NIF Phenotype core
type: Ontology
comment: This is the core set of predicates used to model phenotypes and the parent class for phenotypes.

hasAdaptationPhenotype
type: AsymmetricProperty
type: IrreflexiveProperty
type: ObjectProperty
sub property of: hasElectrophysiologicalPhenotype
comment: currently spo ephys since it describes the changes in phys in response to repeated stimulation

hasAnatomicalSystemPhenotype
type: AsymmetricProperty
type: IrreflexiveProperty
type: ObjectProperty
definition: Expresses a relationship between a neuron type and some anatomical criteria, such as being located in a particular system. Note that this NOT a subPropertOf hasLocationPhenotype.
sub property of: hasPhenotype
comment: This is used to differentiate things like parasympathetic preganglionic from raw hasPhenotype. This can be used in cases where the meaning is clear to the domain experts, but has not been fully formalized.

hasAxonLeadingToSensorySubcellularElementIn
type: AsymmetricProperty
type: IrreflexiveProperty
type: ObjectProperty
sub property of: hasAxonLocatedIn
comment: a weak property that only asserts that distally there is expected to be at least one case of a hasAxonSensorySubcellularElementIn region in the partial order

hasAxonLocatedIn
type: AsymmetricProperty
type: IrreflexiveProperty
type: ObjectProperty
sub property of: hasProcessLocatedIn

hasAxonMorphologicalPhenotype
type: AsymmetricProperty
type: IrreflexiveProperty
type: ObjectProperty
sub property of: hasMorphologicalPhenotype
comment: not clear whether this should be subPropertyOf hasMorphologicalPhenotype

hasAxonPhenotype
type: ObjectProperty
definition: Expresses a relationship between a neuron type and some phenotype of its axon.
sub property of: hasPhenotype
comment: Use to provide clarity about where a generic phenotype is attached in the event that the object is not qualified. The alternative is to precompose the subcompartments e.g. SmallSomaPhenotype and SmallAxonPhenotype.

hasAxonPresynapticElementIn
type: ObjectProperty
sub property of: hasAxonLocatedIn
sub property of: hasPresynapticElementIn

hasAxonSensorySubcellularElementIn
type: AsymmetricProperty
type: IrreflexiveProperty
type: ObjectProperty
sub property of: hasAxonLeadingToSensorySubcellularElementIn
sub property of: hasSensorySubcellularElementIn

hasAxonSensorySubcellularStructure
type: AsymmetricProperty
type: IrreflexiveProperty
type: ObjectProperty
definition: Expresses a relationship between a neuron and an axon sensory subcellular structure. Should be used to describe e.g. nerve ending types.
sub property of: hasAxonMorphologicalPhenotype

hasBiologicalSex
type: AsymmetricProperty
type: IrreflexiveProperty
type: ObjectProperty
definition: Expresses a relationship between a neuron type and a biological sex. This should be used when a neuron type has been observed in a specific sex.
sub property of: hasPhenotype

hasCircuitRolePhenotype
type: AsymmetricProperty
type: IrreflexiveProperty
type: ObjectProperty
sub property of: hasPhenotype
comment: needs work

hasClassificationPhenotype
type: AsymmetricProperty
type: IrreflexiveProperty
type: ObjectProperty
definition: Expresses a relationship between a neuron type and an opaque symbol that is used by experts to distinguish subtypes.
sub property of: hasPhenotype
comment: Use this when numbers or letters have been assigned to disambiguate naming.

hasComputedMolecularPhenotype
type: AsymmetricProperty
type: IrreflexiveProperty
type: ObjectProperty
definition: Expresses a relationship between a neuron type and a type computed from only molecular data.
sub property of: hasComputedPhenotype
sub property of: hasMolecularPhenotype

hasComputedMolecularPhenotypeFromDNA
type: AsymmetricProperty
type: IrreflexiveProperty
type: ObjectProperty
definition: Expresses a relationship between a neuron type and a type computed from only DNA data (e.g. epigenetics data).
sub property of: hasComputedMolecularPhenotype

hasComputedMolecularPhenotypeFromProtein
type: AsymmetricProperty
type: IrreflexiveProperty
type: ObjectProperty
definition: Expresses a relationship between a neuron type and a type computed from only Protein expression data.
sub property of: hasComputedMolecularPhenotype

hasComputedMolecularPhenotypeFromRNA
type: AsymmetricProperty
type: IrreflexiveProperty
type: ObjectProperty
definition: Expresses a relationship between a neuron type and a type computed from only RNA expression data.
sub property of: hasComputedMolecularPhenotype

hasComputedPhenotype
type: AsymmetricProperty
type: IrreflexiveProperty
type: ObjectProperty
definition: Expresses a relationship between a neuron type and a type computed from some combination of primary data types.
sub property of: hasPhenotype

hasConnectionDeterminedByCellFilling
type: ObjectProperty
sub property of: hasForwardConnectionPhenotype

hasConnectionDeterminedByElectronMicroscopy
type: ObjectProperty
sub property of: hasForwardConnectionPhenotype
comment: traditionally harder to get granular types here?

hasConnectionDeterminedByElectrophysiology
type: ObjectProperty
sub property of: hasForwardConnectionPhenotype
comment: anything from estim to in vitro slice

hasConnectionDeterminedByPharmacology
type: ObjectProperty
sub property of: hasConnectionDeterminedByElectrophysiology
comment: specificity of connections often require pharm

hasConnectionDeterminedBySynapticPhysiology
type: ObjectProperty
sub property of: hasConnectionDeterminedByElectrophysiology
comment: ephys or ca2+

hasConnectionDeterminedByViralTracing
type: ObjectProperty
sub property of: hasForwardConnectionPhenotype
comment: transsynaptic?

hasConnectionPhenotype
type: ObjectProperty
type: SymmetricProperty
definition: Expresses a relationship between a neuron type and a neuron type or a neuron type and a subcompartment of a neuron type some members are connected with eachother.
sub property of: hasPhenotype
comment: Absent a specific subcompartment we can only infer hasProjectionPhenotype at the granularity of soma + dendrite location. NOTE: This relationship does not imply direction. If you need direction please choose a subproperty.

hasDendriteLocatedIn
type: AsymmetricProperty
type: IrreflexiveProperty
type: ObjectProperty
sub property of: hasProcessLocatedIn

hasDendriteMorphologicalPhenotype
type: AsymmetricProperty
type: IrreflexiveProperty
type: ObjectProperty
definition: Expresses a relationship between a neuron and a dendrite phenotype. This should be used when a neuron type is described by the morphology of its dendrites.
sub property of: hasMorphologicalPhenotype
comment: not clear whether this should be subPropertyOf hasMorphologicalPhenotype

hasDendritePhenotype
type: ObjectProperty
definition: Expresses a relationship between a neuron type and some phenotype of its dendrite.
sub property of: hasPhenotype
comment: Use to provide clarity about where a generic phenotype is attached in the event that the object is not qualified. The alternative is to precompose the subcompartments e.g. SmallSomaPhenotype and SmallAxonPhenotype.

hasDendriteSensorySubcellularElementIn
type: AsymmetricProperty
type: IrreflexiveProperty
type: ObjectProperty
sub property of: hasDendriteLocatedIn
sub property of: hasSensorySubcellularElementIn

hasDevelopmentalStage
type: AsymmetricProperty
type: IrreflexiveProperty
type: ObjectProperty
definition: Expresses a relationship between a neuron type and a developmental stage. This should be used when a neuron type has been observed during a developmental stage.
sub property of: hasPhenotype

hasDevelopmentalStructure
type: ObjectProperty
definition: Expresses a relationship between a neuron type and a developmental cell population. This should be used when a neuron develops from an identified developmental anatomical entity.
sub property of: hasPhenotype
comment: needs work

hasDevelopmentalType
type: ObjectProperty
definition: Expresses a relationship between a neuron type and a developmental cell population. This should be used when a neuron develops from an identified developmental cell type.
sub property of: hasPhenotype

hasDriverExpressionConstitutivePhenotype
type: AsymmetricProperty
type: IrreflexiveProperty
type: ObjectProperty
sub property of: hasDriverExpressionPhenotype

hasDriverExpressionInducedPhenotype
type: AsymmetricProperty
type: IrreflexiveProperty
type: ObjectProperty
sub property of: hasDriverExpressionPhenotype
comment: Use for things like cre-ER

hasDriverExpressionPhenotype
type: AsymmetricProperty
type: IrreflexiveProperty
type: ObjectProperty
sub property of: hasExpressionPhenotype

hasElectrophysiologicalPhenotype
type: AsymmetricProperty
type: IrreflexiveProperty
type: ObjectProperty
definition: Expresses a relationship between a neuron type and an electrophysiological phenotype concept. This should be used when a neuron type is described using a high level electrophysiological concept class.
sub property of: hasPhenotype

hasExperimentalPhenotype
type: AsymmetricProperty
type: IrreflexiveProperty
type: ObjectProperty
definition: Expresses a relationship between a neuron and an experimental condition. This should be used when a neuron type is described by some experimental condition or functional designation.
sub property of: hasPhenotype
comment: This needs a better name. It is clear what it means when you see examples of the usage.

hasExpressionPhenotype
type: AsymmetricProperty
type: IrreflexiveProperty
type: ObjectProperty
definition: Expresses a relationship between a neuron type and a gene type including any gene products.
sub property of: hasMolecularPhenotype
comment: This may also include the products of molecular synthesis pathways that are indirectly supported by genes, however it seems likely that that relationship should not be though of as an expression phenotype.

hasForwardConnectionPhenotype
type: AsymmetricProperty
type: IrreflexiveProperty
type: ObjectProperty
sub property of: hasConnectionPhenotype
inverse of: hasReverseConnectionPhenotype
comment: can be inferred from symmetric connection + projects to

hasFunctionalCircuitRolePhenotype
type: AsymmetricProperty
type: IrreflexiveProperty
type: ObjectProperty
definition: Expresses a relationship between a neuron and the immediate effect that it has on post synaptic cells. This is usually either excitatory or inhibitory.
sub property of: hasPhenotype
comment: this is currently a subproperty of hasPhenotype because we need to work out the relationship between circuit role and projection phenotype

hasFunctionalPhenotype
type: AsymmetricProperty
type: IrreflexiveProperty
type: ObjectProperty
definition: Expresses a relationship between a neuron and some external property such as high level sensory function.
sub property of: hasPhenotype
comment: This should probably be equivalent to hasExperimentalPhenotype, however experimental phenotype implies that the value was actually determined experimentally for a given individual which functional does not necessarily imply.

hasInstanceInSpecies
type: AsymmetricProperty
type: IrreflexiveProperty
type: ObjectProperty
definition: Expresses a relationship between a neuron type and a species. This should be used when a neuron type has been observed in a specific species.
sub property of: hasPhenotype
comment: should rarely be used, even if dealing with evidence based models because it is an extremely weak assertion, possibly rename to hasBeenObservedInAtLeastOneIndividualInSpecies or something like that

hasInstanceInTaxon
type: AsymmetricProperty
type: IrreflexiveProperty
type: ObjectProperty
definition: Expresses a relationship between a neuron type and a taxon. When dealing with both EBMs and CUTs this is the predicate that should be used.
sub property of: hasInstanceInSpecies
comment: this is the weakest assertion we have available at a taxon level, hasInstanceInSpecies is even weaker since it does not propagage

hasLayerLocationPhenotype
type: AsymmetricProperty
type: IrreflexiveProperty
type: ObjectProperty
definition: Expresses a relationship between a neuron type and a laminar brain region.
sub property of: hasLocationPhenotype
comment: May need hasSomaLayerLocation or something, do we really even need this?? if axioms are missing in parcellation schemes and uberon then it should be easy enough to add them, or at least we won't get disjointness issues because layers of cortex are orthogonal to parts of cortex (eg) and thus we shouldnt get reasoning errors

hasLocationPhenotype
type: AsymmetricProperty
type: IrreflexiveProperty
type: ObjectProperty
definition: Expresses a relationship between a neuron type and a brain region or brain parcel. This is a superProperty and should not be used directly.
sub property of: hasPhenotype
comment: This property should not be used directly.

hasMolecularPhenotype
type: AsymmetricProperty
type: IrreflexiveProperty
type: ObjectProperty
definition: Expresses a relationship between a neuron type and a molecule type, a gene type, or a gene product type.
sub property of: hasPhenotype
comment: This can be used for detection of the molecule or gene by any means.

hasMorphologicalPhenotype
type: AsymmetricProperty
type: IrreflexiveProperty
type: ObjectProperty
definition: Expresses a relationship between a neuron type and a morphological phenotype concept. This should be used when a neuron type is described using a high level morphological concept class.
sub property of: hasPhenotype

hasNeurotransmitterPhenotype
type: AsymmetricProperty
type: IrreflexiveProperty
type: ObjectProperty
definition: Expresses a relationship between a neuron type and a neurotransmitter that is released from vesicles contained within neurons of that neuron type.
sub property of: hasMolecularPhenotype
comment: includes small molecule and peptide, not entirely sure if we need this one, we do because expression and release are not 1:1

hasNucleicAcidExpressionPhenotype
type: AsymmetricProperty
type: IrreflexiveProperty
type: ObjectProperty
sub property of: hasExpressionPhenotype
comment: This should be used for detection of RNAs that code for proteins which may or may not have been detected directly.

hasPhenotype
type: ObjectProperty
inverse of: phenotypeOf

hasPhenotypeModifier
type: AsymmetricProperty
type: IrreflexiveProperty
type: ObjectProperty
definition: Expresses a restriction that modifies all phenotypes associated with a neuron type or a logical phenotype, only meaningful when used inside of owl:intersectionOf

hasPresynapticElementIn
type: AsymmetricProperty
type: IrreflexiveProperty
type: ObjectProperty
sub property of: hasProcessLocatedIn
comment: DO NOT USE, AMBIGUOUS! projectsTo does not work because of dendrodentritic synapses, for the same reason this cannot be a subProperty of hasAxonLocatedIn

hasPresynapticTerminalsIn
type: ObjectProperty
sub property of: hasPresynapticElementIn
comment: DO NOT USE, AMBIGUOUS! Are there cases where there are boutons that form on dendrites?

hasProcessLocatedIn
type: AsymmetricProperty
type: IrreflexiveProperty
type: ObjectProperty
sub property of: hasLocationPhenotype

hasProjectionLaterality
type: AsymmetricProperty
type: IrreflexiveProperty
type: ObjectProperty
definition: Expresses a relationship between a neuron type and whether the target region it projects to is on the same, opposite, or both sides of the brain.
sub property of: hasProjectionPhenotype
comment: ispilateral, contralateral, and bilateral are kind of like cortico thalamic but they are lifted to an invariant form that doesn’t care about the exact starting side, unilateral is the union of ipsi and contra but I’m fairly certain that unilateral should never be reported because it is ambiguous, this is primarily a convenience relation for neurons that have a single projection laterality, however there are plenty of examples where there are neurons that project to two different regions one of which is ipsi and the other of which is contra, those cases require the composition to happen on the object of the restriction, so you wind up with has projection phenotype some ipsilateral region, otherwise all our definitions are consistent with bilateral and unilateral projections, which is something we will probably have to fix, right now we are using the PATO laterality terms but the modelling isn’t really what we want because we need to have ipsilateral disjoint from contralateral and disjoint from bilateral

hasProjectionPhenotype
type: AsymmetricProperty
type: IrreflexiveProperty
type: ObjectProperty
definition: Expresses a relationship between a neuron type and a brain region that said neuron type sends axons to.
sub property of: hasPhenotype
comment: this might be clearer than hasCircuitRole but might confuse with projectsTo or the like, excitatory/inhibitory shouldn't be handled here? The way that projection vs intrinsic is modelled relates whether axons leave the brain region that contains the soma or not, this is not fully modelled at the moment

hasProteinExpressionPhenotype
type: AsymmetricProperty
type: IrreflexiveProperty
type: ObjectProperty
sub property of: hasExpressionPhenotype

hasReporterExpressionPhenotype
type: AsymmetricProperty
type: IrreflexiveProperty
type: ObjectProperty
sub property of: hasExpressionPhenotype

hasReverseConnectionPhenotype
type: AsymmetricProperty
type: IrreflexiveProperty
type: ObjectProperty
sub property of: hasConnectionPhenotype
inverse of: hasForwardConnectionPhenotype

hasSensorySubcellularElementIn
type: AsymmetricProperty
type: IrreflexiveProperty
type: ObjectProperty
definition: Expresses a relationship between a neuron and a nervous system region where that neuron has a part which is involved in the direct detection of sensory stimuli.
sub property of: hasLocationPhenotype
comment: This is the equivalent of axon terminals for sensory dendrites in the peripheral nervous system. Not 100% sure on the modeling, but some mechanosensory neurons this would be the anatomcal region(s) where the Pacinian corpuscle are located.

hasSmallMoleculePhenotype
type: AsymmetricProperty
type: IrreflexiveProperty
type: ObjectProperty
definition: Expresses a relationship between a neuron and a small molecule that is the product of some molecular pathway that may or may not be expressed in the neuron in question.
sub property of: hasMolecularPhenotype
comment: This would probably be used to indicate the detection of the machinery for the synthesis pathway. If just the molecule is detected then hasMolecularPhenotype should be used since expression cannot be inferred (for neurotransmitters).

hasSomaLocatedIn
type: AsymmetricProperty
type: IrreflexiveProperty
type: ObjectProperty
sub property of: hasLocationPhenotype

hasSomaLocatedInLayer
type: ObjectProperty
sub property of: hasLayerLocationPhenotype
sub property of: hasSomaLocatedIn

hasSomaLocationLaterality
type: ObjectProperty
sub property of: hasSomaLocatedIn

hasSomaPhenotype
type: ObjectProperty
definition: Expresses a relationship between a neuron type and some phenotype of its soma.
sub property of: hasPhenotype
comment: Use to provide clarity about where a generic phenotype is attached in the event that the object is not qualified. The alternative is to precompose the subcompartments e.g. SmallSomaPhenotype and SmallAxonPhenotype.

hasTaxonRank
type: AsymmetricProperty
type: IrreflexiveProperty
type: ObjectProperty
definition: Expresses a relationship between a neuron type and a taxon. This should be used when a neuron type is thought to have been present in the last common ancestor of the taxon.
sub property of: hasInstanceInTaxon
comment: note that this is a subPropertyOf hasInstanceInTaxon NOT the other way around, aka isAncestralInTaxon, even stronger claim than instance and propagates downward implying that instances were present in all members except those specifically marked (which owl can't really support)

hasThresholdPhenotype
type: AsymmetricProperty
type: IrreflexiveProperty
type: ObjectProperty
sub property of: hasFunctionalPhenotype
comment: currently spo functional, I think this is general to any external metric where the response of a neuron behaves non-linearly across a set threshold

isMemberOfCircuit
type: AsymmetricProperty
type: IrreflexiveProperty
type: ObjectProperty
definition: Expresses a relationship between a neuron type and a circuit type that the neuron type is a member of. Implies that individual neurons of that type each have at least one forward or reverse connection with some other member of that circuit type.
sub property of: RO_0002350

phenotypeCooccuresWith
type: ObjectProperty
definition: Expresses a relationship between a phenotype and a phenotype. This should be used when two phenotypes commonly cooccure.
comment: this is not the right way to pull this off, need something akin to disjointness

phenotypeObservedInBrainRegion
type: ObjectProperty
definition: Expresses a relationship between a phenotype and a brain region. This should be used when a neuron phenotype is observed in specific brain regions.
comment: existential not universal

phenotypeOf
type: ObjectProperty
comment: of course this can never be universal, so is mostly useful for the python representation

receivesProjectionFrom
type: AsymmetricProperty
type: IrreflexiveProperty
type: ObjectProperty
definition: Expresses a relationship between a neuron type and a brain region where said neuron type has a reverse connection phenotype with some neuron type that has its soma located in said brain region.
sub property of: hasPhenotype
comment: this is essentially hasReverseProjectionPhenotype, however, unlike for connection phenotypes where forward and reverse are not ambiguous, a reverse projection is a confusing concept and thus not used

Phenotype
type: Class
definition: A Phenotype is a binary property of a biological entity. Phenotypes are derived from measurements made on the subject of interest. While Phenotype is not currently placed within the BFO hierarchy, if we were to place it, it would fall under BFO:0000016 -> disposition, since these phenotypes are contingent on the experimental conditions under which measurements were made and are NOT qualities. For consideration: in theory this would mean that disjointness does not make sense, even for things that would seem to be obviously disjoint such as Accommodating and Non-Accommodating. However, this information can still be captured on a subject by subject basis by asserting that for this particular entity, coocurrance of phenotypes is not possible. This still leaves the question of whether the class of biological entities that correspond to the bag of phenotypes is implicitly bounded/limited only to the extrinsic and unspecified experimental conditions, some of which are not and cannot be included in a bag of phenotypes. The way to deal with this when we want to include 2 'same time' disjoint phenotypes, is to use a logical phenotype to wrap them with an auxiliary variable that we think accounts for the difference.