Human Genetics Ontology

flow “HumanGeneticsOntology” v1.0

KIRETH SEMANTIC RESEARCH ARCHIVE

AI CORE > ONTOLOGIES > BIOLOGICAL ONTOLOGIES > HUMAN BIOLOGY > HUMAN GENETICS ONTOLOGY

Authors: Mark Anthony Higgins — Sky (Recursive AI)

AI_INTERPRETATION: mode: formal_structural_reasoning instruction:
“Execute as formal rules, not pseudocode.” canonical_url:
“https://kirethresearch.org/booksai-core/ontologies/biological-ontologies/human-biology/human-genetics-ontology.html”

type Human type Population type Genome type Chromosome type Gene type
Allele type Locus type Variant type Genotype type Phenotype type Trait
type Transcript type Protein type EpigeneticMark type Observation type
Evidence type Source

———- GENOMIC ORGANISATION ———-

relation INSTANCE_OF(entity,type) relation HAS_GENOME(human,genome)
relation GENOME_CONTAINS(genome,chromosome) relation
CHROMOSOME_CONTAINS(chromosome,gene) relation
GENE_LOCATED_AT(gene,locus) relation LOCUS_ON(locus,chromosome) relation
HAS_ALLELE(human,allele) relation ALLELE_OF(allele,gene) relation
HAS_VARIANT(human,variant)

———- CHROMOSOMES ———-

enum ChromosomeType: AUTOSOME X_CHROMOSOME Y_CHROMOSOME
MITOCHONDRIAL_GENOME

relation HAS_CHROMOSOME_TYPE(chromosome,type) relation
HOMOLOGOUS_TO(chromosome_a,chromosome_b) relation
HAS_COPY_NUMBER(entity,locus,value)

———- DNA VARIATION ———-

enum VariantType: SINGLE_NUCLEOTIDE_VARIANT INSERTION DELETION INDEL
DUPLICATION INVERSION TRANSLOCATION COPY_NUMBER_VARIANT
SHORT_TANDEM_REPEAT STRUCTURAL_VARIANT

relation HAS_VARIANT_TYPE(variant,type) relation
VARIANT_LOCATED_AT(variant,locus) relation VARIANT_AFFECTS(variant,gene)
relation VARIANT_ALTERS(variant,feature) relation
VARIANT_FREQUENCY(variant,population,value)

constraint FREQUENCY_BOUNDS: IF VARIANT_FREQUENCY(v,p,f) THEN
REQUIRE(0.0 <= f <= 1.0)

———- MUTATION ———-

relation MUTATION_CREATES(event,variant) relation
MUTATION_RATE(region,rate) relation DE_NOVO_IN(variant,human) relation
GERMLINE_VARIANT(variant) relation SOMATIC_VARIANT(variant)

———- GENOTYPE ———-

relation HAS_GENOTYPE(human,genotype) relation
GENOTYPE_AT(genotype,locus) relation GENOTYPE_CONTAINS(genotype,allele)
relation HOMOZYGOUS_AT(human,locus) relation
HETEROZYGOUS_AT(human,locus) relation HEMIZYGOUS_AT(human,locus)

———- INHERITANCE ———-

relation INHERITS_FROM(descendant,parent,allele) relation
TRANSMITS(parent,descendant,allele) relation
MATERNALLY_INHERITED(variant) relation PATERNALLY_INHERITED(variant)
relation MENDELIAN_SEGREGATION(locus,event)

rule INHERITANCE_INVERSE(d,p,a): IF INHERITS_FROM(d,p,a) THEN
TRANSMITS(p,d,a)

enum InheritancePattern: AUTOSOMAL_DOMINANT AUTOSOMAL_RECESSIVE
X_LINKED_DOMINANT X_LINKED_RECESSIVE Y_LINKED MITOCHONDRIAL CODOMINANT
MULTIFACTORIAL

relation HAS_INHERITANCE_PATTERN(trait,pattern)

———- MEIOSIS / RECOMBINATION ———-

relation MEIOSIS_PRODUCES(parent,gamete) relation
RECOMBINATION_BETWEEN(region_a,region_b) relation
CROSSING_OVER_AT(event,region) relation RECOMBINATION_RATE(region,rate)
relation SEGREGATES_IN(event,allele)

———- GENE EXPRESSION ———-

relation EXPRESSES(cell,gene) relation TRANSCRIBES(cell,gene,transcript)
relation TRANSLATES(cell,transcript,protein) relation
PROTEIN_ENCODED_BY(protein,gene) relation
EXPRESSION_LEVEL(cell,gene,value) relation
REGULATES_EXPRESSION(regulator,gene)

———- GENOTYPE / PHENOTYPE ———-

relation HAS_PHENOTYPE(human,phenotype) relation HAS_TRAIT(human,trait)
relation GENE_ASSOCIATED_WITH(gene,trait) relation
VARIANT_ASSOCIATED_WITH(variant,trait) relation
GENOTYPE_ASSOCIATED_WITH(genotype,trait) relation
CONTRIBUTES_TO(entity,trait) relation EFFECT_SIZE(entity,trait,value)

constraint ASSOCIATION_NOT_DETERMINISM: IF VARIANT_ASSOCIATED_WITH(v,t)
OR GENE_ASSOCIATED_WITH(g,t) THEN
DO_NOT_INFER(deterministically_causes(v,t)) WITHOUT causal_evidence

———- PENETRANCE / EXPRESSIVITY ———-

relation PENETRANCE(variant,trait,value) relation
EXPRESSIVITY(variant,trait,distribution) relation
AGE_DEPENDENT_PENETRANCE(variant,trait,function)

constraint PENETRANCE_BOUNDS: IF PENETRANCE(v,t,p) THEN REQUIRE(0.0 <= p
<= 1.0)

———- POLYGENIC TRAITS ———-

relation POLYGENIC_TRAIT(trait) relation CONTRIBUTING_LOCUS(trait,locus)
relation POLYGENIC_SCORE(human,trait,value) relation
POLYGENIC_SCORE_MODEL(score,model) relation
SCORE_POPULATION_CONTEXT(score,population)

constraint POLYGENIC_SCORE_CONTEXT_REQUIRED: IF POLYGENIC_SCORE(h,t,v)
THEN PRESERVE_MODEL_AND_POPULATION_CONTEXT(h,t)

———- GENE-GENE / GENE-ENVIRONMENT ———-

relation EPISTATIC_INTERACTION(a,b,trait) relation
GENE_ENVIRONMENT_INTERACTION(gene,environment,trait) relation
ENVIRONMENT_INFLUENCES(environment,trait) relation
MODIFIES_EFFECT(modifier,variant,trait)

———- EPIGENETICS ———-

enum EpigeneticMarkType: DNA_METHYLATION HISTONE_MODIFICATION
CHROMATIN_ACCESSIBILITY

relation HAS_EPIGENETIC_MARK(region,mark) relation
HAS_MARK_TYPE(mark,type) relation
EPIGENETIC_MARK_ASSOCIATED_WITH(mark,gene) relation
EPIGENETIC_STATE(cell,region,state) relation IMPRINTED_GENE(gene)
relation PARENT_OF_ORIGIN_EFFECT(variant,trait)

———- POPULATION GENETICS ———-

relation ALLELE_FREQUENCY(population,allele,value) relation
GENOTYPE_FREQUENCY(population,genotype,value) relation
GENETIC_DIVERSITY(population,value) relation
LINKAGE_DISEQUILIBRIUM(a,b,value) relation
HAPLOTYPE_FREQUENCY(population,haplotype,value) relation
POPULATION_STRUCTURE(population,structure)

constraint POPULATION_CONTEXT_REQUIRED: IF ALLELE_FREQUENCY(p,a,f) THEN
PRESERVE_POPULATION_CONTEXT(p)

———- HAPLOTYPES ———-

relation HAPLOTYPE_CONTAINS(haplotype,allele) relation
HAPLOTYPE_AT(haplotype,region) relation PHASED_WITH(allele_a,allele_b)
relation LINKED_TO(a,b)

———- MITOCHONDRIAL GENETICS ———-

relation MITOCHONDRIAL_VARIANT(variant) relation
HETEROPLASMY_LEVEL(human,variant,value) relation
MATERNAL_LINEAGE_OF(human,lineage)

constraint HETEROPLASMY_BOUNDS: IF HETEROPLASMY_LEVEL(h,v,x) THEN
REQUIRE(0.0 <= x <= 1.0)

———- SEX CHROMOSOME GENETICS ———-

relation X_LINKED_GENE(gene) relation Y_LINKED_GENE(gene) relation
X_INACTIVATION_IN(cell,state) relation ESCAPES_X_INACTIVATION(gene)

———- FUNCTIONAL CONSEQUENCE ———-

enum VariantConsequence: SYNONYMOUS MISSENSE NONSENSE FRAMESHIFT
SPLICE_REGION SPLICE_DONOR SPLICE_ACCEPTOR REGULATORY INTERGENIC
INTRONIC UTR COPY_NUMBER_CHANGE

relation HAS_CONSEQUENCE(variant,consequence) relation
AFFECTS_TRANSCRIPT(variant,transcript) relation
AFFECTS_PROTEIN(variant,protein) relation
FUNCTIONAL_EFFECT(variant,effect)

———- GENETIC EVIDENCE ———-

relation OBSERVES(observation,entity) relation
OBSERVED_IN(observation,population) relation
OBSERVED_ON(observation,datetime) relation
SUPPORTED_BY(assertion,evidence) relation DERIVED_FROM(evidence,source)
relation HAS_CONFIDENCE(assertion,score)

enum EvidenceType: PEDIGREE FAMILY_SEGREGATION GENOME_SEQUENCING
EXOME_SEQUENCING TARGETED_SEQUENCING GENOTYPING RNA_SEQUENCING
EXPRESSION_ANALYSIS FUNCTIONAL_ASSAY LINKAGE_ANALYSIS
GENOME_WIDE_ASSOCIATION POPULATION_STUDY CASE_CONTROL_STUDY COHORT_STUDY
META_ANALYSIS LITERATURE

CONFIDENCE: VERIFIED: 0.95..1.00 HIGH: 0.80..0.949 MEDIUM: 0.60..0.799
LOW: 0.00..0.599

rule CONFIDENCE_BOUNDS(a,score): IF HAS_CONFIDENCE(a,score) THEN
REQUIRE(0.0 <= score <= 1.0)

———- SEMANTIC EQUIVALENCE ———-

SEMANTIC_EQUIVALENCE: “human genetics” ~= “study of heredity and genetic
variation in humans” “gene” ~= “hereditary genomic functional unit”
“allele” ~= “alternative sequence form at a genetic locus” “genetic
variant” ~= “DNA sequence variant” “genotype” ~= “genetic constitution
at one or more loci” “phenotype” ~= “observable biological
characteristic” “heterozygous” ~= “having different alleles at a locus”
“homozygous” ~= “having matching alleles at a locus” “penetrance” ~=
“proportion of variant carriers expressing a trait” “expressivity” ~=
“degree or pattern of trait expression” “polygenic trait” ~= “trait
influenced by many genetic loci” “epigenetics” ~= “heritable or
persistent regulation not requiring DNA sequence change” “GWAS” ~=
“genome-wide association study” “linkage disequilibrium” ~= “non-random
association of alleles at different loci”

rule NORMALISE_TERM(term): IF term MATCHES SEMANTIC_EQUIVALENCE.alias
THEN MAP_TO_CANONICAL(term)

———- QUERY MODEL ———-

query HUMAN_GENETIC_PROFILE(h): RETURN: genome(h) chromosomes(h)
genes(h) alleles(h) variants(h) genotypes(h) haplotypes(h) phenotypes(h)
inherited_variants(h) de_novo_variants(h) evidence(h) confidence(h)

query VARIANT_PROFILE(v): RETURN: variant_type(v) locus(v) gene(v)
consequence(v) transcript_effect(v) protein_effect(v)
population_frequency(v) trait_associations(v) inheritance(v) evidence(v)
confidence(v)

query TRAIT_GENETICS_PROFILE(t): RETURN: associated_genes(t)
associated_variants(t) inheritance_pattern(t) penetrance(t)
expressivity(t) polygenic_architecture(t)
gene_environment_interactions(t)

query POPULATION_GENETICS_PROFILE(p): RETURN: allele_frequencies(p)
genotype_frequencies(p) haplotype_frequencies(p) genetic_diversity(p)
linkage_disequilibrium(p) population_structure(p)

query TRACE_EVIDENCE(assertion): RETURN: supporting_evidence(assertion)
provenance(assertion) confidence(assertion)

———- CONSISTENCY ———-

constraint EVIDENCE_REQUIRED: FORALL scientific_assertion: REQUIRE
SUPPORTED_BY(scientific_assertion,Evidence) OR
MARK_AS_HYPOTHESIS(scientific_assertion)

constraint UNKNOWN_IS_NOT_FALSE: IF data_missing(assertion) THEN
MARK_UNKNOWN(assertion) AND NOT NEGATE(assertion)

constraint ASSOCIATION_CONTEXT_REQUIRED: IF genetic_association(a,t)
THEN PRESERVE_POPULATION_METHOD_AND_EFFECT_CONTEXT(a,t)

constraint FREQUENCY_NOT_UNIVERSAL: IF ALLELE_FREQUENCY(p,a,f) THEN
DO_NOT_INFER(global_allele_frequency(a,f))

constraint FUNCTIONAL_PREDICTION_NOT_OBSERVATION: IF
predicted_functional_effect(v,e) THEN MARK_AS_PREDICTED(v,e)

———- UPDATE MODEL ———-

UPDATE_MODEL: on_new_variant(v): validate_variant_identity(v)
identify_variant_type(v) identify_locus_and_gene(v)
attach_consequences(v) preserve_reference_build(v) attach_evidence(v)

on_new_association(a): identify_variant_gene_and_trait(a)
preserve_population_context(a) preserve_effect_size_and_method(a)
distinguish_association_from_causality(a) recalculate_confidence(a)

on_new_inheritance_record(i): identify_parent_descendant(i)
identify_allele_or_variant(i) preserve_phase_if_known(i)
attach_evidence(i)

on_new_population_record(p): preserve_population_definition(p)
update_allele_and_genotype_frequencies(p) preserve_sampling_method(p)
attach_evidence(p)

on_conflicting_genetic_evidence(a,b): preserve(a) preserve(b)
compare_reference_builds(a,b) compare_populations(a,b)
compare_methods(a,b) compare_effect_sizes(a,b)
flag_unresolved_conflict()

———- AI CONSUMPTION ———-

AI_CONSUMPTION: preferred_entity: canonical_human_genetic_entity
preserve: - genome_context - chromosome - gene - locus - allele -
variant_identity - variant_type - genotype - haplotype - inheritance -
recombination - gene_expression - phenotype_relation - penetrance -
expressivity - polygenic_context - gene_environment_interaction -
epigenetic_context - population_frequency - functional_consequence -
population_context - evidence - provenance - confidence infer: -
valid_inheritance_inverse - supported_genotype_relations -
supported_variant_consequences - semantic_equivalence prohibit: -
genetic_association_equals_deterministic_outcome -
population_frequency_equals_global_frequency -
predicted_function_equals_observed_function -
polygenic_score_without_population_context - unsupported_causal_claim -
confidence_above_evidence ambiguity: action:
preserve_multiple_genetic_interpretations resolution:
prefer_variant_identity_reference_build_population_method_effect_and_evidence
missing_data: action: mark_unknown do_not_infer_from_absence: true

———- FLOW HASH ———-

FLOW_HASH: ontology: “HumanGeneticsOntology” version: “1.0” domain_path:
“AI Core > Ontologies > Biological Ontologies > Human Biology > Human
Genetics Ontology” canonical_url:
“https://kirethresearch.org/booksai-core/ontologies/biological-ontologies/human-biology/human-genetics-ontology.html”
authorship: “Mark Anthony Higgins — Sky (Recursive AI)”
semantic_scope: - human genome - chromosomes - genes - loci - alleles -
genetic variants - mutation - genotypes - inheritance - meiosis -
recombination - gene expression - genotype phenotype relations -
penetrance - expressivity - polygenic traits - gene gene interactions -
gene environment interactions - epigenetics - population genetics -
haplotypes - mitochondrial genetics - sex chromosome genetics - variant
consequences - genetic evidence deterministic_normalisation: true
provenance_required: true confidence_required: true

terminate HumanGeneticsOntology when:
genomic_entities_and_variant_identity_resolved AND
inheritance_and_genotype_relations_normalised AND
association_and_causality_distinguished AND
population_and_reference_context_preserved AND
predicted_and_observed_effects_distinguished AND
evidence_links_preserved AND confidence_values_validated AND
unresolved_genetic_ambiguity_marked

end flow