DIKB evidence ontology.owl
type: Ontology
comment: Authors: Richard D. Boyce, PhD*, Carol Collins**, John Horn**, Ira Kalet**, John Gennari**. *University of Pittsburgh Department of Biomedical Informatics **All authors are currently with the University of Washington. This project is supported by a grant from the National Library of Medicine: "Addressing gaps in clinically useful evidence on drug-drug interactions" (1R01LM011838-01)
version info: The Drug Interaction Knowledge Base ontology. This version is reorganizes the evidence taxonomy for retrospective studies to more properly distinguish various observational studies. It also integrates type from EDDA (http://bioportal.bioontology.org/ontologies/EDDA)
version info: Version 1.6
imports: StudyDesigns.owl
imports: mp
imports: biopax-level3.owl

PhysicalEntity
type: ObjectProperty
type: FunctionalProperty
comment: Definition: A pool of molecules or molecular complexes. Comments: Each PhysicalEntity is defined by a sequence or structure based EntityReference AND a set of Features. For example, ser46 phosphorylated p53 is a physical entity in BioPAX defined by the p53 sequence and the phosphorylation feature. Features are any combination of cellular location, covalent and non-covalent bonds with other molecules and covalent modifications. For a specific molecule to be a member of the pool it has to satisfy all of the specified features. Unspecified features are treated as don't care. Features that should not be on the molecules should be explicitly stated with "not feature" property. A physical entity in BioPAX never represents a specific molecular instance. Physical Entity can be heterogenous and potentially overlap, i.e. a single molecule can be counted as a member of multiple pools. This makes BioPAX semantics different than regular chemical notation but is necessary for dealing with combinatorial complexity. Synonyms: part, interactor, object, species Examples: extracellular calcium, ser 64 phosphorylated p53
comment: The physical entity to be annotated with stoichiometry.
domain: Stoichiometry
type: Class
subclass of: Entity

Xref
type: ObjectProperty
comment: Definition: A reference from an instance of a class in this ontology to an object in an external resource. Rationale: Xrefs in the future can be removed in the future in favor of explicit miram links. Usage: For most cases one of the subclasses of xref should be used.
comment: Values of this property define external cross-references from this entity to entities in external databases.
domain: Class
  union of: BioSource
  union of: ControlledVocabulary
  union of: Entity
  union of: EntityReference
  union of: Evidence
  union of: Provenance
type: Class
subclass of: UtilityClass

absoluteRegion
type: ObjectProperty
type: FunctionalProperty
comment: Absolute location as defined by the referenced sequence database record. E.g. an operon has a absolute region on the DNA molecule referenced by the UnificationXref.
range: SequenceLocation
domain: Class
  union of: DnaRegionReference
  union of: RnaRegionReference

bindsTo
type: ObjectProperty
type: FunctionalProperty
type: InverseFunctionalProperty
type: SymmetricProperty
comment: A binding feature represents a "half" of the bond between two entities. This property points to another binding feature which represents the other half. The bond can be covalent or non-covalent.
range: BindingFeature
domain: BindingFeature

cellType
type: ObjectProperty
type: FunctionalProperty
comment: A cell type, e.g. 'HeLa'. This should reference a term in a controlled vocabulary of cell types. Best practice is to refer to OBO Cell Ontology. http://www.obofoundry.org/cgi-bin/detail.cgi?id=cell
domain: BioSource
range: CellVocabulary

cellularLocation
type: ObjectProperty
type: FunctionalProperty
comment: A cellular location, e.g. 'cytoplasm'. This should reference a term in the Gene Ontology Cellular Component ontology. The location referred to by this property should be as specific as is known. If an interaction is known to occur in multiple locations, separate interactions (and physicalEntities) must be created for each different location. If the location of a participant in a complex is unspecified, it may be assumed to be the same location as that of the complex. A molecule in two different cellular locations are considered two different physical entities.
range: CellularLocationVocabulary
domain: PhysicalEntity

cofactor
type: ObjectProperty
comment: Any cofactor(s) or coenzyme(s) required for catalysis of the conversion by the enzyme. COFACTOR is a sub-property of PARTICIPANTS.
domain: Catalysis
range: PhysicalEntity
sub property of: participant

componentStoichiometry
type: ObjectProperty
comment: The stoichiometry of components in a complex
domain: Complex
range: Stoichiometry

confidence
type: ObjectProperty
comment: Confidence in the containing instance. Usually a statistical measure.
domain: Evidence
range: Score

controlled
type: ObjectProperty
type: FunctionalProperty
comment: The entity that is controlled, e.g., in a biochemical reaction, the reaction is controlled by an enzyme. CONTROLLED is a sub-property of PARTICIPANTS.
domain: Control
sub property of: participant
range: Class
  union of: Interaction
  union of: Pathway

controller
type: ObjectProperty
comment: The controlling entity, e.g., in a biochemical reaction, an enzyme is the controlling entity of the reaction. CONTROLLER is a sub-property of PARTICIPANTS.
domain: Control
sub property of: participant
range: Class
  union of: Pathway
  union of: PhysicalEntity

dataSource
type: ObjectProperty
comment: A free text description of the source of this data, e.g. a database or person name. This property should be used to describe the source of the data. This is meant to be used by databases that export their data to the BioPAX format or by systems that are integrating data from multiple sources. The granularity of use (specifying the data source in many or few instances) is up to the user. It is intended that this property report the last data source, not all data sources that the data has passed through from creation.
domain: Entity
range: Provenance

deltaG
type: ObjectProperty
comment: For biochemical reactions, this property refers to the standard transformed Gibbs energy change for a reaction written in terms of biochemical reactants (sums of species), delta-G Since Delta-G can change based on multiple factors including ionic strength and temperature a reaction can have multiple DeltaG values.
domain: BiochemicalReaction
range: DeltaG

entityFeature
type: ObjectProperty
type: InverseFunctionalProperty
comment: Variable features that are observed for this entity - such as known PTM or methylation sites and non-covalent bonds.
range: EntityFeature
domain: EntityReference

entityReference
type: ObjectProperty
type: FunctionalProperty
comment: Reference entity for this physical entity.
range: EntityReference
domain: Class
  union of: Dna
  union of: DnaRegion
  union of: Protein
  union of: Rna
  union of: RnaRegion
  union of: SmallMolecule

entityReferenceType
type: ObjectProperty
type: FunctionalProperty
comment: A controlled vocabulary term that is used to describe the type of grouping such as homology or functional group.
domain: EntityReference
range: EntityReferenceTypeVocabulary

evidence
type: ObjectProperty
comment: Scientific evidence supporting the existence of the entity as described.
range: Evidence
domain: Class
  union of: Entity
  union of: EntityFeature
  union of: EntityReference
  union of: PathwayStep

evidenceCode
type: ObjectProperty
comment: A pointer to a term in an external controlled vocabulary, such as the GO, PSI-MI or BioCyc evidence codes, that describes the nature of the support, such as 'traceable author statement' or 'yeast two-hybrid'.
domain: Evidence
range: EvidenceCodeVocabulary

experimentalFeature
type: ObjectProperty
comment: A feature of the experimental form of the participant of the interaction, such as a protein tag. It is not expected to occur in vivo or be necessary for the interaction.
range: EntityFeature
domain: ExperimentalForm

experimentalForm
type: ObjectProperty
comment: The experimental forms associated with an evidence instance.
domain: Evidence
range: ExperimentalForm

experimentalFormDescription
type: ObjectProperty
comment: Descriptor of this experimental form from a controlled vocabulary.
domain: ExperimentalForm
range: ExperimentalFormVocabulary

experimentalFormEntity
type: ObjectProperty
comment: The gene or physical entity that this experimental form describes.
domain: ExperimentalForm
range: Class
  union of: Gene
  union of: PhysicalEntity

feature
type: ObjectProperty
comment: Sequence features of the owner physical entity.
range: EntityFeature
domain: PhysicalEntity

featureLocation
type: ObjectProperty
comment: Location of the feature on the sequence of the interactor. One feature may have more than one location, used e.g. for features which involve sequence positions close in the folded, three-dimensional state of a protein, but non-continuous along the sequence.
domain: EntityFeature
range: SequenceLocation

featureLocationType
type: ObjectProperty
comment: A controlled vocabulary term describing the type of the sequence location such as C-Terminal or SH2 Domain.
domain: EntityFeature
range: SequenceRegionVocabulary

interactionScore
type: ObjectProperty
comment: The score of an interaction e.g. a genetic interaction score.
domain: GeneticInteraction
range: Score

interactionType
type: ObjectProperty
comment: External controlled vocabulary annotating the interaction type, for example "phosphorylation". This is annotation useful for e.g. display on a web page or database searching, but may not be suitable for other computing tasks, like reasoning.
domain: Interaction
range: InteractionVocabulary

kEQ
type: ObjectProperty
comment: This quantity is dimensionless and is usually a single number. The measured equilibrium constant for a biochemical reaction, encoded by the slot KEQ, is actually the apparent equilibrium constant, K'. Concentrations in the equilibrium constant equation refer to the total concentrations of all forms of particular biochemical reactants. For example, in the equilibrium constant equation for the biochemical reaction in which ATP is hydrolyzed to ADP and inorganic phosphate: K' = [ADP][Pi]/[ATP], The concentration of ATP refers to the total concentration of all of the following species: [ATP] = [ATP4-] + [HATP3-] + [H2ATP2-] + [MgATP2-] + [MgHATP-] + [Mg2ATP]. The apparent equilibrium constant is formally dimensionless, and can be kept so by inclusion of as many of the terms (1 mol/dm3) in the numerator or denominator as necessary. It is a function of temperature (T), ionic strength (I), pH, and pMg (pMg = -log10[Mg2+]). Therefore, these quantities must be specified to be precise, and values for KEQ for biochemical reactions may be represented as 5-tuples of the form (K' T I pH pMg). This property may have multiple values, representing different measurements for K' obtained under the different experimental conditions listed in the 5-tuple. (This definition adapted from EcoCyc)
domain: BiochemicalReaction
range: KPrime

left
type: ObjectProperty
comment: The participants on the left side of the conversion interaction. Since conversion interactions may proceed in either the left-to-right or right-to-left direction, occupants of the LEFT property may be either reactants or products. LEFT is a sub-property of PARTICIPANTS.
domain: Conversion
range: PhysicalEntity
sub property of: participant

memberEntityReference
type: ObjectProperty
comment: An entity reference that qualifies for the definition of this group. For example a member of a PFAM protein family.
range: EntityReference
domain: EntityReference

memberFeature
type: ObjectProperty
type: TransitiveProperty
comment: An entity feature that belongs to this homology grouping. Example: a homologous phosphorylation site across a protein family.
domain: EntityFeature
range: EntityFeature

memberPhysicalEntity
type: ObjectProperty
type: TransitiveProperty
comment: This property stores the members of a generic physical entity. For representing homology generics a better way is to use generic entity references and generic features. However not all generic logic can be captured by this, such as complex generics or rare cases where feature cardinality is variable. Usages of this property should be limited to such cases.
range: PhysicalEntity
domain: PhysicalEntity

modificationType
type: ObjectProperty
type: FunctionalProperty
comment: Description and classification of the feature.
domain: ModificationFeature
range: SequenceModificationVocabulary

nextStep
type: ObjectProperty
comment: The next step(s) of the pathway. Contains zero or more pathwayStep instances. If there is no next step, this property is empty. Multiple pathwayStep instances indicate pathway branching.
domain: PathwayStep
range: PathwayStep

notFeature
type: ObjectProperty
comment: Sequence features where the owner physical entity has a feature. If not specified, other potential features are not known.
range: EntityFeature
domain: PhysicalEntity

organism
type: ObjectProperty
type: FunctionalProperty
comment: An organism, e.g. 'Homo sapiens'. This is the organism that the entity is found in. Pathways may not have an organism associated with them, for instance, reference pathways from KEGG. Sequence-based entities (DNA, protein, RNA) may contain an xref to a sequence database that contains organism information, in which case the information should be consistent with the value for ORGANISM.
range: BioSource
domain: Class
  union of: DnaReference
  union of: DnaRegionReference
  union of: Gene
  union of: Pathway
  union of: ProteinReference
  union of: RnaReference
  union of: RnaRegionReference

participant
type: ObjectProperty
comment: This property lists the entities that participate in this interaction. For example, in a biochemical reaction, the participants are the union of the reactants and the products of the reaction. This property has a number of sub-properties, such as LEFT and RIGHT used in the biochemicalInteraction class. Any participant listed in a sub-property will automatically be assumed to also be in PARTICIPANTS by a number of software systems, including Protege, so this property should not contain any instances if there are instances contained in a sub-property.
range: Entity
domain: Interaction

participantStoichiometry
type: ObjectProperty
comment: Stoichiometry of the left and right participants.
domain: Conversion
range: Stoichiometry

pathwayComponent
type: ObjectProperty
comment: The set of interactions and/or pathwaySteps in this pathway/network. Each instance of the pathwayStep class defines: 1) a set of interactions that together define a particular step in the pathway, for example a catalysis instance and the conversion that it catalyzes; 2) an order relationship to one or more other pathway steps (via the NEXT-STEP property). Note: This ordering is not necessarily temporal - the order described may simply represent connectivity between adjacent steps. Temporal ordering information should only be inferred from the direction of each interaction.
domain: Pathway
range: Class
  union of: Interaction
  union of: Pathway

pathwayOrder
type: ObjectProperty
comment: The ordering of components (interactions and pathways) in the context of this pathway. This is useful to specific circular or branched pathways or orderings when component biochemical reactions are normally reversible, but are directed in the context of this pathway.
domain: Pathway
range: PathwayStep

phenotype
type: ObjectProperty
type: FunctionalProperty
comment: The phenotype quality used to define this genetic interaction e.g. viability.
domain: GeneticInteraction
range: PhenotypeVocabulary

product
type: ObjectProperty
comment: The product of a template reaction.
domain: TemplateReaction
sub property of: participant
range: Class
  union of: Dna
  union of: Protein
  union of: Rna

right
type: ObjectProperty
comment: The participants on the right side of the conversion interaction. Since conversion interactions may proceed in either the left-to-right or right-to-left direction, occupants of the RIGHT property may be either reactants or products. RIGHT is a sub-property of PARTICIPANTS.
domain: Conversion
range: PhysicalEntity
sub property of: participant

sequenceIntervalBegin
type: ObjectProperty
type: FunctionalProperty
comment: The begin position of a sequence interval.
domain: SequenceInterval
range: SequenceSite

sequenceIntervalEnd
type: ObjectProperty
type: FunctionalProperty
comment: The end position of a sequence interval.
domain: SequenceInterval
range: SequenceSite

stepConversion
type: ObjectProperty
type: FunctionalProperty
comment: The central process that take place at this step of the biochemical pathway.
domain: BiochemicalPathwayStep
range: Conversion
sub property of: stepProcess

stepProcess
type: ObjectProperty
comment: An interaction or a pathway that are a part of this pathway step.
domain: PathwayStep
range: Class
  union of: Interaction
  union of: Pathway

structure
type: ObjectProperty
type: FunctionalProperty
comment: Defines the chemical structure and other information about this molecule, using an instance of class chemicalStructure.
range: ChemicalStructure
domain: SmallMoleculeReference

subRegion
type: ObjectProperty
comment: The sub region of a region or nucleic acid molecule. The sub region must be wholly part of the region, not outside of it.
domain: Class
  union of: DnaReference
  union of: DnaRegionReference
  union of: RnaReference
  union of: RnaRegionReference
range: Class
  union of: DnaRegionReference
  union of: RnaRegionReference

template
type: ObjectProperty
type: FunctionalProperty
comment: The template molecule that is used in this template reaction.
domain: TemplateReaction
sub property of: participant
range: Class
  union of: Dna
  union of: DnaRegion
  union of: Rna
  union of: RnaRegion

tissue
type: ObjectProperty
type: FunctionalProperty
comment: An external controlled vocabulary of tissue types.
domain: BioSource
range: TissueVocabulary

author
type: DatatypeProperty
comment: The authors of this publication, one per property value.
domain: PublicationXref
range: string

availability
type: DatatypeProperty
comment: Describes the availability of this data (e.g. a copyright statement).
domain: Entity
range: string

catalysisDirection
type: DatatypeProperty
type: FunctionalProperty
comment: This property represents the direction of this catalysis under all physiological conditions if there is one. Note that chemically a catalyst will increase the rate of the reaction in both directions. In biology, however, there are cases where the enzyme is expressed only when the controlled bidirectional conversion is on one side of the chemical equilibrium [todo : example]. If that is the case and the controller, under biological conditions, is always catalyzing the conversion in one direction then this fact can be captured using this property. If the enzyme is active for both directions, or the conversion is not bidirectional, this property should be left empty.
domain: Catalysis
range: Datatype
  one of: LEFT-TO-RIGHT
  one of: RIGHT-TO-LEFT

chemicalFormula
type: DatatypeProperty
type: FunctionalProperty
comment: The chemical formula of the small molecule. Note: chemical formula can also be stored in the STRUCTURE property (in CML). In case of disagreement between the value of this property and that in the CML file, the CML value takes precedence.
domain: SmallMoleculeReference
range: string

comment
type: DatatypeProperty
comment: Comment on the data in the container class. This property should be used instead of the OWL documentation elements (rdfs:comment) for instances because information in 'comment' is data to be exchanged, whereas the rdfs:comment field is used for metadata about the structure of the BioPAX ontology.
range: string
domain: Class
  union of: Entity
  union of: UtilityClass

controlType
type: DatatypeProperty
type: FunctionalProperty
comment: Defines the nature of the control relationship between the CONTROLLER and the CONTROLLED entities. The following terms are possible values: ACTIVATION: General activation. Compounds that activate the specified enzyme activity by an unknown mechanism. The mechanism is defined as unknown, because either the mechanism has yet to be elucidated in the experimental literature, or the paper(s) curated thus far do not define the mechanism, and a full literature search has yet to be performed. The following term can not be used in the catalysis class: INHIBITION: General inhibition. Compounds that inhibit the specified enzyme activity by an unknown mechanism. The mechanism is defined as unknown, because either the mechanism has yet to be elucidated in the experimental literature, or the paper(s) curated thus far do not define the mechanism, and a full literature search has yet to be performed. The following terms can only be used in the modulation class (these definitions from EcoCyc): INHIBITION-ALLOSTERIC Allosteric inhibitors decrease the specified enzyme activity by binding reversibly to the enzyme and inducing a conformational change that decreases the affinity of the enzyme to its substrates without affecting its VMAX. Allosteric inhibitors can be competitive or noncompetitive inhibitors, therefore, those inhibition categories can be used in conjunction with this category. INHIBITION-COMPETITIVE Competitive inhibitors are compounds that competitively inhibit the specified enzyme activity by binding reversibly to the enzyme and preventing the substrate from binding. Binding of the inhibitor and substrate are mutually exclusive because it is assumed that the inhibitor and substrate can both bind only to the free enzyme. A competitive inhibitor can either bind to the active site of the enzyme, directly excluding the substrate from binding there, or it can bind to another site on the enzyme, altering the conformation of the enzyme such that the substrate can not bind to th…
domain: Control
range: Datatype
  one of: ACTIVATION
  one of: ACTIVATION-ALLOSTERIC
  one of: ACTIVATION-NONALLOSTERIC
  one of: INHIBITION
  one of: INHIBITION-ALLOSTERIC
  one of: INHIBITION-COMPETITIVE
  one of: INHIBITION-IRREVERSIBLE
  one of: INHIBITION-NONCOMPETITIVE
  one of: INHIBITION-OTHER
  one of: INHIBITION-UNCOMPETITIVE

conversionDirection
type: DatatypeProperty
type: FunctionalProperty
comment: This property represents the direction of the reaction. If a reaction is fundamentally irreversible, then it will run in a single direction under all contexts. Otherwise it is reversible.
domain: Conversion
range: Datatype
  one of: LEFT-TO-RIGHT
  one of: REVERSIBLE
  one of: RIGHT-TO-LEFT

db
type: DatatypeProperty
type: FunctionalProperty
comment: The name of the external database to which this xref refers.
domain: Xref
range: string

dbVersion
type: DatatypeProperty
type: FunctionalProperty
comment: The version of the external database in which this xref was last known to be valid. Resources may have recommendations for referencing dataset versions. For instance, the Gene Ontology recommends listing the date the GO terms were downloaded.
domain: Xref
range: string

deltaGPrime0
type: DatatypeProperty
type: FunctionalProperty
comment: For biochemical reactions, this property refers to the standard transformed Gibbs energy change for a reaction written in terms of biochemical reactants (sums of species), delta-G'o. delta-G'o = -RT lnK' and delta-G'o = delta-H'o - T delta-S'o delta-G'o has units of kJ/mol. Like K', it is a function of temperature (T), ionic strength (I), pH, and pMg (pMg = -log10[Mg2+]). Therefore, these quantities must be specified, and values for DELTA-G for biochemical reactions are represented as 5-tuples of the form (delta-G'o T I pH pMg). (This definition from EcoCyc)
domain: DeltaG
range: float

deltaH
type: DatatypeProperty
comment: For biochemical reactions, this property refers to the standard transformed enthalpy change for a reaction written in terms of biochemical reactants (sums of species), delta-H'o. delta-G'o = delta-H'o - T delta-S'o Units: kJ/mole (This definition from EcoCyc)
domain: BiochemicalReaction
range: float

deltaS
type: DatatypeProperty
comment: For biochemical reactions, this property refers to the standard transformed entropy change for a reaction written in terms of biochemical reactants (sums of species), delta-S'o. delta-G'o = delta-H'o - T delta-S'o (This definition from EcoCyc)
domain: BiochemicalReaction
range: float

displayName
type: DatatypeProperty
type: FunctionalProperty
comment: An abbreviated name for this entity, preferably a name that is short enough to be used in a visualization application to label a graphical element that represents this entity. If no short name is available, an xref may be used for this purpose by the visualization application.
sub property of: name
range: string

eCNumber
type: DatatypeProperty
comment: The unique number assigned to a reaction by the Enzyme Commission of the International Union of Biochemistry and Molecular Biology. Note that not all biochemical reactions currently have EC numbers assigned to them.
domain: BiochemicalReaction
range: string

id
type: DatatypeProperty
type: FunctionalProperty
comment: The primary identifier in the external database of the object to which this xref refers.
domain: Xref
range: string

idVersion
type: DatatypeProperty
type: FunctionalProperty
comment: The version number of the identifier (ID). E.g. The RefSeq accession number NM_005228.3 should be split into NM_005228 as the ID and 3 as the ID-VERSION.
domain: Xref
range: string

intraMolecular
type: DatatypeProperty
type: FunctionalProperty
comment: This flag represents whether the binding feature is within the same molecule or not.
domain: BindingFeature
range: boolean

ionicStrength
type: DatatypeProperty
type: FunctionalProperty
comment: The ionic strength is defined as half of the total sum of the concentration (ci) of every ionic species (i) in the solution times the square of its charge (zi). For example, the ionic strength of a 0.1 M solution of CaCl2 is 0.5 x (0.1 x 22 + 0.2 x 12) = 0.3 M (Definition from http://www.lsbu.ac.uk/biology/enztech/ph.html)
range: float
domain: Class
  union of: DeltaG
  union of: KPrime

kPrime
type: DatatypeProperty
type: FunctionalProperty
comment: The apparent equilibrium constant K'. Concentrations in the equilibrium constant equation refer to the total concentrations of all forms of particular biochemical reactants. For example, in the equilibrium constant equation for the biochemical reaction in which ATP is hydrolyzed to ADP and inorganic phosphate: K' = [ADP][Pi]/[ATP], The concentration of ATP refers to the total concentration of all of the following species: [ATP] = [ATP4-] + [HATP3-] + [H2ATP2-] + [MgATP2-] + [MgHATP-] + [Mg2ATP]. The apparent equilibrium constant is formally dimensionless, and can be kept so by inclusion of as many of the terms (1 mol/dm3) in the numerator or denominator as necessary. It is a function of temperature (T), ionic strength (I), pH, and pMg (pMg = -log10[Mg2+]). (Definition from EcoCyc)
domain: KPrime
range: float

molecularWeight
type: DatatypeProperty
type: FunctionalProperty
comment: Defines the molecular weight of the molecule, in daltons.
domain: SmallMoleculeReference
range: float

name
type: DatatypeProperty
comment: One or more synonyms for the name of this individual. This should include the values of the standardName and displayName property so that it is easy to find all known names in one place.
range: string
domain: Class
  union of: BioSource
  union of: Entity
  union of: EntityReference
  union of: Provenance

pMg
type: DatatypeProperty
type: FunctionalProperty
comment: A measure of the concentration of magnesium (Mg) in solution. (pMg = -log10[Mg2+])
range: float
domain: Class
  union of: DeltaG
  union of: KPrime

patoData
type: DatatypeProperty
type: FunctionalProperty
comment: The phenotype data from PATO, formatted as PhenoXML (defined at http://www.fruitfly.org/~cjm/obd/formats.html)
domain: PhenotypeVocabulary
range: string

ph
type: DatatypeProperty
type: FunctionalProperty
comment: A measure of acidity and alkalinity of a solution that is a number on a scale on which a value of 7 represents neutrality and lower numbers indicate increasing acidity and higher numbers increasing alkalinity and on which each unit of change represents a tenfold change in acidity or alkalinity and that is the negative logarithm of the effective hydrogen-ion concentration or hydrogen-ion activity in gram equivalents per liter of the solution. (Definition from Merriam-Webster Dictionary)
range: float
domain: Class
  union of: DeltaG
  union of: KPrime

positionStatus
type: DatatypeProperty
type: FunctionalProperty
comment: The confidence status of the sequence position. This could be: EQUAL: The SEQUENCE-POSITION is known to be at the SEQUENCE-POSITION. GREATER-THAN: The site is greater than the SEQUENCE-POSITION. LESS-THAN: The site is less than the SEQUENCE-POSITION.
domain: SequenceSite
range: Datatype
  one of: EQUAL
  one of: GREATER-THAN
  one of: LESS-THAN

sequence
type: DatatypeProperty
type: FunctionalProperty
comment: Polymer sequence in uppercase letters. For DNA, usually A,C,G,T letters representing the nucleosides of adenine, cytosine, guanine and thymine, respectively; for RNA, usually A, C, U, G; for protein, usually the letters corresponding to the 20 letter IUPAC amino acid code.
range: string
domain: Class
  union of: DnaReference
  union of: DnaRegionReference
  union of: ProteinReference
  union of: RnaReference
  union of: RnaRegionReference

sequencePosition
type: DatatypeProperty
type: FunctionalProperty
comment: The integer listed gives the position. The first base or amino acid is position 1. In combination with the numeric value, the property 'POSITION-STATUS' allows to express fuzzy positions, e.g. 'less than 4'.
domain: SequenceSite
range: int

source
type: DatatypeProperty
comment: The source in which the reference was published, such as: a book title, or a journal title and volume and pages.
domain: PublicationXref
range: string

spontaneous
type: DatatypeProperty
type: FunctionalProperty
comment: Specifies whether a conversion occurs spontaneously or not. If the spontaneity is not known, the SPONTANEOUS property should be left empty.
domain: Conversion
range: boolean

standardName
type: DatatypeProperty
type: FunctionalProperty
comment: The preferred full name for this entity.
sub property of: name
range: string

stepDirection
type: DatatypeProperty
type: FunctionalProperty
comment: Direction of the conversion in this particular pathway context. This property can be used for annotating direction of enzymatic activity. Even if an enzyme catalyzes a reaction reversibly, the flow of matter through the pathway will force the equilibrium in a given direction for that particular pathway.
domain: BiochemicalPathwayStep
range: Datatype
  one of: LEFT-TO-RIGHT
  one of: REVERSIBLE
  one of: RIGHT-TO-LEFT

stoichiometricCoefficient
type: DatatypeProperty
type: FunctionalProperty
comment: Stoichiometric coefficient for one of the entities in an interaction or complex. This value can be any rational number. Generic values such as "n" or "n+1" should not be used - polymers are currently not covered.
domain: Stoichiometry
range: float

structureData
type: DatatypeProperty
type: FunctionalProperty
comment: This property holds a string of data defining chemical structure or other information, in either the CML or SMILES format, as specified in property Structure-Format. If, for example, the CML format is used, then the value of this property is a string containing the XML encoding of the CML data.
domain: ChemicalStructure
range: string

structureFormat
type: DatatypeProperty
type: FunctionalProperty
comment: This property specifies which format is used to define chemical structure data.
domain: ChemicalStructure
range: Datatype
  one of: CML
  one of: InChI
  one of: SMILES

temperature
type: DatatypeProperty
type: FunctionalProperty
comment: Temperature in Celsius
range: float
domain: Class
  union of: DeltaG
  union of: KPrime

templateDirection
type: DatatypeProperty
type: FunctionalProperty
comment: The direction of the template reaction on the template.
domain: TemplateReaction
range: Datatype
  one of: FORWARD
  one of: REVERSE

term
type: DatatypeProperty
comment: The external controlled vocabulary term.
domain: ControlledVocabulary
range: string

title
type: DatatypeProperty
type: FunctionalProperty
comment: The title of the publication.
domain: PublicationXref
range: string

url
type: DatatypeProperty
comment: The URL at which the publication can be found, if it is available through the Web.
domain: PublicationXref
range: string

value
type: DatatypeProperty
type: FunctionalProperty
comment: The value of the score.
domain: Score
range: string

year
type: DatatypeProperty
type: FunctionalProperty
comment: The year in which this publication was published.
domain: PublicationXref
range: int

Antibody
type: Class
subclass of: Protein
disjoint with: Cytochrome P450
comment: "An antibody is a type of protein made by B lymphocytes in response to a foreign substance (antigen). Each antibody only binds to a specific antigen, helping to destroy the antigen directly or by assisting white blood cells to destroy the antigen." NCI C16295 'Antibody'

Authoriative Organization
type: Class
disjoint with: Clinical Trial Participants
disjoint with: Drug
disjoint with: Drug Drug Interaction
disjoint with: Drug Interaction
disjoint with: Drug Manufacturer
disjoint with: EV PK DDI NR
disjoint with: Evidence Type
disjoint with: Journal Peer reviewed
disjoint with: Metabolism
disjoint with: Observation based DI Report Assessment tool
disjoint with: Pharmacodynamic Effect Consequences
disjoint with: Pharmacokinetic Effect Consequences
disjoint with: Pharmacokinetic Process
disjoint with: Public Reporting Database
disjoint with: Treatment Assignment
disjoint with: in vitro Protein Source
disjoint with: Entity
disjoint with: UtilityClass
comment: An agency or organized group of individual that whose opinions influence policy decisions

CYP1A2
type: Class
subclass of: Cytochrome P450
disjoint with: CYP2C19
disjoint with: CYP2C9
disjoint with: CYP2D6
disjoint with: CYP2E1
disjoint with: CYP3A4
disjoint with: CYP3A5
comment: cytochrome P450, family 1, subfamily A, polypeptide 2. A heme-thiolate monooxygenase. UniProtKB/Swiss-Prot entry P05177 summarizes the properties of this enzyme in humans. The HUGO Gene Nomenclature Committee (HGNC) database uses 'CYP1A2' as the symbol for the gene that codes this protein.

CYP2C19
type: Class
subclass of: Cytochrome P450
disjoint with: CYP2C9
disjoint with: CYP2D6
disjoint with: CYP2E1
disjoint with: CYP3A4
disjoint with: CYP3A5
comment: cytochrome P450, family 2, subfamily C, polypeptide 19. A heme-thiolate monooxygenase. UniProtKB/Swiss-Prot entry P33261 summarizes the properties of this enzyme in humans. The HUGO Gene Nomenclature Committee (HGNC) database uses 'CYP2C19' as the symbol for the gene that codes this protein.

CYP2C9
type: Class
subclass of: Cytochrome P450
disjoint with: CYP2D6
disjoint with: CYP2E1
disjoint with: CYP3A4
disjoint with: CYP3A5
comment: cytochrome P450, family 2, subfamily C, polypeptide 9. cytochrome P450, family 2, subfamily C, polypeptide 9. A heme-thiolate monooxygenase. UniProtKB/Swiss-Prot entry P11712 summarizes the properties of this enzyme in humans. The HUGO Gene Nomenclature Committee (HGNC) database uses 'CYP2C9' as the symbol for the gene that codes this protein.

CYP2D6
type: Class
subclass of: Cytochrome P450
disjoint with: CYP2E1
disjoint with: CYP3A4
disjoint with: CYP3A5
comment: cytochrome P450, family 2, subfamily D, polypeptide 6. A heme-thiolate monooxygenase. UniProtKB/Swiss-Prot entry P10635 summarizes the properties of this enzyme in humans. The HUGO Gene Nomenclature Committee (HGNC) database uses 'CYP2D6' as the symbol for the gene that codes this protein.

CYP2E1
type: Class
subclass of: Cytochrome P450
disjoint with: CYP3A4
disjoint with: CYP3A5
comment: cytochrome P450, family 2, subfamily E, polypeptide 1. A heme-thiolate monooxygenase. UniProtKB/Swiss-Prot entry P05181 summarizes the properties of this enzyme in humans. The HUGO Gene Nomenclature Committee (HGNC) database uses 'CYP2E1' as the symbol for the gene that codes this protein.

CYP3A4
type: Class
subclass of: Cytochrome P450
disjoint with: CYP3A5
comment: cytochrome P450, family 3, subfamily A; polypeptide 4. A heme-thiolate monooxygenase. UniProtKB/Swiss-Prot entry P08684 summarizes the properties of this enzyme in humans. The HUGO Gene Nomenclature Committee (HGNC) database uses 'CYP3A4' as the symbol for the gene that codes this protein.

CYP3A5
type: Class
subclass of: Cytochrome P450
comment: cytochrome P450, family 3, subfamily A; polypeptide 5. A heme-thiolate monooxygenase. UniProtKB/Swiss-Prot entry P20815 summarizes the properties of this enzyme in humans. The HUGO Gene Nomenclature Committee (HGNC) database uses 'CYP3A5' as the symbol for the gene that codes this protein.

Cellular Metabolism
type: Class
subclass of: Metabolism
comment: "The chemical reactions and pathways by which individual cells transform chemical substances." GO:0044237

Clinical Trial Participants
type: Class
disjoint with: Drug
disjoint with: Drug Drug Interaction
disjoint with: Drug Interaction
disjoint with: Drug Manufacturer
disjoint with: EV PK DDI NR
disjoint with: Evidence Type
disjoint with: Journal Peer reviewed
disjoint with: Metabolism
disjoint with: Observation based DI Report Assessment tool
disjoint with: Pharmacodynamic Effect Consequences
disjoint with: Pharmacokinetic Effect Consequences
disjoint with: Pharmacokinetic Process
disjoint with: Public Reporting Database
disjoint with: Treatment Assignment
disjoint with: in vitro Protein Source
disjoint with: Entity
disjoint with: UtilityClass
comment: Persons who have or are participating in a clinical trial

Cytochrome P450
type: Class
subclass of: Enzyme
subclass of: Protein
comment: "Cytochrome P450 isozymes, hemoprotein components of the mixed-function oxidase system involving electron and/or hydrogen transport through reversible valency change of the heme iron and metabolic biotransformation of substances, including foreign compounds to mutagens and carcinogens." Definition quote taken from NCI C26511 'Cytochrome_P450_Family_Gene', these are not synonomous types.

Decreased Drug AUC
type: Class
subclass of: Decreased Drug Level
comment: Decreased area under the plot of plasma concentration of a drug against time after drug administration NCI C54609 (2006)

Decreased Drug Level
type: Class
subclass of: Pharmacokinetic Effect Consequences
disjoint with: Increased Drug Level
comment: NCI C54356 (2006)

Drug
type: Class
subclass of: Thing
subclass of: Restriction
  on property: unifies with XRef
  some values from: Xref
disjoint with: Drug Drug Interaction
disjoint with: Drug Interaction
disjoint with: Drug Manufacturer
disjoint with: EV PK DDI NR
disjoint with: Evidence Type
disjoint with: Journal Peer reviewed
disjoint with: Metabolism
disjoint with: Observation based DI Report Assessment tool
disjoint with: Pharmacodynamic Effect Consequences
disjoint with: Pharmacokinetic Effect Consequences
disjoint with: Pharmacokinetic Process
disjoint with: Public Reporting Database
disjoint with: Treatment Assignment
disjoint with: in vitro Protein Source
disjoint with: UtilityClass
comment: "A category of organic or inorganic substances, elements, and isotopes used in research or for the prevention, diagnosis, and /or treatment of disease states. Includes biologically active substances that are either synthetically manufactured or endogenous substances extracted and processed to be reintroduced into an organism. Chemicals and drugs also include hazardous substances, and naturally occurring or synthetically produced substances required to maintain life. (NCI04)" Maps to: NCI code: C1908, Instances of this class are also sub-types of NDF-RT "active ingredients" code: C178

Drug Distribution
type: Class
subclass of: Pharmacokinetic Process
disjoint with: Drug Excretion
disjoint with: Drug Metabolism
comment: The directed movement of a drug, a substance used in the diagnosis, treatment or prevention of a disease, into, out of, within or between cells. GO:0015893 (GO 2006)

Drug Drug Interaction
type: Class
equivalent class: Class
  intersection of: Drug Interaction
  intersection of: Restriction
    on property: has object drug
    some values from: Drug
  intersection of: Restriction
    on property: has precipitant drug
    some values from: Drug
  intersection of: Restriction
    on property: has object drug
    all values from: Drug
  intersection of: Restriction
    on property: has precipitant drug
    all values from: Drug
disjoint with: Drug Manufacturer
disjoint with: Evidence Type
disjoint with: Journal Peer reviewed
disjoint with: Observation based DI Report Assessment tool
disjoint with: Pharmacodynamic Effect Consequences
disjoint with: Pharmacokinetic Effect Consequences
disjoint with: Pharmacokinetic Process
disjoint with: Public Reporting Database
disjoint with: Treatment Assignment
comment: "Alteration of the disposition and/or effect of a drug, owing to the presence of another drug" NCI 2007 ID:C54708

Drug Interaction
type: Class
subclass of: Thing
subclass of: Restriction
  on property: has consequence
  all values from: Class
    union of: Pharmacodynamic Effect Consequences
    union of: Pharmacokinetic Effect Consequences
subclass of: Restriction
  on property: has consequence
  some values from: Class
    union of: Pharmacodynamic Effect Consequences
    union of: Pharmacokinetic Effect Consequences
disjoint with: Drug Manufacturer
disjoint with: Evidence Type
disjoint with: Journal Peer reviewed
disjoint with: Metabolism
disjoint with: Observation based DI Report Assessment tool
disjoint with: Pharmacodynamic Effect Consequences
disjoint with: Pharmacokinetic Effect Consequences
disjoint with: Pharmacokinetic Process
disjoint with: Public Reporting Database
disjoint with: Treatment Assignment
disjoint with: in vitro Protein Source
disjoint with: Entity
disjoint with: UtilityClass
comment: "Alteration of the disposition and/or effect of a drug, owing to the presence of another factor such as a second drug, or food." NCI 2007 ID:C54708

Drug Label
type: Class
subclass of: Evidence Type
subclass of: Restriction
  on property: has sponser
  some values from: Drug Manufacturer
subclass of: Restriction
  on property: summarizes research on topic
  some values from: Drug
disjoint with: EV Case Report
disjoint with: EV Clinical Trial
disjoint with: EV EX Met Enz ID
disjoint with: EV EX Met Enz Inhibit
disjoint with: EV Observational
disjoint with: EV Review
disjoint with: EV Statement
comment: a document produced by a drug 's manufacturer to accompany a drug's container or wrapper whose statements might include the drug's indications, effects, dosages, routes, methods, frequency and duration of administration, warnings, hazards, contraindications, side effects, precautions, and other relevant information. Adapted from MeSH 2007 "Drug Labeling" ID: D004348

Drug Manufacturer
type: Class
subclass of: Thing
subclass of: Restriction
  on property: manufactures
  some values from: Drug
disjoint with: Evidence Type
disjoint with: Journal Peer reviewed
disjoint with: Metabolism
disjoint with: Observation based DI Report Assessment tool
disjoint with: Pharmacodynamic Effect Consequences
disjoint with: Pharmacokinetic Effect Consequences
disjoint with: Pharmacokinetic Process
disjoint with: Public Reporting Database
disjoint with: Treatment Assignment
disjoint with: in vitro Protein Source
disjoint with: Entity
disjoint with: UtilityClass
comment: A firm that legally manufactures drug products for sale on the wholesale or retail market

Drug Metabolism
type: Class
subclass of: Pharmacokinetic Process
subclass of: Xenobiotic Metabolism
comment: The chemical reactions and pathways involving a drug, a substance used in the diagnosis, treatment or prevention of a disease; as used here antibiotic substances (see antibiotic metabolism) are considered to be drugs, even if not used in medical or veterinary practice. GO:0017144 (2006)

EV CT DDI
type: Class
equivalent class: Class
  intersection of: EV Clinical Trial
  intersection of: Restriction
    on property: has focus of inquiry
    some values from: Drug Drug Interaction
  intersection of: Restriction
    on property: investigates drug
    some values from: Drug
  intersection of: Restriction
    on property: has focus of inquiry
    all values from: Drug Drug Interaction
  intersection of: Restriction
    on property: investigates drug
    all values from: Drug
disjoint with: EV CT Pharmacokinetic
comment: A study designed to quantify the pharmacokinetic and/or pharmacodynamic effects within study participants of a single drug (the object drug) in the presence of a purported precipitant.

EV CT PK DDI
type: Class
equivalent class: Class
  intersection of: EV CT DDI
  intersection of: Restriction
    on property: has focus of inquiry
    some values from: PK DDI
  intersection of: Restriction
    on property: has focus of inquiry
    all values from: PK DDI
disjoint with: EV CT Pharmacokinetic
comment: A study designed to quantify the pharmacokinetic effects within study participants of a single drug (the object drug) in the presence of a purported precipitant.

EV CT PK Genotype
type: Class
subclass of: EV CT Pharmacokinetic
comment: A drug pharmacokinetics study whose population consists of at least two groups known to posses distinct forms of some drug-metabolizing enzyme

EV CT PK Phenotype
type: Class
subclass of: EV CT Pharmacokinetic
comment: A drug pharmacokinetics study whose population consists of at least two groups known to posses distinct drug metabolizing phenotypes

EV CT Pharmacokinetic
type: Class
equivalent class: Class
  intersection of: EV Clinical Trial
  intersection of: Restriction
    on property: has focus of inquiry
    some values from: Pharmacokinetic Process
  intersection of: Restriction
    on property: investigates drug
    some values from: Drug
  intersection of: Restriction
    on property: has focus of inquiry
    all values from: Pharmacokinetic Process
  intersection of: Restriction
    on property: investigates drug
    all values from: Drug
comment: "A study of the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body." NCI code C49663

EV Case Report
type: Class
equivalent class: Restriction
  on property: has study design
  some values from: case design
subclass of: Evidence Type
disjoint with: EV Clinical Trial
disjoint with: EV EX Met Enz ID
disjoint with: EV EX Met Enz Inhibit
disjoint with: EV Observational
disjoint with: EV Review
disjoint with: EV Statement
comment: An observation-based report of some occurrence

EV Case Report ADE
type: Class
equivalent class: Class
  intersection of: EV Case Report
  intersection of: Restriction
    on property: describes
    some values from: Class
      union of: Pharmacodynamic Effect Consequences
      union of: Pharmacokinetic Effect Consequences
  intersection of: Restriction
    on property: describes
    all values from: Class
      union of: Pharmacodynamic Effect Consequences
      union of: Pharmacokinetic Effect Consequences
comment: An observation-based report of an adverse drug event

EV Case Report ADE Public Reported
type: Class
equivalent class: Class
  intersection of: EV Case Report ADE
  intersection of: Restriction
    on property: is recorded in
    some values from: Public Reporting Database
  intersection of: Restriction
    on property: is recorded in
    all values from: Public Reporting Database
comment: An adverse drug event report on file in a public adverse event reporting database such as the FDA's Adverse Event Reporting System

EV Case Report DI
type: Class
equivalent class: Class
  intersection of: EV Case Report ADE
  intersection of: Restriction
    on property: is published in
    some values from: Journal Peer reviewed
  intersection of: Restriction
    on property: is published in
    all values from: Journal Peer reviewed
comment: An published observation-based case-report of a drug interaction

EV Case Report DI Evaluated
type: Class
equivalent class: Class
  intersection of: EV Case Report DI
  intersection of: Restriction
    on property: has been evaluated by
    some values from: Observation based DI Report Assessment tool
  intersection of: Restriction
    on property: has been evaluated by
    all values from: Observation based DI Report Assessment tool
comment: An observation-based report of a drug interaction that has been evaluated by some assesssment tool

EV Clinical Trial
type: Class
equivalent class: Restriction
  on property: has study design
  some values from: clinical trial
subclass of: Evidence Type
subclass of: Restriction
  on property: has participants
  some values from: Clinical Trial Participants
subclass of: Restriction
  on property: has participants
  all values from: Clinical Trial Participants
disjoint with: EV EX Met Enz ID
disjoint with: EV EX Met Enz Inhibit
disjoint with: EV Observational
disjoint with: EV Review
disjoint with: EV Statement
comment: "a pre-planned clinical study of the safety, efficacy, or optimum dosage schedule of one or more diagnostic, therapeutic, or prophylactic drugs, devices, or techniques in humans selected according to predetermined criteria of eligibility and observed for predefined evidence of favorable and unfavorable effects." - Clinical Trial MeSH 2007

EV DrugClinicalReview
type: Class
subclass of: EV Drug Review
subclass of: Restriction
  on property: has sponser
  has value: US Food and Drug Administration
comment: An FDA-sponsered review of a drug's pre-market studies and adverse event reports.

EV Drug Review
type: Class
equivalent class: Class
  intersection of: EV Review
  intersection of: Restriction
    on property: is published in
    some values from: Journal Peer reviewed
  intersection of: Restriction
    on property: references
    some values from: Evidence Type
  intersection of: Restriction
    on property: summarizes research on topic
    some values from: Drug
  intersection of: Restriction
    on property: is published in
    all values from: Journal Peer reviewed
  intersection of: Restriction
    on property: references
    all values from: Evidence Type
  intersection of: Restriction
    on property: summarizes research on topic
    all values from: Drug
comment: A published analysis of research on the efficacy or safety of a drug, family of drugs, or drug therapy

EV EX Met Enz ID
type: Class
equivalent class: Class
  intersection of: Evidence Type
  intersection of: Restriction
    on property: has focus of inquiry
    some values from: Drug Metabolism
  intersection of: Restriction
    on property: has study design
    some values from: in vitro
  intersection of: Restriction
    on property: investigates drug
    some values from: Drug
  intersection of: Restriction
    on property: source of experimental protein
    some values from: in vitro Protein Source
  intersection of: Restriction
    on property: tests if drug is substrate of
    some values from: Enzyme
  intersection of: Restriction
    on property: has focus of inquiry
    all values from: Drug Metabolism
  intersection of: Restriction
    on property: investigates drug
    all values from: Drug
  intersection of: Restriction
    on property: source of experimental protein
    all values from: in vitro Protein Source
  intersection of: Restriction
    on property: tests if drug is substrate of
    all values from: Enzyme
disjoint with: EV EX Met Enz Inhibit
disjoint with: EV Observational
disjoint with: EV Statement
comment: A drug metabolism identification experiment -- an experiment conducted with biological tissues and/or chemical compounds in a laboratory designed to ``...identify the specific enzymes responsible for the metabolism of a drug'' (\cite{fda2006a}, p. 25)

EV EX Met Enz ID CYP450
type: Class
equivalent class: Class
  intersection of: EV EX Met Enz ID
  intersection of: Restriction
    on property: tests if drug is substrate of
    some values from: Cytochrome P450
  intersection of: Restriction
    on property: tests if drug is substrate of
    all values from: Cytochrome P450
comment: A metabolic enzyme identification experiment specifically designed to identify the Cytochrome P-450 enzymes involved in the metabolism of a drug

EV EX Met Enz ID CYP450 Hum Liver Microsome
type: Class
equivalent class: Class
  intersection of: EV EX Met Enz ID CYP450
  intersection of: Restriction
    on property: source of experimental protein
    has value: human liver microsomes
comment: A Cytochrome P-450 metabolic enzyme identification experiment using human liver microsomes that have been characterized for Cytochrome P-450 activity

EV EX Met Enz ID CYP450 Hum Liver Microsome Antibody
type: Class
equivalent class: Class
  intersection of: EV EX Met Enz ID CYP450 Hum Liver Microsome
  intersection of: Restriction
    on property: uses inhibitor of enzyme
    some values from: Antibody Inhibitor
  intersection of: Restriction
    on property: uses inhibitor of enzyme
    all values from: Antibody Inhibitor
comment: A Cytochrome P-450 metabolic enzyme identification experiment using human liver microsomes that have been characterized for Cytochrome P-450 activity and antibodies as specific inhibitors

EV EX Met Enz ID CYP450 Hum Liver Microsome Chem
type: Class
equivalent class: Class
  intersection of: EV EX Met Enz ID CYP450 Hum Liver Microsome
  intersection of: Restriction
    on property: uses inhibitor of enzyme
    some values from: Chemical Inhibitor
  intersection of: Restriction
    on property: uses inhibitor of enzyme
    all values from: Chemical Inhibitor
comment: A Cytochrome P-450 metabolic enzyme identification experiment using human liver microsomes that have been characterized for Cytochrome P-450 activity and chemical inhibitors

EV EX Met Enz ID CYP450 Hum Recom
type: Class
equivalent class: Class
  intersection of: EV EX Met Enz ID CYP450
  intersection of: Restriction
    on property: source of experimental protein
    has value: recombinant human cytochrome P450 isoenzymes
comment: A Cytochrome P450 metabolic enzyme identification experiment using recombinant human enzymes

EV EX Met Enz ID CYP450 Hum Recom Antibody
type: Class
equivalent class: Class
  intersection of: EV EX Met Enz ID CYP450 Hum Recom
  intersection of: Restriction
    on property: uses inhibitor of enzyme
    some values from: Antibody Inhibitor
  intersection of: Restriction
    on property: uses inhibitor of enzyme
    all values from: Antibody Inhibitor
comment: A Cytochrome P-450 metabolic enzyme identification experiment using recombinant human enzymes and antibodies as specific inhibitors

EV EX Met Enz ID CYP450 Hum Recom Chem
type: Class
equivalent class: Class
  intersection of: EV EX Met Enz ID CYP450 Hum Recom
  intersection of: Restriction
    on property: uses inhibitor of enzyme
    some values from: Chemical Inhibitor
  intersection of: Restriction
    on property: uses inhibitor of enzyme
    all values from: Chemical Inhibitor
comment: A Cytochrome P-450 metabolic enzyme identification experiment using recombinant human enzymes and chemical inhibitors

EV EX Met Enz Inhibit
type: Class
equivalent class: Class
  intersection of: Evidence Type
  intersection of: Restriction
    on property: has focus of inquiry
    some values from: Drug Metabolism
  intersection of: Restriction
    on property: has study design
    some values from: in vitro
  intersection of: Restriction
    on property: investigates drug
    some values from: Drug
  intersection of: Restriction
    on property: source of experimental protein
    some values from: in vitro Protein Source
  intersection of: Restriction
    on property: tests if drug inhibits
    some values from: Enzyme
  intersection of: Restriction
    on property: has focus of inquiry
    all values from: Drug Metabolism
  intersection of: Restriction
    on property: investigates drug
    all values from: Drug
  intersection of: Restriction
    on property: source of experimental protein
    all values from: in vitro Protein Source
  intersection of: Restriction
    on property: tests if drug inhibits
    all values from: Enzyme
disjoint with: EV Observational
disjoint with: EV Statement
comment: An experiment conducted with biological tissues and/or chemical compounds in a laboratory designed to determine whether or not a drug inhibits a specific drug-metabolizing enzyme

EV EX Met Enz Inhibit CYP450
type: Class
equivalent class: Class
  intersection of: EV EX Met Enz Inhibit
  intersection of: Restriction
    on property: tests if drug inhibits
    some values from: Cytochrome P450
  intersection of: Restriction
    on property: tests if drug inhibits
    all values from: Cytochrome P450
comment: A metabolic \textbf{inhibition} experiment specifically designed to determine whether or not a drug inhibits a specific CYP450 enzyme

EV EX Met Enz Inhibit CYP450 Human Liver Microsome
type: Class
equivalent class: Class
  intersection of: EV EX Met Enz Inhibit CYP450
  intersection of: Restriction
    on property: source of experimental protein
    has value: human liver microsomes
comment: A Cytochrome P-450 metabolic enzyme inhibition experiment using human liver microsomes that have been characterized for Cytochrome P-450 activity

EV EX Met Enz Inhibit CYP450 Human Recom
type: Class
equivalent class: Class
  intersection of: EV EX Met Enz Inhibit CYP450
  intersection of: Restriction
    on property: source of experimental protein
    has value: recombinant human cytochrome P450 isoenzymes
comment: A Cytochrome P-450 inhibition experiment using recombinant human enzymes

EV Non Tracable Statement
type: Class
subclass of: EV Statement
disjoint with: EV Traceable Statement
comment: A statement that does not explicitly refer to evidence items in justification of its assertion(s)

EV Non traceable Drug Label Statement
type: Class
equivalent class: Class
  intersection of: EV Non Tracable Statement
  intersection of: Restriction
    on property: is stated in
    some values from: Drug Label
  intersection of: Restriction
    on property: is stated in
    all values from: Drug Label
comment: An assertional statement in a drug label that does not provide any traceable citations for its evidence support

EV Observational
type: Class
equivalent class: Restriction
  on property: has study design
  some values from: observational design
subclass of: Evidence Type
disjoint with: EV Review
disjoint with: EV Statement
comment: A type of study in which individuals are observed or certain outcomes are measured. No attempt is made to affect the outcome (for example, no treatment is given). [NCIT_14.05d]

EV PK DDI NR
type: Class
equivalent class: Class
  intersection of: EV CT PK DDI
  intersection of: Restriction
    on property: has treatment assignment method
    some values from: Non randomized Tx Assignment
  intersection of: Restriction
    on property: has treatment assignment method
    all values from: Non randomized Tx Assignment
disjoint with: Pharmacokinetic Effect Consequences
disjoint with: Pharmacokinetic Process
disjoint with: Treatment Assignment
comment: A pharmacokinetic study where participants receive a drug either in the presence of a purported precipitant (experimental group) or not (control group) but participants are not randomly assigned to experiment and control groups

EV PK DDI Observational
type: Class
equivalent class: Class
  intersection of: EV Observational
  intersection of: Restriction
    on property: has focus of inquiry
    some values from: Pharmacokinetic Effect Consequences
  intersection of: Restriction
    on property: has focus of inquiry
    all values from: Pharmacokinetic Effect Consequences
comment: An observational study looking at the change in patient exposure of a single drug in the presence of a purported precipitant using an observational set of clinical records

EV PK DDI Par Grps
type: Class
equivalent class: Class
  intersection of: EV PK DDI NR
  intersection of: Restriction
    on property: has treatment assignment method
    has value: Parallel groups assignment
comment: A pharmacokinetic study involving two groups of non-randomized participants where both groups recieve the purported object drug while only one group receives the purported precipitant

EV PK DDI RCT
type: Class
equivalent class: Class
  intersection of: EV CT PK DDI
  intersection of: Restriction
    on property: has treatment assignment method
    some values from: Randomized Tx Assignment
  intersection of: Restriction
    on property: has treatment assignment method
    all values from: Randomized Tx Assignment
comment: A randomized, controlled, pharmacokinetic study where participants receive a drug wither in the presence of a purported precipitant (experimental group) or not (control group)

EV Population PK
type: Class
equivalent class: Class
  intersection of: EV Observational
  intersection of: Restriction
    on property: has focus of inquiry
    some values from: Pharmacokinetic Process
  intersection of: Restriction
    on property: has focus of inquiry
    all values from: Pharmacokinetic Process
comment: a ``...study of the sources and correlates of variability in drug concentrations among individuals who are the target patient population receiving clinically relevant doses of a drug in question.'' (\cite{fda1999b}, p.1)

EV Review
type: Class
equivalent class: Restriction
  on property: has study design
  some values from: review
subclass of: Evidence Type
disjoint with: EV Statement
comment: A published analysis of the evidence supportin and/or refuting some topic

EV Statement
type: Class
subclass of: QualifiedStatement
subclass of: Evidence Type
comment: "a message that is stated or declared; a communication (oral or written) setting forth particulars or facts etc" Wordnet v2.1

EV Traceable Drug Label Statement
type: Class
equivalent class: Class
  intersection of: EV Traceable Statement
  intersection of: Restriction
    on property: is stated in
    some values from: Drug Label
  intersection of: Restriction
    on property: is stated in
    all values from: Drug Label
comment: An assertion stated in a drug label that provides citations for its evidence support

EV Traceable Statement
type: Class
subclass of: ReferencedStatement
subclass of: EV Statement
comment: A statement that provides citation to evidence support for justification of its assertion(s)

Enzyme
type: Class
equivalent class: Class
  intersection of: PhysicalEntity
  intersection of: Restriction
    on property: lowers activation energy of
    some values from: MolecularInteraction
  intersection of: Restriction
    on property: lowers activation energy of
    all values from: MolecularInteraction
disjoint with: Complex
disjoint with: Dna
disjoint with: Rna
disjoint with: SmallMolecule
disjoint with: UtilityClass
comment: A physical entity "...that catalyzes a particular chemical reaction involving a specific substrate or small number of related substrates" \cite{lodish2004}

Evidence Type
type: Class
subclass of: Thing
disjoint with: Journal Peer reviewed
disjoint with: Metabolism
disjoint with: Observation based DI Report Assessment tool
disjoint with: Pharmacodynamic Effect Consequences
disjoint with: Pharmacokinetic Effect Consequences
disjoint with: Pharmacokinetic Process
disjoint with: Public Reporting Database
disjoint with: Treatment Assignment
disjoint with: in vitro Protein Source
disjoint with: Entity
comment: a kind of evidence where evidence is defined as an artifact that is "...the basis for belief or disbelief; knowledge on which to base belief" see "evidence" in Wordnet 2.1

Increased Drug AUC
type: Class
subclass of: Increased Drug Level
comment: Increased area under the plot of plasma concentration of a drug against time after drug administration. NCI C54605

Increased Drug Level
type: Class
subclass of: Pharmacokinetic Effect Consequences
comment: NCI C54355 (2006)

Induction
type: Class
subclass of: Modulation
disjoint with: Inhibition
comment: Definition: A control interaction in which a physical entity improves the ability of an enzyme to catalyze an interaction.

Inhibition
type: Class
subclass of: Modulation
comment: Definition: A control interaction in which a physical entity reduces the ability of an enzyme to catalyze an interaction.

Journal Peer reviewed
type: Class
disjoint with: Metabolism
disjoint with: Observation based DI Report Assessment tool
disjoint with: Pharmacodynamic Effect Consequences
disjoint with: Pharmacokinetic Effect Consequences
disjoint with: Pharmacokinetic Process
disjoint with: Public Reporting Database
disjoint with: Treatment Assignment
disjoint with: in vitro Protein Source
disjoint with: Entity
disjoint with: UtilityClass
comment: a periodical dedicated to a particular subject whose contents are reviewed by persons considered experts on the subject

Metabolism
type: Class
disjoint with: Observation based DI Report Assessment tool
disjoint with: Pharmacodynamic Effect Consequences
disjoint with: Pharmacokinetic Effect Consequences
disjoint with: Public Reporting Database
disjoint with: Treatment Assignment
disjoint with: in vitro Protein Source
disjoint with: UtilityClass
comment: "Processes that cause many of the chemical changes in living organisms, including anabolism and catabolism. Metabolic processes typically transform small molecules, but also include macromolecular processes such as DNA repair and replication, and protein synthesis and degradation." GO:0008152 'metabolism'

Microsomes
type: Class
subclass of: in vitro Protein Source
disjoint with: Recombinant Protein System
comment: "Any of the small, heterogeneous, artifactual, vesicular particles, 50-150 nm in diameter, that are formed when some eukaryotic cells are homogenized and that sediment on centrifugation at 100000 g." GO:0005792

Non randomized Tx Assignment
type: Class
subclass of: Treatment Assignment
disjoint with: Randomized Tx Assignment
comment: A non-randomized tratment assignment method

Observation based DI Report Assessment tool
type: Class
disjoint with: Pharmacodynamic Effect Consequences
disjoint with: Pharmacokinetic Effect Consequences
disjoint with: Pharmacokinetic Process
disjoint with: Public Reporting Database
disjoint with: Treatment Assignment
disjoint with: in vitro Protein Source
disjoint with: Entity
disjoint with: UtilityClass
comment: An assessment tool for grading the validity of an observation-based report's claims

PK DDI
type: Class
equivalent class: Class
  intersection of: Drug Drug Interaction
  intersection of: Restriction
    on property: effected by alteration of
    some values from: Pharmacokinetic Process
  intersection of: Restriction
    on property: effected by alteration of
    all values from: Pharmacokinetic Process
comment: A DDI that occurs via a pharmacokinetic mechanism

Pharmacodynamic Effect Consequences
type: Class
disjoint with: Pharmacokinetic Effect Consequences
disjoint with: Pharmacokinetic Process
disjoint with: Public Reporting Database
disjoint with: Treatment Assignment
disjoint with: in vitro Protein Source
disjoint with: UtilityClass
comment: The consequences resulted from pharmacodynamic interactions between the drug and another drug or food.

Pharmacokinetic Effect Consequences
type: Class
disjoint with: Pharmacokinetic Process
disjoint with: Public Reporting Database
disjoint with: Treatment Assignment
disjoint with: in vitro Protein Source
disjoint with: UtilityClass
comment: The consequences resulted from pharmacokinetic interactions between the drug and another drug or food. NCI C54354 (2006)

Pharmacokinetic Process
type: Class
disjoint with: Public Reporting Database
disjoint with: Treatment Assignment
disjoint with: in vitro Protein Source
disjoint with: UtilityClass
comment: A physiological process that moves molecular entities (e.g. drugs) within biological systems -- absorption, distribution, binding, elimination, biotransformation, and excretion

Public Reporting Database
type: Class
disjoint with: Treatment Assignment
disjoint with: in vitro Protein Source
disjoint with: Entity
disjoint with: UtilityClass
comment: A database that receives and stores reports of events of public health interest from various persons and makes these reports accessible to the general public

Randomized Tx Assignment
type: Class
subclass of: Treatment Assignment
comment: A randomized treatment assignment method

Recombinant Protein System
type: Class
subclass of: in vitro Protein Source
comment: A system of proteins "produced by genes or recombinant DNA that has been artificially engineered and inserted into a heterologous host. Recombinant proteins are used extensively by investigators of disease pathways to identify proteintargets for potential drug therapies." Adapted from NCI C17081 'Recombinant_Protein'

Treatment Assignment
type: Class
disjoint with: in vitro Protein Source
disjoint with: Entity
disjoint with: UtilityClass
comment: Method for assigning clinical trial participants to treatment and control groups

Xenobiotic Metabolism
type: Class
subclass of: Cellular Metabolism
comment: "The chemical reactions and pathways involving a xenobiotic compound, a compound foreign to living organisms. Used of chemical compounds, e.g. a xenobiotic chemical, such as a pesticide." GO:0006805

in vitro Protein Source
type: Class
disjoint with: Entity
disjoint with: UtilityClass
comment: A source of proteins that are used in biological experimentation

BindingFeature
type: Class
subclass of: EntityFeature
comment: Definition : An entity feature that represent the bound state of a physical entity. A pair of binding features represents a bond. Rationale: A physical entity in a molecular complex is considered as a new state of an entity as it is structurally and functionally different. Binding features provide facilities for describing these states. Similar to other features, a molecule can have bound and not-bound states. Usage: Typically, binding features are present in pairs, each describing the binding characteristic for one of the interacting physical entities. One exception is using a binding feature with no paired feature to describe any potential binding. For example, an unbound receptor can be described by using a "not-feature" property with an unpaired binding feature as its value. BindingSiteType and featureLocation allows annotating the binding location. IntraMolecular property should be set to "true" if the bond links two parts of the same molecule. A pair of binding features are still used where they are owned by the same physical entity. If the binding is due to the covalent interactions, for example in the case of lipoproteins, CovalentBindingFeature subclass should be used instead of this class.

BioSource
type: Class
subclass of: UtilityClass
comment: Definition: The biological source (organism, tissue or cell type) of an Entity. Usage: Some entities are considered source-neutral (e.g. small molecules), and the biological source of others can be deduced from their constituentss (e.g. complex, pathway). Instances: HeLa cells, Homo sapiens, and mouse liver tissue.

BiochemicalPathwayStep
type: Class
subclass of: PathwayStep
subclass of: Restriction
  on property: stepProcess
  all values from: Control
comment: Definition: Imposes ordering on a step in a biochemical pathway. Retionale: A biochemical reaction can be reversible by itself, but can be physiologically directed in the context of a pathway, for instance due to flux of reactants and products. Usage: Only one conversion interaction can be ordered at a time, but multiple catalysis or modulation instances can be part of one step.

BiochemicalReaction
type: Class
subclass of: Conversion
comment: Definition: An conversion in which molecules of one or more physicalEntity pools undergo covalent modifications and become a member of one or more other physicalEntity pools. The substrates of biochemical reactions are defined in terms of sums of species. This is convention in biochemistry, and, in principle, all of the EC reactions should be biochemical reactions. Examples: ATP + H2O = ADP + Pi Comment: In the example reaction above, ATP is considered to be an equilibrium mixture of several species, namely ATP4-, HATP3-, H2ATP2-, MgATP2-, MgHATP-, and Mg2ATP. Additional species may also need to be considered if other ions (e.g. Ca2+) that bind ATP are present. Similar considerations apply to ADP and to inorganic phosphate (Pi). When writing biochemical reactions, it is not necessary to attach charges to the biochemical reactants or to include ions such as H+ and Mg2+ in the equation. The reaction is written in the direction specified by the EC nomenclature system, if applicable, regardless of the physiological direction(s) in which the reaction proceeds. Polymerization reactions involving large polymers whose structure is not explicitly captured should generally be represented as unbalanced reactions in which the monomer is consumed but the polymer remains unchanged, e.g. glycogen + glucose = glycogen. A better coverage for polymerization is currently being developed.

Catalysis
type: Class
subclass of: Control
subclass of: Restriction
  on property: controlType
  has value: ACTIVATION
subclass of: Restriction
  on property: controlled
  all values from: Conversion
comment: Definition: A control interaction in which a physical entity (a catalyst) increases the rate of a conversion interaction by lowering its activation energy. Instances of this class describe a pairing between a catalyzing entity and a catalyzed conversion. Rationale: Catalysis, theoretically, is always bidirectional since it acts by lowering the activation energy. Physiologically, however, it can have a direction because of the concentration of the participants. For example the oxidative decarboxylation catalyzed by Isocitrate dehydrogenase always happens in one direction under physiological conditions since the produced carbon dioxide is constantly removed from the system. Usage: A separate catalysis instance should be created for each different conversion that a physicalEntity may catalyze and for each different physicalEntity that may catalyze a conversion. For example, a bifunctional enzyme that catalyzes two different biochemical reactions would be linked to each of those biochemical reactions by two separate instances of the catalysis class. Also, catalysis reactions from multiple different organisms could be linked to the same generic biochemical reaction (a biochemical reaction is generic if it only includes small molecules). Generally, the enzyme catalyzing a conversion is known and the use of this class is obvious. In the cases where a catalyzed reaction is known to occur but the enzyme is not known, a catalysis instance can be created without a controller specified. Synonyms: facilitation, acceleration. Examples: The catalysis of a biochemical reaction by an enzyme, the enabling of a transport interaction by a membrane pore complex, and the facilitation of a complex assembly by a scaffold protein. Hexokinase -> (The "Glucose + ATP -> Glucose-6-phosphate +ADP" reaction). A plasma membrane Na+/K+ ATPase is an active transporter (antiport pump) using the energy of ATP to pump Na+ out of the cell and K+ in. Na+ from cytoplasm to extracellular space would be des…

CellVocabulary
type: Class
subclass of: ControlledVocabulary
comment: Definition: A reference to the Cell Type Ontology (CL). Homepage at http://obofoundry.org/cgi-bin/detail.cgi?cell. Browse at http://www.ebi.ac.uk/ontology-lookup/browse.do?ontName=CL

CellularLocationVocabulary
type: Class
subclass of: ControlledVocabulary
comment: Definition: A reference to the Gene Ontology Cellular Component (GO CC) ontology. Homepage at http://www.geneontology.org. Browse at http://www.ebi.ac.uk/ontology-lookup/browse.do?ontName=GO

ChemicalStructure
type: Class
subclass of: UtilityClass
subclass of: Restriction
  on property: structureData
  cardinality: 1
subclass of: Restriction
  on property: structureFormat
  cardinality: 1
comment: Definition: The chemical structure of a small molecule. Usage: Structure information is stored in the property STRUCTURE-DATA, in one of three formats: the CML format (see URL www.xml-cml.org), the SMILES format (see URL www.daylight.com/dayhtml/smiles/) or the InChI format (http://www.iupac.org/inchi/). The STRUCTURE-FORMAT property specifies which format is used. Examples: The following SMILES string describes the structure of glucose-6-phosphate: 'C(OP(=O)(O)O)[CH]1([CH](O)[CH](O)[CH](O)[CH](O)O1)'.

Complex
type: Class
subclass of: PhysicalEntity
subclass of: Restriction
  on property: memberPhysicalEntity
  all values from: Complex
comment: Definition: A physical entity whose structure is comprised of other physical entities bound to each other covalently or non-covalently, at least one of which is a macromolecule (e.g. protein, DNA, or RNA). Comment: Complexes must be stable enough to function as a biological unit; in general, the temporary association of an enzyme with its substrate(s) should not be considered or represented as a complex. A complex is the physical product of an interaction (complexAssembly) and is not itself considered an interaction. The boundaries on the size of complexes described by this class are not defined here, although elements of the cell as large and dynamic as, e.g., a mitochondrion would typically not be described using this class (later versions of this ontology may include a cellularComponent class to represent these). The strength of binding cannot be described currently, but may be included in future versions of the ontology, depending on community need. Examples: Ribosome, RNA polymerase II. Other examples of this class include complexes of multiple protein monomers and complexes of proteins and small molecules.

ComplexAssembly
type: Class
subclass of: Conversion
comment: Definition: A conversion in which a set of physical entities, at least one being a macromolecule (e.g. protein, RNA, DNA), aggregate. This modification is captured via BindingFeature class. One of the participants of a complexAssembly must be an instance of the class Complex. Usage: This class is also used to represent complex disassembly. The assembly or disassembly of a complex is often a spontaneous process, in which case the direction of the complexAssembly (toward either assembly or disassembly) should be specified via the SPONTANEOUS property. Conversions in which participants obtain or lose CovalentBindingFeatures ( e.g. glycolysation of proteins) should be modeled with BiochemicalReaction. Synonyms: aggregation, complex formation Examples: Assembly of the TFB2 and TFB3 proteins into the TFIIH complex, and assembly of the ribosome through aggregation of its subunits.

Control
type: Class
subclass of: Interaction
disjoint with: GeneticInteraction
comment: Definition: An interaction in which one entity regulates, modifies, or otherwise influences a continuant entity, i.e. pathway or interaction. Usage: Conceptually, physical entities are involved in interactions (or events) and the events should be controlled or modified, not the physical entities themselves. For example, a kinase activating a protein is a frequent event in signaling pathways and is usually represented as an 'activation' arrow from the kinase to the substrate in signaling diagrams. This is an abstraction, called "Activity Flow" representation, that can be ambiguous without context. In BioPAX, this information should be captured as the kinase catalyzing (via an instance of the catalysis class) a Biochemical Reaction in which the substrate is phosphorylated. Subclasses of control define types specific to the biological process that is being controlled and should be used instead of the generic "control" class when applicable. A control can potentially have multiple controllers. This acts as a logical AND, i.e. both controllers are needed to regulate the controlled event. Alternatively multiple controllers can control the same event and this acts as a logical OR, i.e. any one of them is sufficient to regulate the controlled event. Using this structure it is possible to describe arbitrary control logic using BioPAX. Rationale: Control can be temporally non-atomic, for example a pathway can control another pathway in BioPAX. Synonyms: regulation, mediation Examples: A small molecule that inhibits a pathway by an unknown mechanism.

Conversion
type: Class
subclass of: Interaction
subclass of: Restriction
  on property: participant
  all values from: PhysicalEntity
disjoint with: GeneticInteraction
comment: Definition: An interaction in which molecules of one or more physicalEntity pools are physically transformed and become a member of one or more other physicalEntity pools. Comments: Conversions in BioPAX are stoichiometric and closed world, i.e. i is assumed that all of the participants are listed. Both properties are due to the law of mass conservation. Usage: Subclasses of conversion represent different types of transformation reflected by different physicalEntity properties. BiochemicalReaction will change the ModificationFeatures on the PhysicalEntity , Transport will change the CellularLocation and ComplexAssembly will change the BindingFeature. Generic Conversion class should only be used when the modification does not fit into one of these classes. Example: Opening of a voltage gated channel.

CovalentBindingFeature
type: Class
subclass of: BindingFeature
subclass of: ModificationFeature
comment: Definition : An entity feature that represent the covalently bound state of a physical entity. Rationale: Most frequent covalent modifications to proteins and DNA, such as phosphorylation and metylation are covered by the ModificationFeature class. In these cases, the added groups are simple and stateless therefore they can be captured by a controlled vocabulary. In other cases, such as ThiS-Thilacyl-disulfide, the covalently linked molecules are best represented as a molecular complex. CovalentBindingFeature should be used to model such covalently linked complexes. Usage: Using this construct, it is possible to represent small molecules as a covalent complex of two other small molecules. The demarcation of small molecules is a general problem and is delegated to small molecule databases.The best practice is not to model using covalent complexes unless at least one of the participants is a protein, DNA or RNA. Examples: disulfide bond UhpC + glc-6P -> Uhpc-glc-6p acetyl-ACP -> decenoyl-ACP charged tRNA

Degradation
type: Class
subclass of: Conversion
subclass of: Restriction
  on property: conversionDirection
  has value: LEFT-TO-RIGHT
comment: Definition: A conversion in which a pool of macromolecules are degraded into their ubiquitous elementary subunits. Usage: This conversion always has a direction of left-to-right and is irreversible. Degraded molecules are always represented on the left, degradation products on the right. Comments: Degradation is a complex abstraction over multiple reactions. Although it obeys law of mass conservation and stoichiometric, the products are rarely specified since they are ubiquitous. Example: Degradation of a protein to amino acids.

DeltaG
type: Class
subclass of: UtilityClass
subclass of: Restriction
  on property: deltaGPrime0
  cardinality: 1
comment: Definition: Standard transformed Gibbs energy change for a reaction written in terms of biochemical reactants. Usage: Delta-G is represented as a 5-tuple of delta-G'0, temperature, ionic strength , pH, and pMg . A conversion in BioPAX may have multiple Delta-G values, representing different measurements for delta-G'0 obtained under the different experimental conditions.

Dna
type: Class
subclass of: PhysicalEntity
subclass of: Restriction
  on property: memberPhysicalEntity
  all values from: Dna
subclass of: Restriction
  on property: entityReference
  all values from: DnaReference
disjoint with: Protein
disjoint with: Rna
comment: Definition: A physical entity consisting of a sequence of deoxyribonucleotide monophosphates; a deoxyribonucleic acid. Usage: DNA should be used for pools of individual DNA molecules. For describing subregions on those molecules use DNARegion. Examples: a chromosome, a plasmid. A specific example is chromosome 7 of Homo sapiens.

DnaReference
type: Class
subclass of: EntityReference
subclass of: Restriction
  on property: subRegion
  all values from: DnaRegionReference
subclass of: Restriction
  on property: memberEntityReference
  all values from: DnaReference
comment: Definition: A DNA reference is a grouping of several DNA entities that are common in sequence. Members can differ in celular location, sequence features, SNPs, mutations and bound partners. Comments : Note that this is not a reference gene. Genes are non-physical,stateless continuants. Their physical manifestations can span multiple DNA molecules, sometimes even across chromosomes due to regulatory regions. Similarly a gene is not necessarily made up of deoxyribonucleic acid and can be present in multiple copies ( which are different DNA regions).

DnaRegion
type: Class
subclass of: PhysicalEntity
subclass of: Restriction
  on property: memberPhysicalEntity
  all values from: DnaRegion
subclass of: Restriction
  on property: entityReference
  all values from: DnaRegionReference
comment: Definition: A region on a DNA molecule. Usage: DNARegion is not a pool of independent molecules but a subregion on these molecules. As such, every DNARegion has a defining DNA molecule. Examples: Proteing encoding region, promoter

DnaRegionReference
type: Class
subclass of: EntityReference
subclass of: Restriction
  on property: subRegion
  all values from: DnaRegionReference
comment: Definition: A DNA reference is a grouping of several DNA entities that are common in sequence and genomic position. Members can differ in celular location, sequence features, SNPs, mutations and bound partners.

Entity
type: Class
comment: Definition: A discrete biological unit used when describing pathways. Rationale: Entity is the most abstract class for representing interacting elements in a pathway. It includes both occurents (interactions and pathways) and continuants (physical entities and genes). Loosely speaking, BioPAX Entity is an atomic scientific statement with an associated source, evidence and references. Synonyms: element, thing, object, bioentity, statement.

EntityFeature
type: Class
subclass of: UtilityClass
comment: Description: A characteristic of a physical entity that can change while the entity still retains its biological identity. Rationale: Two phosphorylated forms of a protein are strictly speaking different chemical molecules. It is, however, standard in biology to treat them as different states of the same entity, where the entity is loosely defined based on sequence. Entity Feature class and its subclassses captures these variable characteristics. A Physical Entity in BioPAX represents a pool of molecules rather than an individual molecule. This is a notion imported from chemistry( See PhysicalEntity). Pools are defined by a set of Entity Features in the sense that a single molecule must have all of the features in the set in order to be considered a member of the pool. Since it is impossible to list and experimentally test all potential features for an entity, features that are not listed in the selection criteria is neglected Pools can also be defined by the converse by specifying features that are known to NOT exist in a specific context. As DNA, RNA and Proteins can be hierarchicaly organized into families based on sequence homology so can entity features. The memberFeature property allows capturing such hierarchical classifications among entity features. Usage: Subclasses of entity feature describe most common biological instances and sholud be preferred whenever possible. One common usecase for instatiating entity feature is, for describing active/inactive states of proteins where more specific feature information is not available. Instances: Open/close conformational state of channel proteins, "active"/"inactive" states, excited states of photoreactive groups.

EntityReference
type: Class
subclass of: UtilityClass
comment: Definition: An entity reference is a grouping of several physical entities across different contexts and molecular states, that share common physical properties and often named and treated as a single entity with multiple states by biologists. Rationale: Many protein, small molecule and gene databases share this point of view, and such a grouping is an important prerequisite for interoperability with those databases. Biologists would often group different pools of molecules in different contexts under the same name. For example cytoplasmic and extracellular calcium have different effects on the cell's behavior, but they are still called calcium. For DNA, RNA and Proteins the grouping is defined based on a wildtype sequence, for small molecules it is defined by the chemical structure. Usage: Entity references store the information common to a set of molecules in various states described in the BioPAX document, including database cross-references. For instance, the P53 protein can be phosphorylated in multiple different ways. Each separate P53 protein (pool) in a phosphorylation state would be represented as a different protein (child of physicalEntity) and all things common to all P53 proteins, including all possible phosphorylation sites, the sequence common to all of them and common references to protein databases containing more information about P53 would be stored in a Entity Reference. Comments: This grouping has three semantic implications: 1. Members of different pools share many physical and biochemical properties. This includes their chemical structure, sequence, organism and set of molecules they react with. They will also share a lot of secondary information such as their names, functional groupings, annotation terms and database identifiers. 2. A small number of transitions seperates these pools. In other words it is relatively easy and frequent for a molecule to transform from one physical entity to another that belong to the same reference entity. For …

EntityReferenceTypeVocabulary
type: Class
subclass of: ControlledVocabulary
comment: Definiiton: A reference to a term from a reference entity group ontology. There is no "best-practice" vocabulary for this one.

Evidence
type: Class
subclass of: UtilityClass
subclass of: Class
  union of: Restriction
    on property: confidence
    min cardinality: 1
  union of: Restriction
    on property: evidenceCode
    min cardinality: 1
  union of: Restriction
    on property: experimentalForm
    min cardinality: 1
comment: Definition: The support for a particular assertion, such as the existence of an interaction or pathway. Usage: At least one of CONFIDENCE, EVIDENCE-CODE, or EXPERIMENTAL-FORM must be instantiated when creating an evidence instance. XREF may reference a publication describing the experimental evidence using a publicationXref or may store a description of the experiment in an experimental description database using a unificationXref (if the referenced experiment is the same) or relationshipXref (if it is not identical, but similar in some way e.g. similar in protocol). Evidence is meant to provide more information than just an xref to the source paper. Examples: A description of a molecular binding assay that was used to detect a protein-protein interaction.

EvidenceCodeVocabulary
type: Class
subclass of: ControlledVocabulary
comment: Definition: A reference to the PSI Molecular Interaction ontology (MI) experimental method types, including "interaction detection method", "participant identification method", "feature detection method". Homepage at http://www.psidev.info/. Browse at http://www.ebi.ac.uk/ontology-lookup/browse.do?ontName=MI Terms from the Pathway Tools Evidence Ontology may also be used. Homepage http://brg.ai.sri.com/evidence-ontology/

ExperimentalForm
type: Class
subclass of: UtilityClass
subclass of: Restriction
  on property: experimentalFormDescription
  min cardinality: 1
comment: Definition: The form of a physical entity in a particular experiment, as it may be modified for purposes of experimental design. Examples: A His-tagged protein in a binding assay. A protein can be tagged by multiple tags, so can have more than 1 experimental form type terms

ExperimentalFormVocabulary
type: Class
subclass of: ControlledVocabulary
comment: Definition: A reference to the PSI Molecular Interaction ontology (MI) participant identification method (e.g. mass spectrometry), experimental role (e.g. bait, prey), experimental preparation (e.g. expression level) type. Homepage at http://www.psidev.info/. Browse http://www.ebi.ac.uk/ontology-lookup/browse.do?ontName=MI&termId=MI%3A0002&termName=participant%20identification%20method http://www.ebi.ac.uk/ontology-lookup/browse.do?ontName=MI&termId=MI%3A0495&termName=experimental%20role http://www.ebi.ac.uk/ontology-lookup/browse.do?ontName=MI&termId=MI%3A0346&termName=experimental%20preparation

FragmentFeature
type: Class
subclass of: EntityFeature
comment: Definition: An entity feature that represents the resulting physical entity subsequent to a cleavage or degradation event. Usage: Fragment Feature can be used to cover multiple types of modfications to the sequence of the physical entity: 1. A protein with a single cleavage site that converts the protein into two fragments (e.g. pro-insulin converted to insulin and C-peptide). TODO: CV term for sequence fragment? PSI-MI CV term for cleavage site? 2. A protein with two cleavage sites that removes an internal sequence e.g. an intein i.e. ABC -> A 3. Cleavage of a circular sequence e.g. a plasmid. In the case of removal ( e.g. intron) the fragment that is *removed* is specified in the feature location property. In the case of a "cut" (e.g. restriction enzyme cut site) the location of the cut is specified instead. Examples: Insulin Hormone

Gene
type: Class
subclass of: Entity
subclass of: Restriction
  on property: organism
  max cardinality: 1
disjoint with: Interaction
disjoint with: Pathway
disjoint with: PhysicalEntity
comment: Definition: A continuant that encodes information that can be inherited through replication. Rationale: Gene is and abstract continuant that can be best described as a "schema". Gene in BioPAX is a generelization over eukaryotic and prokaryotic genes and used only for genetic interactions. Gene is often confused with DNA and RNA fragments that are physical encoding of the gene. Gene expression regulation makes use of DNA and RNA physical entities. Usage: Gene should only be used for describing GeneticInteractions.

GeneticInteraction
type: Class
subclass of: Interaction
subclass of: Restriction
  on property: phenotype
  cardinality: 1
subclass of: Restriction
  on property: participant
  all values from: Gene
subclass of: Restriction
  on property: participant
  min cardinality: 2
subclass of: Restriction
  on property: interactionType
  max cardinality: 1
disjoint with: MolecularInteraction
disjoint with: TemplateReaction
comment: Definition : Genetic interactions between genes occur when two genetic perturbations (e.g. mutations) have a combined phenotypic effect not caused by either perturbation alone. A gene participant in a genetic interaction represents the gene that is perturbed. Genetic interactions are not physical interactios but logical (AND) relationships. Their physical manifestations can be complex and span an arbitarily long duration. Rationale: Currently, BioPAX provides a simple definition that can capture most genetic interactions described in the literature. In the future, if required, the definition can be extended to capture other logical relationships and different, participant specific phenotypes. Example: A synthetic lethal interaction occurs when cell growth is possible without either gene A OR B, but not without both gene A AND B. If you knock out A and B together, the cell will die.

Interaction
type: Class
subclass of: Entity
disjoint with: Pathway
disjoint with: PhysicalEntity
comment: Definition: A biological relationship between two or more entities. Rationale: BioPAX interactions are atomic from modeling perspective, i.e. it is not possible to define sub-interactions. For representing non-atomic continuants with explicit subevents, pathway class should be used. Interactions does not have to be temporally atomic though, for example genetic interactions cover a large span of time. Usage: Interaction is a highly abstract class and in almost all cases it is more appropriate to use subclasses of interaction. It is partially possible to define generic reactions by using generic participants. A more comprehensive method is planned for BioPAX L4 for covering all generic cases like oxidization of a generic alcohol. Synonyms: Process, relationship, event. Examples: protein-protein interaction, biochemical reaction, enzyme catalysis

InteractionVocabulary
type: Class
subclass of: ControlledVocabulary
comment: Definition: A reference to the PSI Molecular Interaction ontology (MI) interaction type. Homepage at http://www.psidev.info/. Browse at http://www.ebi.ac.uk/ontology-lookup/browse.do?ontName=MI&termId=MI%3A0190&termName=interaction%20type

KPrime
type: Class
subclass of: UtilityClass
subclass of: Restriction
  on property: kPrime
  cardinality: 1
comment: Definition: The apparent equilibrium constant, K', and associated values. Usage: Concentrations in the equilibrium constant equation refer to the total concentrations of all forms of particular biochemical reactants. For example, in the equilibrium constant equation for the biochemical reaction in which ATP is hydrolyzed to ADP and inorganic phosphate: K' = [ADP][Pi]/[ATP], The concentration of ATP refers to the total concentration of all of the following species: [ATP] = [ATP4-] + [HATP3-] + [H2ATP2-] + [MgATP2-] + [MgHATP-] + [Mg2ATP]. The apparent equilibrium constant is formally dimensionless, and can be kept so by inclusion of as many of the terms (1 mol/dm3) in the numerator or denominator as necessary. It is a function of temperature (T), ionic strength (I), pH, and pMg (pMg = -log10[Mg2+]). Therefore, these quantities must be specified to be precise, and values for KEQ for biochemical reactions may be represented as 5-tuples of the form (K' T I pH pMg). This property may have multiple values, representing different measurements for K' obtained under the different experimental conditions listed in the 5-tuple. (This definition adapted from EcoCyc) See http://www.chem.qmul.ac.uk/iubmb/thermod/ for a thermodynamics tutorial.

ModificationFeature
type: Class
subclass of: EntityFeature
comment: Definition: An entity feature that represents the covalently modified state of a dna, rna or a protein. Rationale: In Biology, identity of DNA, RNA and Protein entities are defined around a wildtype sequence. Covalent modifications to this basal sequence are represented using modificaton features. Since small molecules are identified based on their chemical structure, not sequence, a covalent modification to a small molecule would result in a different molecule. Usage: The added groups should be simple and stateless, such as phosphate or methyl groups and are captured by the modificationType controlled vocabulary. In other cases, such as covalently linked proteins, use CovalentBindingFeature instead. Instances: A phosphorylation on a protein, a methylation on a DNA.

Modulation
type: Class
subclass of: Control
subclass of: Restriction
  on property: controlled
  all values from: Catalysis
subclass of: Restriction
  on property: controller
  all values from: PhysicalEntity
comment: Definition: A control interaction in which a physical entity modulates a catalysis interaction. Biologically, most modulation interactions describe an interaction in which a small molecule alters the ability of an enzyme to catalyze a specific reaction. Instances of this class describe a pairing between a modulating entity and a catalysis interaction. Comment: A separate modulation instance should be created for each different catalysis instance that a physical entity may modulate and for each different physical entity that may modulate a catalysis instance. A typical modulation instance has a small molecule as the controller entity and a catalysis instance as the controlled entity. Examples: Allosteric activation and competitive inhibition of an enzyme's ability to catalyze a specific reaction.
comment: Definition: A control interaction in which a physical entity modulates a catalysis interaction. Rationale: Biologically, most modulation interactions describe an interaction in which a small molecule alters the ability of an enzyme to catalyze a specific reaction. Instances of this class describe a pairing between a modulating entity and a catalysis interaction. Usage: A separate modulation instance should be created for each different catalysis instance that a physical entity may modulate and for each different physical entity that may modulate a catalysis instance. A typical modulation instance has a small molecule as the controller entity and a catalysis instance as the controlled entity. Examples: Allosteric activation and competitive inhibition of an enzyme's ability to catalyze a specific reaction.

MolecularInteraction
type: Class
subclass of: Interaction
subclass of: Restriction
  on property: participant
  all values from: PhysicalEntity
comment: Definition: An interaction in which participants bind physically to each other,directly or indirectly through intermediary molecules. Rationale: There is a large body of interaction data, mostly produced by high throughput systems, that does not satisfy the level of detail required to model them with ComplexAssembly class. Specifically, what is lacking is the stoichiometric information and completeness ( closed-world) of participants required to model them as chemical processes. Nevertheless interaction data is extremely useful and can be captured in BioPAX using this class. Usage: This class should be used by default for representing molecular interactions, such as those defined by PSI-MI level 2.5. The participants in a molecular interaction should be listed in the PARTICIPANTS slot. Note that this is one of the few cases in which the PARTICPANT slot should be directly populated with instances (see comments on the PARTICPANTS property in the interaction class description). If all participants are known with exact stoichiometry, ComplexAssembly class should be used instead. Example: Two proteins observed to interact in a yeast-two-hybrid experiment where there is not enough experimental evidence to suggest that the proteins are forming a complex by themselves without any indirect involvement of other proteins. This is the case for most large-scale yeast two-hybrid screens.

Pathway
type: Class
subclass of: Entity
disjoint with: PhysicalEntity
comment: Definition: A set or series of interactions, often forming a network, which biologists have found useful to group together for organizational, historic, biophysical or other reasons. Usage: Pathways can be used for demarcating any subnetwork of a BioPAX model. It is also possible to define a pathway without specifying the interactions within the pathway. In this case, the pathway instance could consist simply of a name and could be treated as a 'black box'. Pathways can overlap, i.e. a single interaction might belong to multiple pathways. Pathways can also contain sub-pathways. Synonyms: network, module, cascade, Examples: glycolysis, valine biosynthesis, EGFR signaling

PathwayStep
type: Class
subclass of: UtilityClass
comment: Definition: A step in an ordered pathway. Rationale: Some pathways can have a temporal order. For example if the pathway boundaries is based on a perturbation phenotype link the pathway might start with the perturbing agent and end at gene expression leading to the observed changes. Pathway steps can represent directed compound graphs. Usage: Multiple interactions may occur in a pathway step, each should be listed in the STEP-INTERACTION property. Order relationships between pathway steps may be established with the NEXT-STEP slot. If the reaction contained in the step is a reversible biochemical reaction but physiologically has a direction in the context of this pathway, use Biochemical Pathway Step instead. Example: A metabolic pathway may contain a pathway step composed of one biochemical reaction (BR1) and one catalysis (CAT1) instance, where CAT1 describes the catalysis of BR1. The M phase of the cell cycle, defined as a pathway, precedes the G1 phase, also defined as a pathway.

PhenotypeVocabulary
type: Class
subclass of: ControlledVocabulary
comment: Definition: The phenotype measured in the experiment e.g. growth rate or viability of a cell. This is only the type, not the value e.g. for a synthetic lethal interaction, the phenotype is viability, specified by ID: PATO:0000169, "viability", not the value (specified by ID: PATO:0000718, "lethal (sensu genetics)". A single term in a phenotype controlled vocabulary can be referenced using the xref, or the PhenoXML describing the PATO EQ model phenotype description can be stored as a string in PATO-DATA.

Protein
type: Class
subclass of: PhysicalEntity
subclass of: Restriction
  on property: entityReference
  all values from: ProteinReference
subclass of: Restriction
  on property: memberPhysicalEntity
  all values from: Protein
disjoint with: Rna
comment: Definition: A physical entity consisting of a sequence of amino acids; a protein monomer; a single polypeptide chain. Examples: The epidermal growth factor receptor (EGFR) protein.

ProteinReference
type: Class
subclass of: EntityReference
subclass of: Restriction
  on property: memberEntityReference
  all values from: ProteinReference
comment: A protein reference is a grouping of several protein entities that are encoded by the same gene. Members can differ in celular location, sequence features and bound partners. Currently conformational states (such as open and closed) are not covered.

Provenance
type: Class
subclass of: UtilityClass
subclass of: Restriction
  on property: Xref
  all values from: Class
    union of: PublicationXref
    union of: UnificationXref
comment: Definition: The direct source of a pathway data or score. Usage: This does not store the trail of sources from the generation of the data to this point, only the last known source, such as a database. The XREF property may contain a publicationXref referencing a publication describing the data source (e.g. a database publication). A unificationXref may be used e.g. when pointing to an entry in a database of databases describing this database. Examples: A database, scoring method or person name.

PublicationXref
type: Class
subclass of: Xref
comment: Definition: An xref that defines a reference to a publication such as a book, journal article, web page, or software manual. Usage: The reference may or may not be in a database, although references to PubMed are preferred when possible. The publication should make a direct reference to the instance it is attached to. Publication xrefs should make use of PubMed IDs wherever possible. The DB property of an xref to an entry in PubMed should use the string "PubMed" and not "MEDLINE". Examples: PubMed:10234245

RelationshipTypeVocabulary
type: Class
subclass of: ControlledVocabulary
comment: Definition: Vocabulary for defining relationship Xref types. A reference to the PSI Molecular Interaction ontology (MI) Cross Reference type. Homepage at http://www.psidev.info/. Browse at http://www.ebi.ac.uk/ontology-lookup/browse.do?ontName=MI&termId=MI%3A0353&termName=cross-reference%20type

RelationshipXref
type: Class
subclass of: Xref
comment: Definition: An xref that defines a reference to an entity in an external resource that does not have the same biological identity as the referring entity. Usage: There is currently no controlled vocabulary of relationship types for BioPAX, although one will be created in the future if a need develops. Examples: A link between a gene G in a BioPAX data collection, and the protein product P of that gene in an external database. This is not a unification xref because G and P are different biological entities (one is a gene and one is a protein). Another example is a relationship xref for a protein that refers to the Gene Ontology biological process, e.g. 'immune response,' that the protein is involved in.

Rna
type: Class
subclass of: PhysicalEntity
subclass of: Restriction
  on property: memberPhysicalEntity
  all values from: Rna
subclass of: Restriction
  on property: entityReference
  all values from: RnaReference
comment: Definition: A physical entity consisting of a sequence of ribonucleotide monophosphates; a ribonucleic acid. Usage: RNA should be used for pools of individual RNA molecules. For describing subregions on those molecules use RNARegion. Examples: messengerRNA, microRNA, ribosomalRNA. A specific example is the let-7 microRNA.

RnaReference
type: Class
subclass of: EntityReference
subclass of: Restriction
  on property: subRegion
  all values from: RnaRegionReference
subclass of: Restriction
  on property: memberEntityReference
  all values from: RnaReference
comment: Defintion: A RNA reference is a grouping of several RNA entities that are either encoded by the same gene or replicates of the same genome. Members can differ in celular location, sequence features and bound partners. Currently conformational states (such as hairpin) are not covered.

RnaRegion
type: Class
subclass of: PhysicalEntity
subclass of: Restriction
  on property: memberPhysicalEntity
  all values from: RnaRegion
subclass of: Restriction
  on property: entityReference
  all values from: RnaRegionReference
comment: Definition: A region on a RNA molecule. Usage: RNARegion is not a pool of independent molecules but a subregion on these molecules. As such, every RNARegion has a defining RNA molecule. Examples: CDS, 3' UTR, Hairpin

RnaRegionReference
type: Class
subclass of: EntityReference
subclass of: Restriction
  on property: subRegion
  all values from: RnaRegionReference
comment: Definition: A RNA reference is a grouping of several RNA entities that are common in sequence and genomic position. Members can differ in celular location, sequence features, mutations and bound partners.

Score
type: Class
subclass of: UtilityClass
subclass of: Restriction
  on property: value
  cardinality: 1
comment: Definition: A score associated with a publication reference describing how the score was determined, the name of the method and a comment briefly describing the method. Usage: The xref must contain at least one publication that describes the method used to determine the score value. There is currently no standard way of describing values, so any string is valid. Examples: The statistical significance of a result, e.g. "p<0.05".

SequenceInterval
type: Class
subclass of: SequenceLocation
comment: Definition: An interval on a sequence. Usage: Inverval is defined as an ordered pair of SequenceSites. All of the sequence from the begin site to the end site (inclusive) is described, not any subset.

SequenceLocation
type: Class
subclass of: UtilityClass
comment: Definition: A location on a nucleotide or amino acid sequence. Usage: For most purposes it is more appropriate to use subclasses of this class. Direct instances of SequenceLocation can be used for uknown locations that can not be classified neither as an interval nor a site.

SequenceModificationVocabulary
type: Class
subclass of: ControlledVocabulary
comment: Definiiton: A reference to the PSI Molecular Interaction ontology (MI) of covalent sequence modifications. Homepage at http://www.psidev.info/. Browse at http://www.ebi.ac.uk/ontology-lookup/browse.do?ontName=MI&termId=MI%3A0252&termName=biological%20feature. Only children that are covelent modifications at specific positions can be used.

SequenceRegionVocabulary
type: Class
subclass of: ControlledVocabulary
comment: Definition: A reference to a controlled vocabulary of sequence regions, such as InterPro or Sequence Ontology (SO). Homepage at http://www.sequenceontology.org/. Browse at http://www.ebi.ac.uk/ontology-lookup/browse.do?ontName=SO

SequenceSite
type: Class
subclass of: SequenceLocation
comment: Definition: Describes a site on a sequence, i.e. the position of a single nucleotide or amino acid. Usage: A sequence site is always defined based on the reference sequence of the owning entity. For DNARegion and RNARegion it is relative to the region itself not the genome or full RNA molecule.

SmallMolecule
type: Class
subclass of: PhysicalEntity
subclass of: Restriction
  on property: feature
  all values from: BindingFeature
subclass of: Restriction
  on property: notFeature
  all values from: BindingFeature
subclass of: Restriction
  on property: entityReference
  all values from: SmallMoleculeReference
subclass of: Restriction
  on property: memberPhysicalEntity
  all values from: SmallMolecule
comment: Definition: A pool of molecules that are neither complexes nor are genetically encoded. Rationale: Identity of small molecules are based on structure, rather than sequence as in the case of DNA, RNA or Protein. A small molecule reference is a grouping of several small molecule entities that have the same chemical structure. Usage : Smalle Molecules can have a cellular location and binding features. They can't have modification features as covalent modifications of small molecules are not considered as state changes but treated as different molecules. Some non-genomic macromolecules, such as large complex carbohydrates are currently covered by small molecules despite they lack a static structure. Better coverage for such molecules require representation of generic stoichiometry and polymerization, currently planned for BioPAX level 4. Examples: glucose, penicillin, phosphatidylinositol

SmallMoleculeReference
type: Class
subclass of: EntityReference
subclass of: Restriction
  on property: memberEntityReference
  all values from: SmallMoleculeReference
comment: A small molecule reference is a grouping of several small molecule entities that have the same chemical structure. Members can differ in celular location and bound partners. Covalent modifications of small molecules are not considered as state changes but treated as different molecules.

Stoichiometry
type: Class
subclass of: UtilityClass
subclass of: Restriction
  on property: PhysicalEntity
  cardinality: 1
subclass of: Restriction
  on property: stoichiometricCoefficient
  cardinality: 1
comment: Definition: Stoichiometric coefficient of a physical entity in the context of a conversion or complex. Usage: For each participating element there must be 0 or 1 stoichiometry element. A non-existing stoichiometric element is treated as unknown. This is an n-ary bridge for left, right and component properties. Relative stoichiometries ( e.g n, n+1) often used for describin polymerization is not supported.

TemplateReaction
type: Class
subclass of: Interaction
subclass of: Restriction
  on property: participant
  all values from: PhysicalEntity
comment: Definiton: An interaction where a macromolecule is polymerized from a template macromolecule. Rationale: This is an abstraction over multiple (omitted) biochemical reactions. Ubiquitous molecules ( NTP and amino acids) consumed are also omitted. Template reaction is non-stoichiometric, does not obey law of mass conservation and temporally non-atomic. It, however, provides a mechanism to capture processes that are central to all living organisms. Usage: Regulation of TemplateReaction, e.g. via a transcription factor can be captured using TemplateReactionRegulation. TemplateReaction can also be indirect, for example it is not necessary to represent intermediary mRNA for describing expression of a protein. It was decided to not subclass TemplateReaction to subtypes such as transcription of translation for the sake of simplicity. If needed these subclasses can be added in the future. Examples: Transcription, translation, replication, reverse transcription. E.g. DNA to RNA is transcription, RNA to protein is translation and DNA to protein is protein expression from DNA.

TemplateReactionRegulation
type: Class
subclass of: Control
subclass of: Restriction
  on property: controller
  all values from: PhysicalEntity
subclass of: Restriction
  on property: controlType
  all values from: Datatype
    one of: ACTIVATION
    one of: INHIBITION
subclass of: Restriction
  on property: controlled
  all values from: TemplateReaction
comment: Definition: Regulation of the expression reaction by the controlling element such as a transcription factor or microRNA. E.g. To represent the binding of the transcription factor to a regulatory element in the TemplateReaction, create a complex of the transcription factor and the regulatory element and set that as the controller.

TissueVocabulary
type: Class
subclass of: ControlledVocabulary
comment: Definition: A reference to the BRENDA (BTO). Homepage at http://www.brenda-enzymes.info/. Browse at http://www.ebi.ac.uk/ontology-lookup/browse.do?ontName=BTO

Transport
type: Class
subclass of: Conversion
comment: Definition: An conversion in which molecules of one or more physicalEntity pools change their subcellular location and become a member of one or more other physicalEntity pools. A transport interaction does not include the transporter entity, even if one is required in order for the transport to occur. Instead, transporters are linked to transport interactions via the catalysis class. Usage: If there is a simultaneous chemical modification of the participant(s), use transportWithBiochemicalReaction class. Synonyms: translocation. Examples: The movement of Na+ into the cell through an open voltage-gated channel.

TransportWithBiochemicalReaction
type: Class
subclass of: BiochemicalReaction
subclass of: Transport
comment: Definition: A conversion interaction that is both a biochemicalReaction and a transport. In transportWithBiochemicalReaction interactions, one or more of the substrates change both their location and their physical structure. Active transport reactions that use ATP as an energy source fall under this category, even if the only covalent change is the hydrolysis of ATP to ADP. Rationale: This class was added to support a large number of transport events in pathway databases that have a biochemical reaction during the transport process. It is not expected that other double inheritance subclasses will be added to the ontology at the same level as this class. Examples: In the PEP-dependent phosphotransferase system, transportation of sugar into an E. coli cell is accompanied by the sugar's phosphorylation as it crosses the plasma membrane.

UnificationXref
type: Class
subclass of: Xref
subclass of: Restriction
  on property: id
  cardinality: 1
subclass of: Restriction
  on property: db
  cardinality: 1
comment: Definition: A unification xref defines a reference to an entity in an external resource that has the same biological identity as the referring entity Rationale: Unification xrefs are critically important for data integration. In the future they can be replaced by direct miriam links and rdf:id based identity management. Usage: For example, if one wished to link from a database record, C, describing a chemical compound in a BioPAX data collection to a record, C', describing the same chemical compound in an external database, one would use a unification xref since records C and C' describe the same biological identity. Generally, unification xrefs should be used whenever possible, although there are cases where they might not be useful, such as application to application data exchange.Identity of interactions can be computed based on the identity of its participants. An xref in a protein pointing to a gene, e.g. in the LocusLink database17, would not be a unification xref since the two entities do not have the same biological identity (one is a protein, the other is a gene). Instead, this link should be a captured as a relationship xref. References to an external controlled vocabulary term within the OpenControlledVocabulary class should use a unification xref where possible (e.g. GO:0005737). Examples: An xref in a protein instance pointing to an entry in the Swiss-Prot database, and an xref in an RNA instance pointing to the corresponding RNA sequence in the RefSeq database..

UtilityClass
type: Class
comment: Definition: This is a placeholder for classes, used for annotating the "Entity" and its subclasses but are not an "Entity" themselves. Examples include references to external databases, controlled vocabularies, evidence and provenance. Rationale: Utility classes are created when simple slots are insufficient to describe an aspect of an entity or to increase compatibility of this ontology with other standards. Usage: The utilityClass class is actually a metaclass and is only present to organize the other helper classes under one class hierarchy; instances of utilityClass should never be created.

FDA Adverse Reporting System
type: NamedIndividual
type: Public Reporting Database
comment: The FDA's Adverse Event Reporting System: http://www.fda.gov/cder/aers/default.htm

Parallel groups assignment
type: NamedIndividual
type: Non randomized Tx Assignment
comment: A pharmacokinetic clinical trial study design involving two groups of non-randomized participants where both groups recieve the purported object drug while only one group receives the purported precipitant

US Food and Drug Administration
type: NamedIndividual
type: Authoriative Organization
comment: The US Food and Drug Administration (FDA): http://www.fda.gov/opacom/hpview.html

human liver microsomes
type: NamedIndividual
type: Microsomes
comment: human liver microsomes

recombinant human cytochrome P450 isoenzymes
type: NamedIndividual
type: Recombinant Protein System
comment: recombinant human cytochrome P450 isoenzymes

simvastatin
type: NamedIndividual
type: Drug
comment: "A derivative of LOVASTATIN and potent competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HYDROXYMETHYLGLUTARYL COA REDUCTASES), which is the rate-limiting enzyme in cholesterol biosynthesis. It may also interfere with steroid hormone production. Due to the induction of hepatic LDL RECEPTORS, it increases breakdown of LDL-cholesterol (LIPOPROTEINS, LDL CHOLESTEROL)." (MeSH D019821)
unifies with x ref: unificationXref 4

unificationXref 4
type: NamedIndividual
type: UnificationXref
ID: C22028
DB: VA_NDFRT