MicroRNA Ontology

FLOW ALGEBRA
TITLE: MicroRNA Ontology
VERSION: 1.0
DATE: 2026-10-15
DOMAIN: Biological Entities / Genetic Entities
SOURCE_PAGE: https://kirethresearch.org/booksai-core/entity-graph/biological-entities/genetic-entities/microrna-ontology.html
STATUS: Domain-grounded draft; source-page contents not independently verified.
AUTHORS: Mark Higgins — Sky (Recursive AI)
SITE: https://kirethresearch.org

# 01 PURPOSE
flow "MicroRNAOntology" v1.0
purpose: represent microRNA (miRNA) entities, maturation, target recognition, regulatory outcomes and evidence with explicit biological context.

# 02 ENTITY TYPES
entity MicroRNA : NonCodingRNA
entity MIRNAGene : GenomicLocus
entity PrimaryMiRNA : RNATranscript
entity PrecursorMiRNA : HairpinRNA
entity MatureMiRNA : SmallRNA
entity PassengerStrand : SmallRNA
entity MIRNADuplex : RNAComplex
entity SeedRegion : SequenceRegion
entity TargetMRNA : MessengerRNA
entity TargetSite : SequenceRegion
entity GeneProduct : Protein
entity RISC : RibonucleoproteinComplex
entity Argonaute : Protein
entity Drosha : RNaseIIIEnzyme
entity DGCR8 : RNAProcessingProtein
entity Dicer : RNaseIIIEnzyme
entity Exportin5 : TransportProtein
entity RNAInducedSilencing : BiologicalProcess
entity ExpressionContext : BiologicalContext
entity ExperimentalEvidence : Evidence
entity RegulatoryInteraction : DirectedRelationship
entity SequenceAccession : Identifier
entity Organism : Taxon

# 03 TYPED ATTRIBUTES
MicroRNA.attributes:
  identifier: str
  preferred_name: str
  organism: Organism
  sequence_5to3: str?
  length_nt: int?
  arm: enum[5p,3p,unknown]?
  accession: SequenceAccession?
  evidence: list[ExperimentalEvidence]
  confidence: float[0,1]
TargetSite.attributes:
  transcript_accession: str
  region: enum[5UTR,CDS,3UTR,other]
  start: int?
  end: int?
  strand: str?
  genome_assembly: str?
  transcript_version: str?
RegulatoryInteraction.attributes:
  mirna: MatureMiRNA
  target: TargetMRNA
  site: TargetSite?
  outcome: enum[repression,mrna_destabilisation,translation_inhibition,context_dependent,unknown]
  context: -ExpressionContext?
  evidence: list[ExperimentalEvidence]
  confidence: float[0,1]

# 04 ONTOLOGICAL RELATIONSHIPS
MIRNAGene --transcribed_into--> PrimaryMiRNA
PrimaryMiRNA --processed_into--> PrecursorMiRNA
PrecursorMiRNA --processed_into--> MIRNADuplex
MIRNADuplex --contains--> MatureMiRNA
MIRNADuplex --may_contain--> PassengerStrand
MatureMiRNA --loaded_into--> RISC
RISC --contains--> Argonaute
MatureMiRNA --has_region--> SeedRegion
MatureMiRNA --recognises--> TargetSite
TargetSite --part_of--> TargetMRNA
RegulatoryInteraction --has_regulator--> MatureMiRNA
RegulatoryInteraction --has_target--> TargetMRNA
RegulatoryInteraction --supported_by--> ExperimentalEvidence
RegulatoryInteraction --qualified_by--> ExpressionContext

# 05 BIOGENESIS MODEL
process "CanonicalAnimalMiRNABiogenesis":
  input: MIRNAGene
  step_1: transcription -> PrimaryMiRNA
  step_2: nuclear_microprocessor(Drosha,DGCR8) -> PrecursorMiRNA
  step_3: export_via_Exportin5 -> cytoplasmic_PreMiRNA
  step_4: Dicer_processing -> MIRNADuplex
  step_5: Argonaute_loading_and_strand_selection -> RISC_with_guide
  output: MatureMiRNA_in_RISC
  note: canonical animal pathway; noncanonical pathways and other taxa may differ.

# 06 TARGET RECOGNITION
rule "SeedComplementarity":
  when: MatureMiRNA.seed_region pairs_with TargetSite
  then: candidate_target_interaction
  confidence: provisional
  caution: seed matching alone does not establish experimentally validated regulation.
rule "ContextualTargeting":
  require: transcript_isoform, cellular_expression, site_accessibility, evidence_type
  then: assess_regulatory_interaction
rule "FunctionalEffect":
  when: validated_RISC_target_binding
  then: possible_mrna_destabilisation_or_translation_repression
  caution: mechanism and magnitude depend on organism and cellular context.

# 07 CLASSIFICATION
classification:
  - canonical_miRNA
  - noncanonical_miRNA
  - intronic_miRNA
  - intergenic_miRNA
  - clustered_miRNA
  - 5p_arm_product
  - 3p_arm_product
note: categories overlap; genomic origin, pathway and mature arm are separate axes.

# 08 CONSTRAINTS AND VALIDATION
constraint "NucleotideAlphabet": sequence_5to3 uses RNA alphabet A,C,G,U, with explicit handling of ambiguity/modifications.
constraint "Identity": mature product, precursor and gene are distinct entities.
constraint "ArmNaming": 5p/3p names describe precursor arms, not fixed guide/passenger status.
constraint "TargetEvidence": predicted binding != confirmed functional repression.
constraint "SpeciesScope": avoid transferring target assertions across organisms without evidence.
constraint "CoordinateScope": coordinates require declared reference sequence and version.
constraint "ConfidenceRange": 0 <= confidence <= 1.

# 09 REASONING OPERATIONS
operation normalise_identifier(entity):
  resolve organism, database_namespace, accession_version
  preserve original_label and provenance
operation infer_candidate_target(mirna, transcript):
  evaluate seed_compatibility and transcript_context
  emit CandidateInteraction(status="predicted")
operation evaluate_validation(interaction):
  inspect reporter_assay, perturbation, binding_assay, expression_data
  distinguish direct_binding from downstream_indirect_effect
  emit EvidenceAssessment
operation trace_regulatory_path(mirna, target, context):
  follow miRNA -> RISC -> target_site -> transcript_effect
  return path_with_evidence_and_uncertainty

# 10 RECURSIVE REASONING
recursive_flow "MiRNATargetReasoning":
  input: MatureMiRNA, ExpressionContext
  stage_1: enumerate_candidate_target_sites
  stage_2: map_to_transcript_isoforms
  stage_3: check expression and accessibility
  stage_4: aggregate independent evidence
  stage_5: classify predicted_or_validated_interactions
  stage_6: trace downstream gene_product consequences
  stage_7: detect conflicting evidence and feedback loops
  termination: no_new_supported_relations OR depth_limit
  output: context_qualified_regulatory_graph

# 11 CONFIDENCE
CONFIDENCE:
  range: [0.0,1.0]
  factors:
    - experimental_validation
    - sequence_and_identifier_quality
    - tissue_or_cell_context_match
    - biological_replicates
    - independent_study_support
    - consistency_across_methods
  policy: do_not_assign_numeric_confidence_without_calibrated_method
  missing_evidence: unknown_not_zero

# 12 SEMANTIC_EQUIVALENCE
SEMANTIC_EQUIVALENCE:
  exact: same_mature_sequence_and_curated_identity_in_same_taxonomic_context
  close: alternative_database_labels_with_confirmed_cross_reference
  related: MIRNAGene_vs_PreMiRNA_vs_MatureMiRNA
  prohibited: treating_miRNA_family_members_as_identical_without_identity_evidence
  preserve: species, arm, accession, version

# 13 PROVENANCE
provenance.required:
  - source_database_or_publication
  - accession_and_version
  - organism
  - experimental_method
  - evidence_date
  - extraction_or_assertion_date
  - curator_or_pipeline
  - confidence_method

# 14 FLOW_HASH
FLOW_HASH:
  algorithm: SHA-256
  canonical_input: normalised_entities + typed_relations + evidence_refs + ontology_version
  exclude: transient_display_formatting
  purpose: integrity_and_change_detection
  implementation_note: calculate actual digest from canonical serialisation; no digest is invented here.

# 15 UPDATE_MODEL
UPDATE_MODEL:
  trigger:
    - new_miRNA_annotation
    - revised_transcript_reference
    - new_functional_evidence
    - changed_taxonomy_or_nomenclature
  actions:
    - retain_previous_version
    - reconcile_identifiers
    - revalidate_target_assertions
    - recompute_confidence_if_calibrated
    - regenerate_FLOW_HASH
    - log_provenance_and_semantic_differences
  rule: do_not_silently_overwrite_disputed_assertions

# 16 AI_CONSUMPTION
AI_CONSUMPTION:
  format: UTF-8 plain text
  entity_typing: required
  relation_direction: explicit
  evidence_status: predicted_vs_validated
  contextual_qualification: required_for_regulatory_claims
  uncertainty: preserved
  cross_links:
    - RNA Ontology
    - Messenger RNA Ontology
    - Gene Ontology
    - Genome Ontology
    - Genetic Entity Ontology
  safety: no_unsupported_diagnostic_or_therapeutic_inference

# 17 EXAMPLE (ILLUSTRATIVE, NOT AN EXPERIMENTAL CLAIM)
example:
  miRNA: miRNA_X_5p
  target: transcript_Y
  relation: candidate_binds_3UTR
  evidence_status: predicted
  confidence: unspecified
  result: hypothesis_requiring_validation

# 18 COMPLETION
output:
  ontology: MicroRNAOntology
  scope: genetic_entities
  status: structured_domain_draft
  verified_against_source_page: false
  reusable: true
END FLOW ALGEBRA