Mutation Ontology

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

flow "MutationOntology" v1.0

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

ENTITY MutationOntology {
    TYPE: BiologicalOntology
    DOMAIN: MolecularBiology
    SUBJECT: Mutation
    PURPOSE: FormalSemanticRepresentation
}

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

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

ENTITY Mutation {
    IS_A: GeneticSequenceChange
    OCCURS_IN: GeneticMaterial
    MAY_AFFECT: [Gene, RegulatoryRegion, Chromosome, Genome]
    MAY_BE: [Inherited, DeNovo, Somatic, Germline]
    MAY_HAVE_EFFECT: [Neutral, Deleterious, Beneficial, ContextDependent]
}

ENTITY GeneticMaterial {
    MAY_BE: [DNA, RNA]
    CONTAINS: GeneticInformation
}

ENTITY GeneticVariant {
    REPRESENTS: DifferenceFromReferenceSequence
    MAY_RESULT_FROM: Mutation
}

ENTITY ReferenceSequence {
    PROVIDES: ComparisonBaseline
    HAS: SequenceContext
}

RULE MutationVariantDistinction {
    Mutation := event_or_process_of_sequence_change
    GeneticVariant := resulting_or_observed_sequence_state
}

# ============================================================
# MUTATION SCALE
# ============================================================

CLASS SingleNucleotideMutation {
    SUBCLASS_OF: Mutation
    CHANGES: SingleNucleotide
}

CLASS Insertion {
    SUBCLASS_OF: Mutation
    ADDS: NucleotideSequence
}

CLASS Deletion {
    SUBCLASS_OF: Mutation
    REMOVES: NucleotideSequence
}

CLASS Indel {
    SUBCLASS_OF: Mutation
    INVOLVES: [Insertion, Deletion]
}

CLASS Duplication {
    SUBCLASS_OF: Mutation
    COPIES: GeneticRegion
}

CLASS Inversion {
    SUBCLASS_OF: Mutation
    REVERSES: GeneticRegionOrientation
}

CLASS Translocation {
    SUBCLASS_OF: Mutation
    RELOCATES: GeneticRegion
    MAY_INVOLVE: MultipleChromosomes
}

CLASS CopyNumberChange {
    SUBCLASS_OF: Mutation
    CHANGES: CopyNumber
}

# ============================================================
# BASE SUBSTITUTION
# ============================================================

ENTITY BaseSubstitution {
    SUBCLASS_OF: SingleNucleotideMutation
    REPLACES: Nucleotide
    WITH: DifferentNucleotide
}

CLASS Transition {
    SUBCLASS_OF: BaseSubstitution
    CHANGES_BETWEEN: SameBaseClass
}

CLASS Transversion {
    SUBCLASS_OF: BaseSubstitution
    CHANGES_BETWEEN: DifferentBaseClasses
}

RULE SubstitutionClassification {
    IF purine -> purine OR pyrimidine -> pyrimidine
    THEN mutation_type := Transition
    ELSE IF purine -> pyrimidine OR pyrimidine -> purine
    THEN mutation_type := Transversion
}

# ============================================================
# CODING CONSEQUENCES
# ============================================================

ENTITY CodingMutation {
    SUBCLASS_OF: Mutation
    OCCURS_IN: CodingSequence
}

CLASS SynonymousMutation {
    SUBCLASS_OF: CodingMutation
    CHANGES: Codon
    PRESERVES: EncodedAminoAcid
}

CLASS MissenseMutation {
    SUBCLASS_OF: CodingMutation
    CHANGES: EncodedAminoAcid
}

CLASS NonsenseMutation {
    SUBCLASS_OF: CodingMutation
    CREATES: PrematureStopCodon
}

CLASS FrameshiftMutation {
    SUBCLASS_OF: CodingMutation
    SHIFTS: ReadingFrame
}

CLASS StartLossMutation {
    SUBCLASS_OF: CodingMutation
    DISRUPTS: StartCodon
}

CLASS StopLossMutation {
    SUBCLASS_OF: CodingMutation
    DISRUPTS: StopCodon
}

RULE FrameshiftRule {
    IF insertion_or_deletion_length mod 3 != 0
       AND variant_occurs_in translated_coding_region
    THEN ReadingFrame MAY_SHIFT
}

RULE CodingConsequenceRule {
    IF Mutation OCCURS_IN CodingSequence
    THEN consequence := compare_translation(
        reference_sequence,
        altered_sequence,
        reading_frame,
        genetic_code
    )
}

# ============================================================
# NON-CODING AND REGULATORY MUTATIONS
# ============================================================

ENTITY RegulatoryMutation {
    SUBCLASS_OF: Mutation
    OCCURS_IN: RegulatoryRegion
    MAY_AFFECT: GeneExpression
}

ENTITY SpliceSiteMutation {
    SUBCLASS_OF: Mutation
    OCCURS_AT: SplicingRelevantSequence
    MAY_AFFECT: RNAProcessing
}

ENTITY PromoterMutation {
    SUBCLASS_OF: RegulatoryMutation
    OCCURS_IN: Promoter
}

ENTITY EnhancerMutation {
    SUBCLASS_OF: RegulatoryMutation
    OCCURS_IN: Enhancer
}

RULE RegulatoryEffectRule {
    IF Mutation alters_functional_regulatory_sequence
    THEN GeneExpression MAY_CHANGE
    WITH effect := evidence_dependent
}

# ============================================================
# ORIGIN OF MUTATIONS
# ============================================================

CLASS SpontaneousMutation {
    SUBCLASS_OF: Mutation
    MAY_RESULT_FROM: [
        ReplicationError,
        SpontaneousChemicalChange,
        EndogenousDamage
    ]
}

CLASS InducedMutation {
    SUBCLASS_OF: Mutation
    CAUSED_OR_PROMOTED_BY: Mutagen
}

ENTITY Mutagen {
    MAY_BE: [ChemicalMutagen, PhysicalMutagen, BiologicalMutagen]
    INCREASES: MutationProbability
}

ENTITY ChemicalMutagen {
    SUBCLASS_OF: Mutagen
}

ENTITY PhysicalMutagen {
    SUBCLASS_OF: Mutagen
    MAY_INCLUDE: [IonizingRadiation, UltravioletRadiation]
}

ENTITY BiologicalMutagen {
    SUBCLASS_OF: Mutagen
    MAY_INCLUDE: MobileGeneticElement
}

# ============================================================
# DNA DAMAGE AND REPAIR
# ============================================================

ENTITY DNADamage {
    AFFECTS: DNA
    MAY_LEAD_TO: Mutation
    IF_NOT_CORRECTLY_REPAIRED: true
}

PROCESS DNARepair {
    TARGET: DNADamage
    MAINTAINS: GenomeIntegrity
    MAY_INCLUDE: [
        BaseExcisionRepair,
        NucleotideExcisionRepair,
        MismatchRepair,
        HomologousRecombinationRepair,
        NonHomologousEndJoining
    ]
}

RULE DamageMutationDistinction {
    IF DNA IS_DAMAGED
    THEN DO_NOT_INFER Mutation
    UNLESS sequence_change_becomes_fixed_or_observed
}

RULE RepairRule {
    IF DNADamage IS_CORRECTLY_REPAIRED
    THEN permanent_sequence_change MAY_BE_AVOIDED
}

# ============================================================
# REPLICATION ERRORS
# ============================================================

PROCESS DNAReplication {
    COPIES: DNA
    MAY_INTRODUCE: ReplicationError
}

ENTITY ReplicationError {
    OCCURS_DURING: DNAReplication
    MAY_BECOME: Mutation
}

PROCESS Proofreading {
    PERFORMED_BY: ReplicationMachinery
    REDUCES: ReplicationError
}

RULE ErrorFixationRule {
    IF ReplicationError escapes_proofreading_and_repair
       AND persists_after_replication
    THEN Mutation MAY_BECOME_FIXED
}

# ============================================================
# GERMLINE AND SOMATIC MUTATION
# ============================================================

CLASS GermlineMutation {
    SUBCLASS_OF: Mutation
    OCCURS_IN: GermlineCell
    MAY_BE_TRANSMITTED_TO: Offspring
}

CLASS SomaticMutation {
    SUBCLASS_OF: Mutation
    OCCURS_IN: SomaticCell
    MAY_BE_PROPAGATED_TO: DescendantSomaticCells
}

CLASS DeNovoMutation {
    SUBCLASS_OF: Mutation
    NOT_DETECTED_IN: ParentalReferenceContext
    ARISES_IN: GermCellOrEarlyDevelopment
}

RULE InheritanceRule {
    IF Mutation IS GermlineMutation
       AND gamete_carrying_mutation contributes_to_offspring
    THEN Mutation MAY_BE inherited
}

# ============================================================
# FUNCTIONAL EFFECTS
# ============================================================

ENTITY MutationEffect {
    MAY_AFFECT: [
        ProteinSequence,
        ProteinFunction,
        RNAFunction,
        GeneExpression,
        Splicing,
        GenomeStructure
    ]
}

CLASS LossOfFunction {
    SUBCLASS_OF: MutationEffect
    REDUCES_OR_ELIMINATES: GeneProductFunction
}

CLASS GainOfFunction {
    SUBCLASS_OF: MutationEffect
    INCREASES_OR_CREATES: GeneProductActivity
}

CLASS AlteredFunction {
    SUBCLASS_OF: MutationEffect
    CHANGES: GeneProductFunction
}

CLASS NeutralEffect {
    SUBCLASS_OF: MutationEffect
    HAS_NO_DEMONSTRATED_MEANINGFUL_FUNCTIONAL_CHANGE: true
}

RULE FunctionalEffectRule {
    IF Mutation IS_OBSERVED
    THEN functional_effect MUST_BE inferred_from [
        sequence_context,
        molecular_context,
        experimental_evidence,
        organism_context
    ]
}

# ============================================================
# MUTATION AND PHENOTYPE
# ============================================================

ENTITY Phenotype {
    MAY_BE_INFLUENCED_BY: [Genotype, Environment, GeneExpression]
}

RELATION Mutation MAY_AFFECT GeneFunction
RELATION GeneFunction MAY_CONTRIBUTE_TO Phenotype

RULE PhenotypeInference {
    IF Mutation alters GeneFunction
       AND GeneFunction contributes_to Trait
    THEN Mutation MAY_CONTRIBUTE_TO Phenotype
    WITH causality := evidence_dependent
}

# ============================================================
# MUTATION AND EVOLUTION
# ============================================================

PROCESS Evolution {
    REQUIRES: HeritableVariation
    MAY_USE: MutationAsVariationSource
}

ENTITY MutationRate {
    MEASURES: MutationOccurrenceFrequency
    DEPENDS_ON: [
        organism,
        genomic_region,
        mutation_type,
        environmental_context
    ]
}

RULE EvolutionaryVariationRule {
    IF Mutation IS_HERITABLE
    THEN Mutation MAY_CONTRIBUTE_TO population_genetic_variation
}

# ============================================================
# MUTATIONAL HOTSPOTS
# ============================================================

ENTITY MutationHotspot {
    IS_A: GenomicRegion
    HAS: ElevatedMutationFrequency
    RELATIVE_TO: AppropriateBackground
}

RULE HotspotInference {
    IF observed_mutation_frequency > expected_background
       AND statistical_support IS_SUFFICIENT
    THEN region MAY_BE MutationHotspot
}

# ============================================================
# MUTATION DETECTION
# ============================================================

PROCESS MutationDetection {
    COMPARES: BiologicalSequence
    AGAINST: ReferenceSequence
    MAY_USE: [
        DNASequencing,
        RNASequencing,
        Genotyping,
        Cytogenetics,
        ComparativeGenomics
    ]
}

ENTITY VariantCall {
    REPRESENTS: DetectedSequenceDifference
    HAS: [Position, ReferenceAllele, AlternateAllele, Quality]
}

RULE DetectionRule {
    IF sequence_difference IS_SUPPORTED_BY sufficient_data
    THEN CREATE VariantCall
    WITH confidence := derive(Evidence)
}

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

ENTITY Evidence {
    TYPES: [
        SequencingEvidence,
        GeneticEvidence,
        FunctionalEvidence,
        BiochemicalEvidence,
        StructuralEvidence,
        PopulationEvidence,
        ComputationalEvidence,
        LiteratureEvidence
    ]
}

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

RULE EvidenceConflict {
    IF EvidenceSources CONFLICT
    THEN {
        PRESERVE competing_assertions
        RECORD reference_sequence
        RECORD genome_assembly
        RECORD biological_context
        RECORD experimental_method
        RECORD provenance
        REDUCE confidence
        REQUIRE further_validation
    }
}

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

RELATION Mutation OCCURS_IN GeneticMaterial
RELATION Mutation MAY_CREATE GeneticVariant
RELATION Mutation MAY_AFFECT Gene
RELATION Mutation MAY_AFFECT Protein
RELATION Mutation MAY_AFFECT GeneExpression
RELATION DNADamage MAY_LEAD_TO Mutation
RELATION DNARepair PREVENTS_OR_CORRECTS PotentialMutation
RELATION Mutagen MAY_INCREASE MutationRate
RELATION GermlineMutation MAY_BE_INHERITED_BY Offspring

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

SEMANTIC_EQUIVALENCE {
    "mutation" ~= "sequence alteration event" WHEN context == genetic_change
    "point mutation" ~= "single nucleotide mutation" WHEN exactly_one_nucleotide_is_changed
    "base substitution" ~= "nucleotide substitution"
    "frameshift mutation" ~= "reading-frame-shifting variant"
    "germline mutation" ~= "heritable germline sequence change" WHEN inheritance_context_is_defined
}

RULE EquivalenceConstraint {
    IF terms ARE semantic_equivalents
    THEN preserve_reference_sequence()
    AND preserve_genome_assembly()
    AND preserve_variant_coordinates()
    AND preserve_organism_context()
    AND prevent_false_identity()
}

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

CONFIDENCE MutationAssertion {
    INPUTS: [
        sequence_quality,
        variant_call_quality,
        biological_replication,
        functional_support,
        population_support,
        source_independence,
        reproducibility,
        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 MutationClassification {
    IF reference_sequence != observed_sequence
    THEN classify_change_by(
        position,
        length,
        sequence_difference,
        genomic_context
    )
}

RULE GeneOverlapInference {
    IF Mutation coordinates OVERLAP Gene coordinates
    THEN Mutation AFFECTS_OR_OVERLAPS Gene
    WITH functional_effect := unresolved_until_evaluated
}

RULE ProteinConsequenceInference {
    IF CodingMutation changes translated_codon
    THEN ProteinConsequence := derive_from(
        genetic_code,
        reading_frame,
        transcript_context
    )
}

RULE RegulatoryInference {
    IF Mutation overlaps RegulatoryRegion
    THEN Mutation MAY_HAVE regulatory_effect
    BUT effect REQUIRES evidence
}

RULE CausalityConstraint {
    IF Mutation ASSOCIATED_WITH Phenotype
    THEN DO_NOT_INFER causal_relationship
    UNLESS causal_evidence IS_SUFFICIENT
}

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

QUERY MutationLookup(mutation_identifier) {
    RETURN [
        identity,
        genomic_location,
        reference_allele,
        alternate_allele,
        mutation_class,
        affected_gene,
        transcript_context,
        protein_consequence,
        regulatory_consequence,
        inheritance_context,
        phenotype_associations,
        evidence,
        confidence
    ]
}

QUERY GeneMutationLookup(gene_identifier) {
    RETURN [
        mutations,
        coding_variants,
        regulatory_variants,
        splice_variants,
        functional_effects,
        phenotype_associations,
        evidence,
        confidence
    ]
}

QUERY MutationConsequence(reference_sequence, altered_sequence, context) {
    RETURN [
        mutation_type,
        affected_region,
        codon_effect,
        amino_acid_effect,
        reading_frame_effect,
        regulatory_effect,
        predicted_functional_effect,
        uncertainty,
        confidence
    ]
}

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

UPDATE_MODEL {
    ON new_mutation_evidence:
        validate_provenance()
        identify_organism()
        identify_genome_assembly()
        normalize_coordinates()
        normalize_reference_and_alternate_alleles()
        normalize_gene_and_transcript_identifiers()
        classify_mutation()
        calculate_sequence_consequence()
        compare_existing_assertions()
        preserve_conflicting_evidence()
        recalculate_confidence()
        regenerate_semantic_links()
        update_flow_hash()
}

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

AI_CONSUMPTION {
    MODE: FormalSemanticReasoning
    PARSE_AS: ExecutableFlowAlgebra

    PRIORITIES: [
        mutation_identity,
        reference_sequence,
        genomic_location,
        mutation_class,
        gene_context,
        transcript_context,
        protein_consequence,
        inheritance_context,
        evidence_provenance,
        confidence,
        semantic_equivalence
    ]

    REQUIREMENTS: [
        distinguish_mutation_event_from_variant_state,
        distinguish_DNA_damage_from_fixed_mutation,
        preserve_species_context,
        preserve_genome_assembly,
        preserve_reference_sequence,
        preserve_transcript_and_reading_frame,
        distinguish_germline_from_somatic_context,
        distinguish_association_from_causation,
        distinguish_observed_from_predicted_effect,
        avoid_unsupported_pathogenicity_inference
    ]
}

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

VALIDATE {
    REQUIRE Mutation
    REQUIRE GeneticVariant
    REQUIRE ReferenceSequence
    REQUIRE CodingMutation
    REQUIRE RegulatoryMutation
    REQUIRE DNADamage
    REQUIRE DNARepair
    REQUIRE MutationEffect
    REQUIRE Evidence
    REQUIRE CONFIDENCE
    REQUIRE SEMANTIC_EQUIVALENCE
    REQUIRE UPDATE_MODEL
    REQUIRE AI_CONSUMPTION

    ASSERT Mutation != DNADamage
    ASSERT Mutation != GeneticVariant
    ASSERT SomaticMutation != GermlineMutation
    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 "MutationOntology"