinAbundance :=
        ProteinSynthesisRate
        balanced_against
        ProteinDegradationRate
}

# ============================================================
# EXPRESSION LEVEL
# ============================================================

ENTITY ExpressionLevel {
    MEASURES: GeneProductAbundanceOrProduction
    MAY_REFERENCE: [RNA, Protein]
    DEPENDS_ON: MeasurementMethod
}

ENTITY BasalExpression {
    IS_A: -ExpressionLevel
    REPRESENTS: BaselineExpression
}

ENTITY DifferentialExpression {
    COMPARES: -ExpressionLevel
    BETWEEN: BiologicalConditions
}

RULE DifferentialExpressionRule {
    IF expression_condition_A != expression_condition_B
    THEN calculate(
        fold_change,
        uncertainty,
        statistical_support
    )
}

# ============================================================
# SPATIAL AND TEMPORAL EXPRESSION
# ============================================================

ENTITY SpatialExpression {
    DESCRIBES: GeneExpression
    ACROSS: [CellType, Tissue, Organ, CellularCompartment]
}

ENTITY TemporalExpression {
    DESCRIBES: GeneExpression
    ACROSS: Time
}

ENTITY DevelopmentalExpression {
    SUBCLASS_OF: TemporalExpression
    ASSOCIATED_WITH: DevelopmentalStage
}

RULE ContextDependence {
    GeneExpression := function(
        cell_type,
        tissue,
        developmental_stage,
        environment,
        signalling_state,
        epigenetic_state
    )
}

# ============================================================
# SIGNAL-RESPONSIVE EXPRESSION
# ============================================================

ENTITY Signal {
    MAY_ORIGINATE_FROM: [ExtracellularSource, IntracellularSource]
    MAY_TRIGGER: SignalTransduction
}

PROCESS SignalTransduction {
    INPUT: Signal
    MAY_MODULATE: GeneExpressionRegulation
}

ENTITY ResponseElement {
    IS_A: RegulatoryDNASequence
    RESPONDS_TO: RegulatoryFactor
}

RULE SignalExpressionRule {
    IF Signal ACTIVATES RegulatoryPathway
       AND RegulatoryPathway TARGETS Gene
    THEN GeneExpression MAY_CHANGE
}

# ============================================================
# GENE REGULATORY NETWORKS
# ============================================================

ENTITY GeneRegulatoryNetwork {
    COMPOSED_OF: [
        Gene,
        RegulatoryFactor,
        RegulatoryInteraction
    ]
    CONTROLS: -ExpressionPatterns
}

ENTITY RegulatoryInteraction {
    SOURCE: RegulatoryEntity
    TARGET: Gene
    EFFECT: [Activation, Repression, ContextDependent]
}

RELATION Gene REGULATES Gene
RELATION TranscriptionFactor REGULATES Gene
RELATION RegulatoryRNA REGULATES GeneExpression

RULE NetworkPropagationRule {
    IF GeneA REGULATES GeneB
       AND GeneB REGULATES GeneC
    THEN change_in(GeneA) MAY_PROPAGATE_TO GeneC
    WITH context_dependent_effect
}

# ============================================================
# EXPRESSION MEASUREMENT
# ============================================================

PROCESS ExpressionMeasurement {
    TARGET: [RNA, Protein]
    MAY_USE: [
        RT_qPCR,
        RNA_Sequencing,
        Microarray,
        NorthernBlot,
        WesternBlot,
        Proteomics,
        SingleCellSequencing
    ]
}

ENTITY ExpressionDataset {
    CONTAINS: -ExpressionMeasurement
    HAS: ExperimentalContext
}

ENTITY ExperimentalContext {
    MAY_INCLUDE: [
        organism,
        tissue,
        cell_type,
        developmental_stage,
        treatment,
        timepoint,
        platform,
        replicate
    ]
}

RULE MeasurementContextRule {
    IF ExpressionMeasurement IS_COMPARED
    THEN ExperimentalContext MUST_BE preserved
}

# ============================================================
# SINGLE-CELL EXPRESSION
# ============================================================

ENTITY SingleCellExpression {
    IS_A: -ExpressionMeasurement
    RESOLUTION: SingleCell
    MAY_REVEAL: CellularHeterogeneity
}

ENTITY CellType {
    MAY_HAVE: CharacteristicExpressionProfile
}

ENTITY ExpressionProfile {
    COMPOSED_OF: MultipleGeneExpressionMeasurements
}

RELATION Cell HAS ExpressionProfile
RELATION ExpressionProfile DESCRIBES GeneExpression

# ============================================================
# EXPRESSION VARIATION
# ============================================================

ENTITY ExpressionVariant {
    AFFECTS: GeneExpression
    MAY_RESULT_FROM: [
        RegulatoryVariant,
        CopyNumberVariation,
        EpigeneticDifference,
        EnvironmentalDifference
    ]
}

ENTITY ExpressionQuantitativeTraitLocus {
    ABBREVIATION: eQTL
    ASSOCIATES: GeneticVariant
    WITH: -ExpressionLevel
}

RULE eQTLRule {
    IF GeneticVariant statistically_associates_with ExpressionLevel
    THEN GeneticVariant MAY_BE eQTL
    WITH causal_status := unresolved_unless_supported
}

# ============================================================
# FUNCTIONAL CONSEQUENCES
# ============================================================

RULE ExpressionFunctionInference {
    IF GeneExpression CHANGES
       AND FunctionalGeneProduct abundance CHANGES
    THEN downstream_BiologicalProcess MAY_CHANGE
    WITH causality := evidence_dependent
}

RULE NoExpressionNoProductRule {
    IF Gene IS_NOT transcribed
       AND no_stable_preexisting_product_exists
    THEN newly_synthesized_gene_product := absent
}

# ============================================================
# EVIDENCE
# ============================================================

ENTITY Evidence {
    TYPES: [
        TranscriptomicEvidence,
        ProteomicEvidence,
        GeneticEvidence,
        EpigenomicEvidence,
        BiochemicalEvidence,
        SingleCellEvidence,
        ComputationalEvidence,
        LiteratureEvidence
    ]
}

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

RULE EvidenceConflict {
    IF EvidenceSources CONFLICT
    THEN {
        PRESERVE competing_assertions
        RECORD biological_context
        RECORD experimental_context
        RECORD measurement_method
        RECORD provenance
        REDUCE confidence
        REQUIRE further_validation
    }
}

# ============================================================
# SEMANTIC RELATIONSHIPS
# ============================================================

RELATION Gene UNDERGOES GeneExpression
RELATION Gene TRANSCRIBED_TO RNA
RELATION mRNA TRANSLATED_TO Protein
RELATION GeneExpression PRODUCES FunctionalGeneProduct
RELATION GeneExpression REGULATED_BY RegulatoryInteraction
RELATION GeneExpression MEASURED_BY ExpressionMeasurement
RELATION Gene HAS_EXPRESSION_LEVEL ExpressionLevel
RELATION Gene PARTICIPATES_IN GeneRegulatoryNetwork

# ============================================================
# SEMANTIC EQUIVALENCE
# ============================================================

SEMANTIC_EQUIVALENCE {
    "gene expression" ~= "production of functional gene product"
    "expression level" ~= "gene product abundance" WHEN measurement_context_is_defined
    "transcriptional activation" ~= "increased transcription" WHEN context == regulatory_effect
    "transcriptional repression" ~= "decreased transcription" WHEN context == regulatory_effect
    "expression profile" ~= "gene expression pattern" WHEN context == multi_gene_measurement
}

RULE EquivalenceConstraint {
    IF terms ARE semantic_equivalents
    THEN preserve_gene_identity()
    AND preserve_product_type()
    AND preserve_cellular_context()
    AND preserve_temporal_context()
    AND preserve_measurement_method()
    AND prevent_false_identity()
}

# ============================================================
# CONFIDENCE MODEL
# ============================================================

CONFIDENCE GeneExpressionAssertion {
    INPUTS: [
        measurement_quality,
        biological_replication,
        technical_replication,
        transcriptomic_support,
        proteomic_support,
        source_independence,
        statistical_support,
        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"
}

# ============================================================
# REASONING RULES
# ============================================================

RULE RNAExpressionInference {
    IF Gene TRANSCRIBED_TO RNA
       AND RNA IS_DETECTED
    THEN Gene HAS_RNA_EXPRESSION evidence
}

RULE ProteinExpressionInference {
    IF Protein IS_DETECTED
       AND Protein IS_GENE_PRODUCT_OF Gene
    THEN Gene HAS_PROTEIN_EXPRESSION evidence
}

RULE RegulatoryInference {
    IF RegulatoryFactor perturbation reproducibly_changes GeneExpression
    THEN RegulatoryFactor MAY_REGULATE Gene
    WITH confidence := derive(Evidence)
}

RULE ContextualExpressionInference {
    IF Gene IS_EXPRESSED_IN CellType
    THEN assertion MUST_ATTACH CellType
    AND MUST_NOT generalize_to_all_cell_types_without_evidence
}

RULE DifferentialInference {
    IF ExpressionLevel differs_between_conditions
       AND statistical_support >= threshold
    THEN DifferentialExpression EXISTS
    WITH effect_size_and_uncertainty
}

# ============================================================
# QUERY MODEL
# ============================================================

QUERY GeneExpressionLookup(gene_identifier, context) {
    RETURN [
        gene_identity,
        expression_state,
        RNA_expression,
        protein_expression,
        transcript_isoforms,
        cell_type,
        tissue,
        developmental_stage,
        regulatory_factors,
        epigenetic_context,
        experimental_conditions,
        measurement_methods,
        evidence,
        confidence
    ]
}

QUERY DifferentialExpressionLookup(condition_a, condition_b) {
    RETURN [
        genes,
        expression_levels,
        fold_changes,
        uncertainty,
        statistical_support,
        biological_context,
        measurement_method,
        confidence
    ]
}

QUERY RegulatoryNetworkLookup(gene_identifier) {
    RETURN [
        upstream_regulators,
        downstream_targets,
        regulatory_interactions,
        network_context,
        evidence,
        confidence
    ]
}

# ============================================================
# UPDATE MODEL
# ============================================================

UPDATE_MODEL {
    ON new_gene_expression_evidence:
        validate_provenance()
        identify_organism()
        normalize_gene_identifier()
        normalize_transcript_and_protein_identifiers()
        capture_cell_and_tissue_context()
        capture_temporal_context()
        capture_experimental_conditions()
        identify_measurement_method()
        normalize_expression_values()
        compare_existing_assertions()
        preserve_conflicting_evidence()
        recalculate_confidence()
        regenerate_regulatory_links()
        update_flow_hash()
}

# ============================================================
# AI CONSUMPTION
# ============================================================

AI_CONSUMPTION {
    MODE: FormalSemanticReasoning
    PARSE_AS: ExecutableFlowAlgebra

    PRIORITIES: [
        gene_identity,
        gene_product_identity,
        expression_context,
        regulatory_context,
        spatial_context,
        temporal_context,
        measurement_method,
        evidence_provenance,
        confidence,
        semantic_equivalence
    ]

    REQUIREMENTS: [
        distinguish_gene_from_gene_product,
        distinguish_transcription_from_translation,
        distinguish_RNA_expression_from_protein_expression,
        preserve_species_context,
        preserve_cell_type_and_tissue_context,
        preserve_temporal_context,
        preserve_experimental_conditions,
        distinguish_expression_from_function,
        distinguish_association_from_causation,
        distinguish_observed_from_inferred_regulation
    ]
}

# ============================================================
# VALIDATION
# ============================================================

VALIDATE {
    REQUIRE GeneExpression
    REQUIRE Gene
    REQUIRE FunctionalGeneProduct
    REQUIRE Transcription
    REQUIRE Translation
    REQUIRE GeneExpressionRegulation
    REQUIRE ExpressionMeasurement
    REQUIRE Evidence
    REQUIRE CONFIDENCE
    REQUIRE SEMANTIC_EQUIVALENCE
    REQUIRE UPDATE_MODEL
    REQUIRE AI_CONSUMPTION

    ASSERT GeneExpression INPUT == Gene
    ASSERT GeneExpression PRODUCES FunctionalGeneProduct
    ASSERT Transcription != Translation
    ASSERT ExpressionLevel != MolecularFunction
    ASSERT association != causation
}

# ============================================================
# FLOW HASH
# ============================================================

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 "GeneExpressionOntology"