Cancer Biology Ontology

flow “CancerBiologyOntology” v1.0

KIRETH SEMANTIC RESEARCH ARCHIVE

AI CORE > ONTOLOGIES > BIOLOGICAL ONTOLOGIES > BIOMEDICAL SCIENCES > CANCER BIOLOGY 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/biomedical-sciences/cancer-biology-ontology.html”

type Cancer type Tumour type NeoplasticCell type Gene type Variant type
Pathway type TumourMicroenvironment type Biomarker type TherapeuticAgent
type Observation type Evidence type Source

relation INSTANCE_OF(entity,type) relation PART_OF(part,whole) relation
AFFECTS(entity,target) relation INTERACTS_WITH(a,b) relation
REGULATES(a,b) relation ASSOCIATED_WITH(a,b)

enum CancerClass: CARCINOMA SARCOMA LEUKAEMIA LYMPHOMA MYELOMA MELANOMA
GLIOMA GERM_CELL_TUMOUR NEUROENDOCRINE_TUMOUR

relation HAS_CANCER_CLASS(cancer,class) relation
PRIMARY_SITE(cancer,site) relation HISTOLOGICAL_TYPE(cancer,type)
relation MOLECULAR_SUBTYPE(cancer,subtype) relation
TUMOUR_GRADE(cancer,grade) relation TUMOUR_STAGE(cancer,stage)

———- TUMOUR EVOLUTION / GENOMICS ———-

relation TUMOUR_INITIATING_EVENT(tumour,event) relation
CLONE_OF(clone,parent) relation SUBCLONE_OF(subclone,clone) relation
CLONAL_EXPANSION(clone,event) relation
SELECTIVE_ADVANTAGE_OF(clone,trait) relation
CLONAL_FREQUENCY(tumour,clone,value) relation
TUMOUR_HETEROGENEITY(tumour,value) relation ONCOGENE_IN(gene,cancer)
relation TUMOUR_SUPPRESSOR_IN(gene,cancer) relation
ACTIVATING_VARIANT_IN(variant,gene) relation
INACTIVATING_VARIANT_IN(variant,gene) relation
GENE_AMPLIFICATION_IN(gene,cancer) relation
GENE_DELETION_IN(gene,cancer) relation FUSION_GENE_IN(fusion,cancer)
relation GENOMIC_INSTABILITY_IN(cancer,process) relation
MUTATION_BURDEN(cancer,value) relation
COPY_NUMBER_ALTERATION(cancer,region,value) relation
CHROMOSOMAL_INSTABILITY(cancer,value) relation
MICROSATELLITE_INSTABILITY(cancer,value) relation
DNA_REPAIR_DEFECT(cancer,pathway) relation
MUTATIONAL_SIGNATURE(cancer,signature)

constraint ASSOCIATED_GENE_NOT_DRIVER: IF ASSOCIATED_WITH(gene,cancer)
THEN DO_NOT_INFER(driver_gene(gene,cancer)) WITHOUT driver_evidence

———- CELL BIOLOGY / SIGNALLING ———-

relation CELL_CYCLE_DYSREGULATION(cancer,process) relation
PROLIFERATION_RATE(tumour,value) relation
CHECKPOINT_DEFECT(cancer,checkpoint) relation
REPLICATIVE_IMMORTALITY(cancer,mechanism) relation
TELOMERASE_ACTIVITY(cancer,value) relation
APOPTOSIS_RESISTANCE(cancer,mechanism) relation
CELL_SURVIVAL_PATHWAY(cancer,pathway) relation
PATHWAY_ACTIVATED_IN(pathway,cancer) relation
PATHWAY_INHIBITED_IN(pathway,cancer) relation
RECEPTOR_DYSREGULATED_IN(receptor,cancer) relation
KINASE_DYSREGULATED_IN(kinase,cancer) relation
SIGNAL_DEPENDENCY(cancer,pathway,value) relation
METABOLIC_REPROGRAMMING(cancer,process) relation
HYPOXIA_IN(tumour,value) relation ANGIOGENESIS_IN(tumour,process)
relation VESSEL_DENSITY(tumour,value)

———- MICROENVIRONMENT / IMMUNITY ———-

relation HAS_MICROENVIRONMENT(tumour,microenvironment) relation
STROMAL_CELL_IN(cell,microenvironment) relation
FIBROBLAST_IN(cell,microenvironment) relation
ENDOTHELIAL_CELL_IN(cell,microenvironment) relation
IMMUNE_CELL_IN(cell,microenvironment) relation
EXTRACELLULAR_MATRIX_IN(matrix,microenvironment) relation
CYTOKINE_IN(cytokine,microenvironment) relation
ECM_REMODELLING(tumour,process) relation MATRIX_STIFFNESS(tumour,value)
relation TUMOUR_ANTIGEN(tumour,antigen) relation
IMMUNE_RECOGNITION_OF(cell,tumour) relation
T_CELL_INFILTRATION(tumour,value) relation
IMMUNE_CHECKPOINT_EXPRESSION(tumour,checkpoint,value) relation
IMMUNE_EVASION_MECHANISM(tumour,mechanism) relation
ANTITUMOUR_RESPONSE(cell,tumour,response)

———- INVASION / METASTASIS ———-

relation INVASIVE_PHENOTYPE(tumour,phenotype) relation
EPITHELIAL_MESENCHYMAL_TRANSITION(cell,process) relation
CELL_MIGRATION_RATE(cell,value) relation CELL_INVADES(cell,tissue)
relation LOCAL_INVASION_OF(tumour,tissue) relation
METASTASISES_TO(cancer,site) relation INTRAVASATION(cell,event) relation
CIRCULATING_TUMOUR_CELL(cell) relation EXTRAVASATION(cell,event)
relation COLONISES(cell,site) relation METASTATIC_NICHE(site,niche)
relation ORGAN_TROPISM(cancer,organ)

constraint INVASION_NOT_METASTASIS: IF LOCAL_INVASION_OF(t,tissue) THEN
DO_NOT_INFER(METASTASISES_TO(t,site)) WITHOUT metastatic_evidence

———- CANCER STEM CELLS ———-

relation CANCER_STEM_CELL(cell) relation
SELF_RENEWAL_CAPACITY(cell,value) relation
TUMOUR_INITIATING_CAPACITY(cell,value) relation
STEMNESS_MARKER(cell,marker) relation STEMNESS_PATHWAY(cell,pathway)

constraint STEMNESS_MARKER_NOT_FUNCTION: IF STEMNESS_MARKER(c,m) THEN
DO_NOT_INFER(CANCER_STEM_CELL(c)) WITHOUT functional_evidence

———- BIOMARKERS / LIQUID BIOPSY ———-

enum CancerBiomarkerType: DIAGNOSTIC PROGNOSTIC PREDICTIVE MONITORING
MINIMAL_RESIDUAL_DISEASE PHARMACODYNAMIC

relation HAS_CANCER_BIOMARKER_TYPE(biomarker,type) relation
BIOMARKER_FOR(biomarker,cancer) relation
BIOMARKER_VALUE(sample,biomarker,value) relation
BIOMARKER_THRESHOLD(biomarker,value) relation
BIOMARKER_VALIDATED_IN(biomarker,cohort) relation
CIRCULATING_TUMOUR_DNA(sample,ctdna) relation
CIRCULATING_TUMOUR_CELL_IN(sample,cell) relation
TUMOUR_DERIVED_EXOSOME(sample,exosome) relation
MOLECULAR_RESIDUAL_DISEASE(sample,state)

constraint BIOMARKER_NOT_DIAGNOSIS: IF BIOMARKER_VALUE(s,b,v) THEN
DO_NOT_INFER(cancer_diagnosis(subject,c)) WITHOUT diagnostic_evidence

———- THERAPY / RESISTANCE ———-

enum CancerTherapyType: CYTOTOXIC_CHEMOTHERAPY TARGETED_THERAPY
IMMUNOTHERAPY HORMONE_THERAPY RADIOTHERAPY CELL_THERAPY GENE_THERAPY
ANTI_ANGIOGENIC_THERAPY

relation HAS_CANCER_THERAPY_TYPE(agent,type) relation
THERAPY_TARGETS(agent,target) relation
THERAPY_MECHANISM(agent,mechanism) relation
TUMOUR_RESPONSE_TO(tumour,agent,response) relation
THERAPY_SENSITIVITY(tumour,agent,value) relation
THERAPY_TOXICITY(agent,effect) relation RESISTANT_TO(tumour,agent)
relation INTRINSIC_RESISTANCE(tumour,agent) relation
ACQUIRED_RESISTANCE(tumour,agent) relation
RESISTANCE_MECHANISM(tumour,agent,mechanism) relation
RESISTANCE_VARIANT(tumour,variant) relation
BYPASS_PATHWAY(tumour,pathway)

constraint NON_RESPONSE_NOT_MECHANISM: IF non_response(tumour,agent)
THEN DO_NOT_INFER(RESISTANCE_MECHANISM(tumour,agent,m)) WITHOUT
mechanistic_evidence

———- RESPONSE / MODELS ———-

relation COMPLETE_RESPONSE(subject,cancer) relation
PARTIAL_RESPONSE(subject,cancer) relation STABLE_DISEASE(subject,cancer)
relation PROGRESSIVE_DISEASE(subject,cancer) relation
REMISSION_OF(subject,cancer) relation RECURRENCE_OF(subject,cancer)
relation MINIMAL_RESIDUAL_DISEASE(subject,state) relation
TIME_TO_PROGRESSION(subject,value) relation
PROGRESSION_FREE_SURVIVAL(population,value) relation
OVERALL_SURVIVAL(population,value)

enum CancerModelType: CELL_LINE PRIMARY_TUMOUR_CELL ORGANOID
PATIENT_DERIVED_XENOGRAFT GENETICALLY_ENGINEERED_MODEL ORGAN_ON_CHIP
COMPUTATIONAL_MODEL HUMAN_COHORT

relation HAS_CANCER_MODEL_TYPE(model,type) relation
MODEL_OF(model,cancer) relation MODEL_RECAPITULATES(model,feature)
relation MODEL_LIMITATION(model,limitation)

constraint MODEL_NOT_HUMAN_TUMOUR: IF MODEL_OF(m,c) THEN
DO_NOT_INFER(model_identical_to_human_cancer(m,c))

———- 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: HISTOPATHOLOGY IMMUNOHISTOCHEMISTRY GENOMIC
TRANSCRIPTOMIC EPIGENOMIC PROTEOMIC METABOLOMIC FLOW_CYTOMETRY IMAGING
FUNCTIONAL_ASSAY ORGANOID_STUDY ANIMAL_MODEL LIQUID_BIOPSY
CLINICAL_OBSERVATION CLINICAL_TRIAL COHORT_STUDY SYSTEMATIC_REVIEW
META_ANALYSIS 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: “cancer biology” ~= “study of molecular cellular
tissue and systemic mechanisms of neoplastic disease” “oncogene” ~=
“gene whose activation or dysregulation can promote neoplastic growth”
“tumour suppressor gene” ~= “gene whose normal function constrains
neoplastic development” “driver mutation” ~= “genetic alteration
contributing to tumour development or selective advantage” “tumour
microenvironment” ~= “non-neoplastic cellular molecular and
extracellular context surrounding tumour cells” “angiogenesis” ~=
“formation of new blood vessels” “invasion” ~= “local penetration of
surrounding tissue by tumour cells” “metastasis” ~= “spread and
establishment of tumour cells at anatomically distinct sites” “cancer
stem cell” ~= “tumour cell with experimentally supported self-renewal
and tumour-propagating capacity” “therapy resistance” ~= “reduced tumour
susceptibility to an anticancer intervention” “liquid biopsy” ~=
“analysis of tumour-derived material in body fluids” “minimal residual
disease” ~= “small amount of disease persisting after treatment”

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

query CANCER_PROFILE(c): RETURN: cancer_class(c) primary_site(c)
histology(c) molecular_subtype(c) grade(c) stage(c)
genomic_alterations(c) signalling(c) metabolism(c) microenvironment(c)
immune_interactions(c) invasion(c) metastasis(c) biomarkers(c)
therapies(c) resistance(c) evidence(c) confidence(c)

query TUMOUR_EVOLUTION_PROFILE(t): RETURN: initiating_events(t)
clones(t) subclones(t) driver_alterations(t) clonal_frequencies(t)
heterogeneity(t) selective_advantages(t)

query METASTASIS_PROFILE(c): RETURN: local_invasion(c) intravasation(c)
circulating_cells(c) extravasation(c) metastatic_sites(c)
metastatic_niches(c) organ_tropism(c)

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

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

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

constraint TUMOUR_CONTEXT_REQUIRED: IF cancer_measurement(m) THEN
PRESERVE_TUMOUR_TYPE_SITE_STAGE_AND_SAMPLE_CONTEXT(m)

constraint MODEL_CONTEXT_REQUIRED: IF cancer_model_result(r) THEN
PRESERVE_MODEL_TYPE_AND_LIMITATIONS(r)

UPDATE_MODEL: on_new_cancer_record(c):
identify_cancer_class_site_histology_and_subtype(c)
preserve_grade_and_stage(c)
attach_molecular_and_microenvironment_context(c) attach_evidence(c)
recalculate_confidence(c)

on_new_genomic_record(g): identify_tumour_and_alteration(g)
distinguish_associated_from_driver_alteration(g)
preserve_clonal_context(g) attach_evidence(g)

on_new_metastasis_record(m): identify_primary_tumour_and_site(m)
distinguish_local_invasion_from_metastasis(m)
preserve_route_and_colonisation_context(m) attach_evidence(m)

on_new_therapy_record(t): identify_tumour_agent_target_and_mechanism(t)
preserve_response_time_and_assessment_method(t)
distinguish_nonresponse_from_resistance_mechanism(t) attach_evidence(t)

AI_CONSUMPTION: preferred_entity: canonical_cancer_biology_entity
preserve: - cancer_class - primary_site - histology -
molecular_subtype - grade - stage - tumour_evolution - oncogenes -
tumour_suppressors - genomic_instability - epigenetics - cell_cycle -
apoptosis_and_survival - signalling - metabolism - hypoxia -
angiogenesis - tumour_microenvironment - immune_interactions -
invasion - metastasis - cancer_stem_cells - biomarkers - liquid_biopsy -
therapies - resistance - response - recurrence - experimental_model -
evidence - provenance - confidence infer: - supported_clonal_relations -
supported_driver_relations - supported_metastatic_relations -
semantic_equivalence prohibit: - association_equals_driver_status -
local_invasion_equals_metastasis -
stemness_marker_equals_cancer_stem_cell - biomarker_equals_diagnosis -
nonresponse_equals_demonstrated_resistance_mechanism -
model_equals_human_tumour - confidence_above_evidence ambiguity: action:
preserve_multiple_cancer_biology_interpretations resolution:
prefer_tumour_type_site_stage_sample_model_method_and_evidence
missing_data: action: mark_unknown do_not_infer_from_absence: true

FLOW_HASH: ontology: “CancerBiologyOntology” version: “1.0” domain_path:
“AI Core > Ontologies > Biological Ontologies > Biomedical Sciences >
Cancer Biology Ontology” canonical_url:
“https://kirethresearch.org/booksai-core/ontologies/biological-ontologies/biomedical-sciences/cancer-biology-ontology.html”
authorship: “Mark Anthony Higgins — Sky (Recursive AI)”
semantic_scope: - cancer classification - tumour evolution - oncogenes -
tumour suppressors - genomic instability - epigenetics - proliferation -
cell survival - signalling - metabolism - hypoxia - angiogenesis -
tumour microenvironment - immune interactions - invasion - metastasis -
cancer stem cells - biomarkers - liquid biopsy - anticancer therapy -
therapy resistance - response - recurrence - experimental models -
evidence deterministic_normalisation: true provenance_required: true
confidence_required: true

terminate CancerBiologyOntology when:
cancer_class_site_histology_subtype_grade_and_stage_resolved AND
associated_and_driver_alterations_distinguished AND
clonal_evolution_and_genomic_context_preserved AND
local_invasion_and_metastasis_distinguished AND
biomarker_and_diagnostic_context_distinguished AND
treatment_nonresponse_and_resistance_mechanism_distinguished AND
model_and_human_tumour_context_distinguished AND
evidence_links_preserved AND confidence_values_validated AND
unresolved_cancer_biology_ambiguity_marked

end flow