CRISPR Ontology

flow “CRISPROntology” v1.0

KIRETH SEMANTIC RESEARCH ARCHIVE

AI CORE > ONTOLOGIES > BIOLOGICAL ONTOLOGIES > BIOTECHNOLOGY > CRISPR 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/crispr-ontology.html”

type CRISPRSystem type CasProtein type GuideRNA type PAM type
TargetSequence type Gene type Locus type GeneticEdit type DonorTemplate
type Cell type Organism type Observation type Evidence type Source

relation INSTANCE_OF(entity,type) relation
COMPONENT_OF(component,system) relation TARGETS(entity,target) relation
BINDS_TO(entity,target) relation CLEAVES(entity,target) relation
MODIFIES(process,target) relation PRODUCES(process,outcome)

enum CRISPRClass: CLASS_1 CLASS_2

enum CRISPRType: TYPE_I TYPE_II TYPE_III TYPE_IV TYPE_V TYPE_VI

relation HAS_CRISPR_CLASS(system,class) relation
HAS_CRISPR_TYPE(system,type) relation HAS_EFFECTOR(system,cas_protein)

———- CAS / GUIDE / PAM ———-

enum CasEffector: CAS9 CAS12A CAS12B CAS13A CAS13B CAS13D DCAS9
NICKASE_CAS9

relation HAS_CAS_EFFECTOR(system,effector) relation
CAS_REQUIRES_PAM(protein,pam) relation CAS_REQUIRES_GUIDE(protein,guide)
relation GUIDE_OF(guide,system) relation GUIDE_SEQUENCE(guide,sequence)
relation GUIDE_TARGETS(guide,target) relation
GUIDE_COMPLEMENTARY_TO(guide,target_sequence) relation
GUIDE_EFFICIENCY_SCORE(guide,value) relation
GUIDE_SPECIFICITY_SCORE(guide,value) relation PAM_SEQUENCE(pam,sequence)
relation PAM_ADJACENT_TO(pam,target) relation PAM_RECOGNISED_BY(pam,cas)
relation PAM_ORIENTATION(pam,orientation)

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

———- TARGET RECOGNITION / CLEAVAGE ———-

relation TARGET_GENE(process,gene) relation TARGET_LOCUS(process,locus)
relation TARGET_SEQUENCE_OF(target,sequence) relation
PROTOSPACER_OF(sequence,target) relation R_LOOP_FORMS_AT(system,target)
relation SEED_REGION_OF(sequence,guide) relation
MISMATCH_BETWEEN(guide,target,position) relation
CAS_BINDS_TARGET(cas,target) relation CAS_CLEAVES_TARGET(cas,target)
relation CLEAVAGE_POSITION(event,position) relation
DOUBLE_STRAND_BREAK(event,locus) relation
SINGLE_STRAND_NICK(event,locus) relation RNA_CLEAVAGE(event,rna)

———- DNA REPAIR / EDITS ———-

enum RepairPathway: NON_HOMOLOGOUS_END_JOINING HOMOLOGY_DIRECTED_REPAIR
MICROHOMOLOGY_MEDIATED_END_JOINING SINGLE_STRAND_TEMPLATE_REPAIR

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

enum CRISPREditType: INSERTION DELETION INDEL SUBSTITUTION FRAMESHIFT
PRECISE_REPLACEMENT REGULATORY_EDIT BASE_CONVERSION

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) 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 CRISPR_KNOCKOUT(process,gene) relation
CRISPR_KNOCKIN(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(CRISPR_KNOCKOUT(p,g)) WITHOUT functional_or_frame_evidence

———- BASE / PRIME EDITING ———-

enum CRISPRBaseEditor: CYTOSINE_BASE_EDITOR ADENINE_BASE_EDITOR

relation USES_BASE_EDITOR(process,editor) relation
BASE_EDITOR_CONTAINS(editor,cas) relation
BASE_CONVERSION(process,from_base,to_base) relation
EDITING_WINDOW(process,range) relation BYSTANDER_EDIT(process,edit)

relation PRIME_EDITING_PROCESS(process) relation
PRIME_EDITOR_CONTAINS(editor,cas_nickase) relation
PEG_RNA_OF(pegRNA,process) relation PRIME_EDIT_TEMPLATE(pegRNA,sequence)
relation PRIMER_BINDING_SITE(pegRNA,sequence) relation
PRIME_EDIT_OUTCOME(process,edit)

———- CRISPRI / CRISPRA / RNA TARGETING ———-

enum CRISPRRegulationMode: CRISPRI CRISPRA

relation HAS_REGULATION_MODE(process,mode) relation
DCAS_BINDS(dcas,locus) relation CRISPRI_REPRESSES(process,gene) relation
CRISPRA_ACTIVATES(process,gene) relation
EXPRESSION_CHANGE(process,gene,value) relation CAS13_TARGETS(cas13,rna)
relation GUIDE_TARGETS_RNA(guide,rna) relation
RNA_KNOCKDOWN(process,rna)

———- DELIVERY / BIOLOGICAL CONTEXT ———-

enum CRISPRDeliveryMethod: 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 CRISPR_EDITED_CELL(cell)
relation CRISPR_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) relation CLONAL_RESULT(result) relation
BULK_RESULT(result)

———- OFF-TARGET / STRUCTURAL OUTCOMES ———-

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_MISMATCH_COUNT(locus,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 TRANSLOCATION_EVENT(process,edit)
relation CHROMOSOMAL_REARRANGEMENT(process,edit) relation
MOSAIC_EDIT(entity,edit) relation MOSAIC_FRACTION(entity,value)

———- FUNCTION / VALIDATION ———-

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 FUNCTIONAL_EFFECT(edit,effect)

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

enum CRISPRValidationMethod: PCR QPCR DIGITAL_PCR SANGER_SEQUENCING
AMPLICON_SEQUENCING TARGETED_DEEP_SEQUENCING WHOLE_GENOME_SEQUENCING
LONG_READ_SEQUENCING RNA_SEQUENCING PROTEIN_ASSAY FUNCTIONAL_ASSAY
OFF_TARGET_ASSAY

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

———- PERFORMANCE / SAFETY ———-

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 CRISPRRisk: OFF_TARGET_MUTATION LARGE_DELETION TRANSLOCATION
MOSAICISM UNINTENDED_EXPRESSION_CHANGE DELIVERY_TOXICITY IMMUNE_RESPONSE

relation HAS_CRISPR_RISK(process,risk) relation
RISK_ASSESSMENT_OF(assessment,process) relation
MITIGATION_FOR(mitigation,risk)

———- 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: GUIDE_DESIGN_ANALYSIS 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: “CRISPR” ~= “clustered regularly interspaced short
palindromic repeats associated system” “CRISPR-Cas” ~= “RNA-guided
CRISPR-associated effector system” “Cas9” ~= “CRISPR-associated protein
9” “guide RNA” ~= “RNA molecule directing a CRISPR effector to a target”
“sgRNA” ~= “single guide RNA” “PAM” ~= “protospacer adjacent motif”
“protospacer” ~= “target sequence complementary to a CRISPR guide”
“CRISPR knockout” ~= “CRISPR-mediated genetic alteration intended to
disrupt gene function” “CRISPR knock-in” ~= “CRISPR-mediated targeted
insertion of sequence” “CRISPRi” ~= “CRISPR interference” “CRISPRa” ~=
“CRISPR activation” “base editing” ~= “CRISPR-derived programmable
nucleotide conversion” “prime editing” ~= “CRISPR-derived programmable
reverse-transcription-mediated sequence editing” “off-target edit” ~=
“unintended CRISPR-associated edit outside the intended target”

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

query CRISPR_PROFILE(p): RETURN: crispr_system(p) cas_effector(p)
guide_rna(p) pam(p) target_gene(p) target_locus(p) delivery_method(p)
cleavage_or_regulation_mode(p) repair_pathway(p) intended_edit(p)
observed_edits(p) editing_efficiency(p) off_target_events(p)
validation(p) functional_effects(p) evidence(p) confidence(p)

query GUIDE_PROFILE(g): RETURN: guide_sequence(g) target(g) pam(g)
efficiency_score(g) specificity_score(g) mismatches(g)
observed_performance(g)

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

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

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

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

constraint TARGET_CONTEXT_REQUIRED: IF crispr_edit(e) THEN
PRESERVE_TARGET_REFERENCE_AND_PAM_CONTEXT(e)

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

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

UPDATE_MODEL: on_new_crispr_process(p):
classify_crispr_system_and_effector(p) identify_guide_pam_and_target(p)
preserve_delivery_context(p)
identify_cleavage_regulation_or_editing_mode(p) attach_evidence(p)
recalculate_confidence(p)

on_new_crispr_edit(e): distinguish_intended_from_observed_edit(e)
preserve_target_reference_and_pam_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)
preserve_mismatch_and_frequency_context(o) attach_validation(o)
attach_evidence(o)

on_new_functional_record(f):
identify_validated_edit_or_regulatory_change(f)
distinguish_genotype_expression_and_function(f) attach_evidence(f)

on_conflicting_crispr_evidence(a,b): preserve(a) preserve(b)
compare_crispr_effectors(a,b) compare_guides_and_pams(a,b)
compare_delivery_methods(a,b) compare_validation_methods(a,b)
flag_unresolved_conflict()

AI_CONSUMPTION: preferred_entity: canonical_crispr_entity preserve: -
crispr_class - crispr_type - cas_effector - guide_rna - pam_context -
target_sequence - cleavage_context - repair_pathway - intended_edit -
observed_edit - knockout_or_knockin_context - base_editing_context -
prime_editing_context - crispri_crispra_context -
rna_targeting_context - delivery_method - cell_or_organism_context -
clonal_or_bulk_context - off_target_context - structural_outcomes -
mosaicism - functional_consequences - validation - biosafety -
evidence - provenance - confidence infer: - supported_target_relations -
supported_crispr_component_relations - supported_edit_relations -
semantic_equivalence prohibit: -
guide_score_equals_observed_performance -
intended_edit_equals_observed_edit -
predicted_off_target_equals_observed_off_target -
observed_edit_equals_gene_knockout - genotype_equals_functional_effect -
bulk_result_equals_clonal_genotype - confidence_above_evidence
ambiguity: action: preserve_multiple_crispr_interpretations resolution:
prefer_system_effector_guide_pam_target_delivery_validation_and_evidence
missing_data: action: mark_unknown do_not_infer_from_absence: true

FLOW_HASH: ontology: “CRISPROntology” version: “1.0” domain_path: “AI
Core > Ontologies > Biological Ontologies > Biotechnology > CRISPR
Ontology” canonical_url:
“https://kirethresearch.org/booksai-core/ontologies/biological-ontologies/biotechnology/crispr-ontology.html”
authorship: “Mark Anthony Higgins — Sky (Recursive AI)”
semantic_scope: - CRISPR systems - CRISPR classes and types - Cas
effectors - guide RNA - PAM recognition - target recognition - nuclease
cleavage - DNA repair - edit outcomes - knockout - knock-in - base
editing - prime editing - CRISPR interference - CRISPR activation - RNA
targeting - delivery - biological context - off-target effects -
structural outcomes - mosaicism - functional consequences - validation -
performance - biosafety - evidence deterministic_normalisation: true
provenance_required: true confidence_required: true

terminate CRISPROntology when:
crispr_system_effector_guide_pam_and_target_resolved AND
cleavage_regulation_or_editing_mode_preserved AND
intended_and_observed_edits_distinguished AND
predicted_and_observed_off_targets_distinguished AND
clonal_bulk_and_mosaic_context_preserved AND
genotype_expression_and_functional_effects_distinguished AND
validation_and_biosafety_context_preserved AND evidence_links_preserved
AND confidence_values_validated AND unresolved_crispr_ambiguity_marked

end flow