Genome Editing Ontology

flow “GenomeEditingOntology” v1.0

KIRETH SEMANTIC RESEARCH ARCHIVE

AI CORE > ONTOLOGIES > BIOLOGICAL ONTOLOGIES > BIOTECHNOLOGY > GENOME EDITING 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/genome-editing-ontology.html”

type Genome type Chromosome type Gene type Locus type Sequence type
EditingSystem type GuideRNA type Nuclease type DonorTemplate type
GeneticEdit type Cell type Organism type Observation type Evidence type
Source

relation INSTANCE_OF(entity,type) relation GENE_LOCATED_AT(gene,locus)
relation LOCUS_ON(locus,chromosome) relation TARGET_GENE(process,gene)
relation TARGET_LOCUS(process,locus) relation
TARGET_SEQUENCE(process,sequence) relation
REFERENCE_SEQUENCE(locus,sequence)

enum GenomeEditingSystem: CRISPR_CAS9 CRISPR_CAS12 CRISPR_CAS13 TALEN
ZINC_FINGER_NUCLEASE BASE_EDITOR PRIME_EDITOR RECOMBINASE MEGANUCLEASE

relation USES_EDITING_SYSTEM(process,system) relation
NUCLEASE_OF(nuclease,system) relation GUIDE_OF(guide,system)

———- GUIDE DESIGN ———-

relation GUIDE_TARGETS(guide,locus) relation
GUIDE_SEQUENCE(guide,sequence) relation
GUIDE_COMPLEMENTARY_TO(guide,sequence) relation
PAM_REQUIREMENT(system,pam) relation PAM_ADJACENT_TO(pam,locus) relation
GUIDE_EFFICIENCY_SCORE(guide,value) relation
GUIDE_SPECIFICITY_SCORE(guide,value)

constraint GUIDE_SCORE_NOT_OBSERVED_PERFORMANCE: IF
GUIDE_EFFICIENCY_SCORE(g,v) THEN
DO_NOT_INFER(observed_editing_efficiency(g,v))

———- CLEAVAGE / REPAIR ———-

relation NUCLEASE_BINDS(nuclease,locus) relation
NUCLEASE_CUTS(nuclease,locus) relation DOUBLE_STRAND_BREAK(event,locus)
relation SINGLE_STRAND_NICK(event,locus)

enum DNARepairPathway: NON_HOMOLOGOUS_END_JOINING
HOMOLOGY_DIRECTED_REPAIR MICROHOMOLOGY_MEDIATED_END_JOINING
SINGLE_STRAND_TEMPLATE_REPAIR BASE_EXCISION_REPAIR MISMATCH_REPAIR

relation REPAIR_PATHWAY_USED(event,pathway) relation
DONOR_TEMPLATE_FOR(template,event) relation
HOMOLOGY_ARM_OF(arm,template) relation REPAIR_PRODUCES(event,edit)

———- EDIT TYPES ———-

enum GenomeEditType: INSERTION DELETION SUBSTITUTION INDEL FRAMESHIFT
PRECISE_REPLACEMENT DUPLICATION INVERSION TRANSLOCATION REGULATORY_EDIT
BASE_CONVERSION

relation HAS_EDIT_TYPE(edit,type) relation EDIT_POSITION(edit,locus)
relation EDIT_REFERENCE_ALLELE(edit,sequence) relation
EDIT_ALTERNATE_ALLELE(edit,sequence) relation EDIT_LENGTH(edit,value)

relation INTENDED_EDIT(process,edit) relation
OBSERVED_EDIT(process,edit) relation ON_TARGET_EDIT(process,edit)
relation UNINTENDED_EDIT(process,edit) relation
EDITING_EFFICIENCY(process,value) relation
EDIT_ALLELE_FREQUENCY(process,edit,value)

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

———- KNOCKOUT / KNOCKIN ———-

relation KNOCKS_OUT(process,gene) relation
KNOCKS_IN(process,sequence,locus) relation
DISRUPTS_READING_FRAME(edit,gene) relation
RESTORES_READING_FRAME(edit,gene) relation
REPLACES_ALLELE(process,old_allele,new_allele)

constraint EDIT_NOT_AUTOMATIC_KNOCKOUT: IF OBSERVED_EDIT(p,e) THEN
DO_NOT_INFER(KNOCKS_OUT(p,g)) WITHOUT functional_or_frame_evidence

———- BASE / PRIME EDITING ———-

enum BaseEditingType: CYTOSINE_BASE_EDITING ADENINE_BASE_EDITING

relation HAS_BASE_EDITING_TYPE(process,type) relation
BASE_EDITOR_TARGETS(process,locus) relation
BASE_CONVERSION(process,from_base,to_base) relation
EDITING_WINDOW(process,range) relation BYSTANDER_EDIT(process,edit)

relation PRIME_EDITOR(process) relation PEG_RNA_OF(pegRNA,process)
relation PRIME_EDIT_TEMPLATE(pegRNA,sequence) relation
PRIMER_BINDING_SITE(pegRNA,sequence) relation
PRIME_EDIT_OUTCOME(process,edit)

———- DELIVERY / CONTEXT ———-

enum EditingDeliveryMethod: PLASMID_DNA MRNA RIBONUCLEOPROTEIN
VIRAL_VECTOR LIPID_NANOPARTICLE ELECTROPORATION MICROINJECTION
POLYMER_DELIVERY

relation USES_DELIVERY_METHOD(process,method) relation
DELIVERS_TO(process,cell) relation DELIVERY_EFFICIENCY(process,value)
relation TRANSIENT_EXPOSURE(process) relation
PERSISTENT_EXPRESSION(process) relation EDITED_CELL(cell) relation
EDITED_ORGANISM(organism) relation EDIT_PERFORMED_IN(process,entity)
relation CELL_TYPE_CONTEXT(process,cell_type) relation
TISSUE_CONTEXT(process,tissue) relation SOMATIC_EDIT(process) relation
GERMLINE_EDIT(process)

———- CLONAL / MOSAIC CONTEXT ———-

relation CLONAL_EDITING_RESULT(result) relation
BULK_EDITING_RESULT(result) relation CLONE_DERIVED_FROM(clone,cell)
relation CLONAL_GENOTYPE(clone,genotype) relation
POPULATION_EDIT_DISTRIBUTION(sample,distribution) relation
MOSAIC_EDIT(entity,edit) relation MOSAIC_FRACTION(entity,value) relation
CELL_SUBPOPULATION_HAS(entity,subpopulation,edit)

———- OFF-TARGET / STRUCTURAL EFFECTS ———-

relation PREDICTED_OFF_TARGET(process,locus) relation
OBSERVED_OFF_TARGET(process,locus) relation
OFF_TARGET_EDIT(process,locus,edit) relation
OFF_TARGET_FREQUENCY(process,locus,value) relation
OFF_TARGET_SIMILARITY(locus,target,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

relation LARGE_DELETION(process,edit) relation
LARGE_INSERTION(process,edit) relation
CHROMOSOMAL_REARRANGEMENT(process,edit) relation
TRANSLOCATION_EVENT(process,edit) relation
COPY_NUMBER_CHANGE(process,region,value)

———- FUNCTIONAL CONSEQUENCES ———-

relation EDIT_AFFECTS_GENE(edit,gene) relation
EDIT_AFFECTS_TRANSCRIPT(edit,transcript) relation
EDIT_AFFECTS_PROTEIN(edit,protein) relation
EDIT_AFFECTS_PATHWAY(edit,pathway) relation
EDIT_AFFECTS_TRAIT(edit,trait) relation
EXPRESSION_CHANGE(edit,gene,value) relation
FUNCTIONAL_EFFECT(edit,effect)

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

———- VALIDATION ———-

enum GenomeEditValidationMethod: PCR QPCR DIGITAL_PCR SANGER_SEQUENCING
AMPLICON_SEQUENCING TARGETED_DEEP_SEQUENCING WHOLE_GENOME_SEQUENCING
LONG_READ_SEQUENCING SOUTHERN_BLOT RNA_SEQUENCING PROTEIN_ASSAY
FUNCTIONAL_ASSAY

relation VALIDATED_BY(edit,method) relation
ON_TARGET_VALIDATED_BY(process,method) relation
OFF_TARGET_VALIDATED_BY(process,method) relation
STRUCTURAL_EDIT_VALIDATED_BY(process,method) relation
FUNCTION_VALIDATED_BY(edit,method)

———- QUALITY / BIOSAFETY ———-

relation ON_TARGET_RATE(process,value) relation
OFF_TARGET_RATE(process,value) relation PRECISE_EDIT_RATE(process,value)
relation INDEL_RATE(process,value) relation
CELL_VIABILITY_AFTER_EDITING(process,value)

enum GenomeEditingRisk: OFF_TARGET_MUTATION LARGE_DELETION TRANSLOCATION
INSERTIONAL_MUTAGENESIS MOSAICISM UNINTENDED_EXPRESSION_CHANGE
DELIVERY_TOXICITY IMMUNE_RESPONSE

relation HAS_EDITING_RISK(process,risk) relation
RISK_ASSESSMENT_OF(assessment,process) relation
MITIGATION_FOR(mitigation,risk) relation
RESIDUAL_RISK(process,risk,value)

———- 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
TARGETED_DEEP_SEQUENCING WHOLE_GENOME_SEQUENCING LONG_READ_SEQUENCING
RNA_SEQUENCING PROTEIN_ASSAY FUNCTIONAL_ASSAY OFF_TARGET_ASSAY
STRUCTURAL_VARIANT_ASSAY CLONAL_ANALYSIS CELL_VIABILITY_ASSAY
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: “genome editing” ~= “targeted alteration of
genomic sequence” “CRISPR-Cas9” ~= “RNA-guided Cas9 genome editing
system” “guide RNA” ~= “RNA molecule directing a programmable nuclease
to a target” “on-target edit” ~= “edit occurring at the intended genomic
target” “off-target edit” ~= “unintended edit outside the intended
genomic target” “knockout” ~= “genetic alteration intended to disrupt
gene function” “knock-in” ~= “targeted insertion of genetic sequence”
“base editing” ~= “programmable nucleotide conversion without
conventional double-strand cleavage” “prime editing” ~= “programmable
sequence editing using reverse-transcription-mediated copying” “editing
efficiency” ~= “fraction of analysed cells or molecules containing a
defined edit” “mosaicism” ~= “presence of genetically distinct edited
and unedited cell populations” “homology-directed repair” ~=
“template-directed repair of a DNA lesion” “non-homologous end joining”
~= “template-independent repair of DNA double-strand breaks”

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

query GENOME_EDITING_PROFILE(p): RETURN: editing_system(p)
target_gene(p) target_locus(p) guide_design(p) delivery_method(p)
repair_pathway(p) intended_edit(p) observed_edits(p)
editing_efficiency(p) off_target_events(p) mosaicism(p) validation(p)
functional_effects(p) evidence(p) confidence(p)

query EDIT_PROFILE(e): RETURN: edit_type(e) locus(e) reference_allele(e)
alternate_allele(e) allele_frequency(e) affected_gene(e)
transcript_effect(e) protein_effect(e) functional_effect(e)
validation(e)

query OFF_TARGET_PROFILE(p): RETURN: predicted_sites(p)
observed_sites(p) edit_frequencies(p) validation_methods(p)
structural_variants(p)

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

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

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

constraint REFERENCE_CONTEXT_REQUIRED: IF genetic_edit(e) THEN
PRESERVE_REFERENCE_SEQUENCE_AND_COORDINATE_CONTEXT(e)

constraint DELIVERY_CONTEXT_REQUIRED: IF genome_editing_result(r) THEN
PRESERVE_DELIVERY_METHOD_IF_KNOWN(r)

constraint CLONAL_BULK_CONTEXT_REQUIRED: IF editing_measurement(m) THEN
PRESERVE_CLONAL_OR_BULK_CONTEXT(m)

UPDATE_MODEL: on_new_editing_process(p): classify_editing_system(p)
identify_target_gene_locus_and_reference(p) identify_guide_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_coordinate_context(e) identify_edit_type(e)
preserve_clonal_or_bulk_context(e) attach_validation(e)

on_new_off_target_record(o): distinguish_predicted_from_observed_site(o)
identify_edit_if_observed(o) preserve_frequency_and_validation(o)
attach_evidence(o)

on_new_functional_record(f): identify_validated_edit(f)
preserve_expression_protein_or_trait_level(f)
distinguish_genotype_from_function(f) attach_evidence(f)

on_conflicting_genome_editing_evidence(a,b): preserve(a) preserve(b)
compare_reference_builds(a,b) compare_delivery_methods(a,b)
compare_clonal_bulk_context(a,b) compare_validation_methods(a,b)
flag_unresolved_conflict()

AI_CONSUMPTION: preferred_entity: canonical_genome_editing_entity
preserve: - editing_system - genomic_target - reference_sequence -
guide_design - pam_context - cleavage_mechanism - repair_pathway -
intended_edit - observed_edit - edit_type - editing_efficiency -
base_editing_context - prime_editing_context - delivery_method -
cell_or_organism_context - clonal_or_bulk_context - mosaicism -
predicted_off_targets - observed_off_targets - structural_variants -
functional_consequences - validation_method - biosafety - evidence -
provenance - confidence infer: - supported_target_relations -
supported_repair_relations - supported_edit_relations -
semantic_equivalence prohibit: - intended_edit_equals_observed_edit -
predicted_off_target_equals_observed_off_target -
guide_score_equals_observed_efficiency - observed_edit_equals_knockout -
genotype_equals_functional_effect -
bulk_editing_equals_clonal_genotype - confidence_above_evidence
ambiguity: action: preserve_multiple_genome_editing_interpretations
resolution:
prefer_target_reference_system_delivery_clonal_context_validation_and_evidence
missing_data: action: mark_unknown do_not_infer_from_absence: true

FLOW_HASH: ontology: “GenomeEditingOntology” version: “1.0” domain_path:
“AI Core > Ontologies > Biological Ontologies > Biotechnology > Genome
Editing Ontology” canonical_url:
“https://kirethresearch.org/booksai-core/ontologies/biological-ontologies/biotechnology/genome-editing-ontology.html”
authorship: “Mark Anthony Higgins — Sky (Recursive AI)”
semantic_scope: - genome editing - genomic targets - editing systems -
guide RNA design - PAM context - nuclease cleavage - DNA repair - edit
types - intended edits - observed edits - knockout - knock-in - base
editing - prime editing - delivery systems - edited cells and
organisms - clonal and bulk editing - mosaicism - off-target effects -
structural variation - functional consequences - validation - editing
quality - biosafety - evidence deterministic_normalisation: true
provenance_required: true confidence_required: true

terminate GenomeEditingOntology when:
editing_system_target_and_reference_resolved AND
guide_delivery_and_repair_context_preserved AND
intended_and_observed_edits_distinguished AND
predicted_and_observed_off_targets_distinguished AND
clonal_bulk_and_mosaic_context_preserved AND
genotype_and_functional_effects_distinguished AND
validation_and_biosafety_context_preserved AND evidence_links_preserved
AND confidence_values_validated AND
unresolved_genome_editing_ambiguity_marked

end flow