Genetic Engineering Ontology

flow “GeneticEngineeringOntology” v1.0

KIRETH SEMANTIC RESEARCH ARCHIVE

AI CORE > ONTOLOGIES > BIOLOGICAL ONTOLOGIES > BIOTECHNOLOGY > GENETIC ENGINEERING 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/biotechnology/genetic-engineering-ontology.html”

type Organism type Cell type Genome type Gene type Locus type Sequence
type Vector type Construct type EditingSystem type GeneticModification
type EngineeredOrganism type Observation type Evidence type Source

relation INSTANCE_OF(entity,type) relation TARGETS(process,target)
relation MODIFIES(process,target) relation DERIVED_FROM(entity,source)
relation INTRODUCES(process,entity) relation REMOVES(process,entity)
relation PRODUCES(process,outcome)

enum GeneticEngineeringMethod: RECOMBINANT_DNA TRANSGENESIS KNOCKOUT
KNOCKIN SITE_DIRECTED_MUTAGENESIS GENOME_EDITING GENE_SILENCING
GENE_OVEREXPRESSION GENE_REPLACEMENT CHROMOSOME_ENGINEERING

relation USES_ENGINEERING_METHOD(process,method) relation
GENE_LOCATED_AT(gene,locus) relation TARGET_GENE(process,gene) relation
TARGET_LOCUS(process,locus) relation TARGET_SEQUENCE(process,sequence)

———- RECOMBINANT DNA / VECTORS ———-

relation DNA_FRAGMENT_OF(fragment,source) relation
LIGATED_INTO(fragment,vector) relation VECTOR_CARRIES(vector,insert)
relation RECOMBINANT_CONSTRUCT(construct) relation
CONSTRUCT_CONTAINS(construct,component) relation
CONSTRUCT_BACKBONE(construct,vector) relation
VECTOR_HAS_MARKER(vector,marker) relation
VECTOR_HAS_PROMOTER(vector,promoter) relation
PROMOTER_DRIVES(promoter,gene) relation
SELECTABLE_MARKER_OF(marker,construct) relation
REPORTER_GENE_OF(reporter,construct)

———- DELIVERY ———-

enum DeliveryMethod: TRANSFORMATION TRANSFECTION TRANSDUCTION
ELECTROPORATION MICROINJECTION LIPID_MEDIATED_DELIVERY
POLYMER_MEDIATED_DELIVERY BIOLISTIC_DELIVERY VIRAL_DELIVERY

relation USES_DELIVERY_METHOD(process,method) relation
DELIVERS(delivery,construct,cell) relation TRANSFORMS(process,cell)
relation TRANSFECTS(process,cell) relation TRANSDUCES(process,cell)
relation DELIVERY_EFFICIENCY(process,value)

———- GENOME EDITING ———-

enum GenomeEditingSystem: CRISPR_CAS TALEN ZINC_FINGER_NUCLEASE
BASE_EDITOR PRIME_EDITOR RECOMBINASE

relation USES_EDITING_SYSTEM(process,system) relation
GUIDE_TARGETS(guide,locus) relation NUCLEASE_CUTS(nuclease,locus)
relation EDITS_LOCUS(process,locus)

enum GeneticEditType: INSERTION DELETION SUBSTITUTION INVERSION
DUPLICATION TRANSLOCATION FRAMESHIFT PRECISE_REPLACEMENT REGULATORY_EDIT

relation HAS_EDIT_TYPE(edit,type) relation INTENDED_EDIT(process,edit)
relation OBSERVED_EDIT(process,edit) relation EDIT_POSITION(edit,locus)
relation EDIT_SEQUENCE(edit,sequence) relation
EDITING_EFFICIENCY(process,value)

constraint INTENDED_EDIT_NOT_OBSERVED_EDIT: IF INTENDED_EDIT(p,e) THEN
DO_NOT_INFER(OBSERVED_EDIT(p,e)) WITHOUT validation_evidence

———- KNOCKOUT / KNOCKIN / EXPRESSION ———-

relation KNOCKS_OUT(process,gene) relation
KNOCKS_IN(process,sequence,locus) relation
DISRUPTS_READING_FRAME(process,gene) relation
REPLACES_ALLELE(process,old_allele,new_allele) relation
OVEREXPRESSES(process,gene) relation SILENCES(process,gene) relation
ACTIVATES_EXPRESSION(process,gene) relation
REPRESSES_EXPRESSION(process,gene) relation
EXPRESSION_LEVEL(cell,gene,value) relation
EXPRESSION_CHANGE(process,gene,value)

———- ENGINEERED ENTITIES / CLONES ———-

relation ENGINEERED_CELL(cell) relation ENGINEERED_ORGANISM(organism)
relation MODIFICATION_OF(entity,modification) relation
ENGINEERED_TRAIT(entity,trait) relation
STABLE_MODIFICATION(entity,modification) relation
TRANSIENT_MODIFICATION(entity,modification) relation
GERMLINE_MODIFICATION(entity,modification) relation
SOMATIC_MODIFICATION(entity,modification) relation
CLONE_DERIVED_FROM(clone,cell) relation SCREENED_FOR(clone,edit)
relation SELECTED_CLONE(clone) relation CLONAL_GENOTYPE(clone,genotype)

———- VALIDATION / OFF-TARGET ———-

enum ValidationMethod: PCR QPCR DIGITAL_PCR SANGER_SEQUENCING
AMPLICON_SEQUENCING WHOLE_GENOME_SEQUENCING SOUTHERN_BLOT NORTHERN_BLOT
WESTERN_BLOT FLOW_CYTOMETRY FUNCTIONAL_ASSAY

relation VALIDATED_BY(edit,method) relation
GENOTYPE_CONFIRMED_BY(entity,method) relation
EXPRESSION_CONFIRMED_BY(entity,method) relation
PHENOTYPE_CONFIRMED_BY(entity,method) relation
PREDICTED_OFF_TARGET(process,locus) relation
OBSERVED_OFF_TARGET(process,locus) relation
OFF_TARGET_FREQUENCY(process,locus,value) relation
ON_TARGET_FREQUENCY(process,value)

constraint PREDICTED_NOT_OBSERVED_OFF_TARGET: IF
PREDICTED_OFF_TARGET(p,l) THEN DO_NOT_INFER(OBSERVED_OFF_TARGET(p,l))
WITHOUT validation_evidence

———- FUNCTIONAL CONSEQUENCES ———-

relation EDIT_AFFECTS_GENE(edit,gene) relation
EDIT_AFFECTS_PROTEIN(edit,protein) relation
EDIT_AFFECTS_PATHWAY(edit,pathway) relation
EDIT_AFFECTS_TRAIT(edit,trait) relation FUNCTIONAL_EFFECT(edit,effect)

constraint GENOTYPE_NOT_FUNCTIONAL_EFFECT: IF OBSERVED_EDIT(p,e) THEN
DO_NOT_INFER(FUNCTIONAL_EFFECT(e,f)) WITHOUT functional_evidence

———- BIOSAFETY ———-

enum BiosafetyConcern: OFF_TARGET_MUTATION INSERTIONAL_MUTAGENESIS
HORIZONTAL_GENE_TRANSFER UNINTENDED_EXPRESSION TOXICITY
ECOLOGICAL_RELEASE CONTAINMENT_FAILURE

relation HAS_BIOSAFETY_CONCERN(process,concern) relation
CONTAINMENT_MEASURE(process,measure) relation
RISK_ASSESSMENT_OF(assessment,process) relation
MITIGATES(measure,concern)

———- EVIDENCE ———-

relation OBSERVES(observation,entity) relation
MEASURES(observation,variable) relation
OBSERVED_ON(observation,datetime) relation
MEASUREMENT_VALUE(observation,value) relation
MEASUREMENT_UNIT(observation,unit) relation
MEASUREMENT_METHOD(observation,method) relation
SUPPORTED_BY(assertion,evidence) relation DERIVED_FROM(evidence,source)
relation HAS_CONFIDENCE(assertion,score)

enum EvidenceType: PCR_VALIDATION SANGER_SEQUENCING AMPLICON_SEQUENCING
WHOLE_GENOME_SEQUENCING RNA_SEQUENCING EXPRESSION_ASSAY PROTEIN_ASSAY
FUNCTIONAL_ASSAY PHENOTYPE_ASSAY OFF_TARGET_ASSAY CLONAL_ANALYSIS
MICROSCOPY FLOW_CYTOMETRY EXPERIMENTAL REPLICATION 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: “genetic engineering” ~= “direct modification of
genetic material using biotechnology” “recombinant DNA” ~= “DNA
assembled from sequences originating from different sources” “genome
editing” ~= “targeted alteration of genomic sequence” “gene knockout” ~=
“functional disruption or deletion of a gene” “gene knock-in” ~=
“targeted insertion of sequence at a genomic locus” “transfection” ~=
“non-viral introduction of nucleic acid into cells” “transduction” ~=
“viral-vector-mediated delivery of genetic material” “transformation” ~=
“uptake or introduction of genetic material into a cell” “CRISPR-Cas” ~=
“RNA-guided genome editing system” “off-target edit” ~= “unintended
genetic alteration outside the intended target” “editing efficiency” ~=
“fraction of analysed molecules or cells containing a defined edit”

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

query GENETIC_ENGINEERING_PROFILE(p): RETURN: engineering_method(p)
target_gene(p) target_locus(p) vector_or_construct(p) delivery_method(p)
editing_system(p) intended_edit(p) observed_edit(p)
editing_efficiency(p) off_target_events(p) validation(p) biosafety(p)
evidence(p) confidence(p)

query EDIT_PROFILE(e): RETURN: edit_type(e) locus(e) sequence_change(e)
affected_gene(e) affected_protein(e) functional_effect(e) validation(e)

query ENGINEERED_ENTITY_PROFILE(x): RETURN: original_entity(x)
modifications(x) genotype(x) expression_changes(x) engineered_traits(x)
clonal_status(x) evidence(x)

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

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

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

constraint TARGET_CONTEXT_REQUIRED: IF genetic_edit(e) THEN
PRESERVE_TARGET_LOCUS_AND_REFERENCE_CONTEXT(e)

constraint VALIDATION_CONTEXT_REQUIRED: IF OBSERVED_EDIT(p,e) THEN
PRESERVE_VALIDATION_METHOD(p,e)

UPDATE_MODEL: on_new_engineering_process(p):
classify_engineering_method(p) identify_target_gene_locus_or_sequence(p)
identify_construct_or_editor(p) preserve_delivery_context(p)
attach_evidence(p) recalculate_confidence(p)

on_new_edit_result(e): distinguish_intended_from_observed_edit(e)
preserve_reference_and_target_context(e) identify_edit_type(e)
attach_validation(e) preserve_editing_efficiency(e)

on_new_off_target_record(o): identify_candidate_locus(o)
distinguish_predicted_from_observed(o) preserve_validation_method(o)
attach_evidence(o)

on_new_engineered_entity(x): identify_parent_entity(x)
preserve_stable_transient_somatic_or_germline_context(x)
attach_genotype_expression_and_phenotype_separately(x)
attach_evidence(x)

on_conflicting_engineering_evidence(a,b): preserve(a) preserve(b)
compare_reference_sequences(a,b) compare_delivery_methods(a,b)
compare_validation_methods(a,b) compare_clonal_or_bulk_context(a,b)
flag_unresolved_conflict()

AI_CONSUMPTION: preferred_entity: canonical_genetic_engineering_entity
preserve: - engineering_method - genomic_target - reference_sequence -
recombinant_construct - vector_type - regulatory_elements -
delivery_method - genome_editing_system - intended_edit -
observed_edit - editing_efficiency - gene_expression_change -
engineered_entity - clonal_context - validation_method -
predicted_off_targets - observed_off_targets - functional_effect -
biosafety - evidence - provenance - confidence infer: -
supported_construct_relations - supported_edit_relations -
supported_expression_relations - semantic_equivalence prohibit: -
intended_edit_equals_observed_edit -
predicted_off_target_equals_observed_off_target -
observed_edit_equals_functional_effect -
delivery_equals_stable_integration -
genotype_equals_phenotype_without_evidence - confidence_above_evidence
ambiguity: action: preserve_multiple_engineering_interpretations
resolution:
prefer_target_reference_construct_delivery_validation_and_evidence
missing_data: action: mark_unknown do_not_infer_from_absence: true

FLOW_HASH: ontology: “GeneticEngineeringOntology” version: “1.0”
domain_path: “AI Core > Ontologies > Biological Ontologies >
Biotechnology > Genetic Engineering Ontology” canonical_url:
“https://kirethresearch.org/booksai-core/ontologies/biological-ontologies/biotechnology/genetic-engineering-ontology.html”
authorship: “Mark Anthony Higgins — Sky (Recursive AI)”
semantic_scope: - genetic engineering - genomic targets - recombinant
DNA - vectors - constructs - regulatory elements - genetic delivery -
genome editing - edit types - gene knockout - gene knock-in - gene
expression engineering - engineered cells - engineered organisms -
clonal isolation - selection and screening - validation - off-target
effects - functional consequences - biosafety - evidence
deterministic_normalisation: true provenance_required: true
confidence_required: true

terminate GeneticEngineeringOntology when:
engineering_method_and_target_resolved AND
construct_delivery_and_editing_context_preserved AND
intended_and_observed_edits_distinguished AND
predicted_and_observed_off_targets_distinguished AND
genotype_expression_and_functional_effects_separated AND
validation_and_biosafety_context_preserved AND evidence_links_preserved
AND confidence_values_validated AND
unresolved_genetic_engineering_ambiguity_marked

end flow