BioPax Level 2

Go to BioPax Class:   dataSource openControlledVocabulary xref bioSource externalReferenceUtilityClass publicationXref unificationXref sequenceParticipant physicalEntityParticipant transportWithBiochemicalReaction biochemicalReaction transport complexAssembly conversion physicalEntity interaction entity pathway relationshipXref physicalInteraction smallMolecule protein rna dna complex sequenceLocation kPrime deltaGprimeO chemicalStructure experimentalForm confidence evidence utilityClass pathwayStep sequenceFeature sequenceInterval sequenceSite modulation catalysis control

Parent: externalReferenceUtilityClass

Definition: The direct source of this data. 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 or person name.

Parent: externalReferenceUtilityClass

Definition: Used to import terms from external controlled vocabularies (CVs) into the ontology. To support consistency and compatibility, open, freely available CVs should be used whenever possible, such as the Gene Ontology (GO) or other open biological CVs listed on the OBO website (http://obo.sourceforge.net/). Comment: The ID property in unification xrefs to GO and other OBO ontologies should include the ontology name in the ID property (e.g. ID="GO:0005634" instead of ID="0005634").

Parent: externalReferenceUtilityClass

Definition: A reference from an instance of a class in this ontology to an object in an external resource. Comment: Instances of the xref class should never be created and more specific classes should be used instead.

Parent: externalReferenceUtilityClass

Definition: The biological source of an entity (e.g. protein, RNA or DNA). 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). Examples: HeLa cells, human, and mouse liver tissue.

Parent: utilityClass

Definition: A pointer to an external object, such as an entry in a database or a term in a controlled vocabulary. Comment: This class is for organizational purposes only; direct instances of this class should not be created.

Parent: xref

Definition: An xref that defines a reference to a publication such as a book, journal article, web page, or software manual. 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. Comment: 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

Parent: xref

Definition: A unification xref defines a reference to an entity in an external resource that has the same biological identity as the referring entity. 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. Comment: Unification xrefs in physical entities are essential for data integration, but are less important in interactions. This is because unification xrefs on the physical entities in an interaction can be used to compute the equivalence of two interactions of the same type. 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..

Parent: physicalEntityParticipant

Definition: A DNA, RNA or protein participant in an interaction. Comment: See physicalEntityParticipant for more documentation.

Parent: utilityClass

Definition: Any additional special characteristics of a physical entity in the context of an interaction or complex. These currently include stoichiometric coefficient and cellular location, but this list may be expanded in later levels. Comment: PhysicalEntityParticipants should not be used in multiple interaction or complex instances. Instead, each interaction and complex should reference its own unique set of physicalEntityParticipants. The reason for this is that a user may add new information about a physicalEntityParticipant for one interaction or complex, such as the presence of a previously unknown post-translational modification, and unwittingly invalidate the physicalEntityParticipant for the other interactions or complexes that make use of it. Example: In the interaction describing the transport of L-arginine into the cytoplasm in E. coli, the LEFT property in the interaction would be filled with an instance of physicalEntityParticipant that specified the location of L-arginine as periplasm and the stoichiometric coefficient as one.

Parent: biochemicalReaction transport

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. Comment: 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.

Parent: conversion

Definition: A conversion interaction in which one or more entities (substrates) undergo covalent changes to become one or more other entities (products). 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.

Parent: conversion

Definition: A conversion interaction in which an entity (or set of entities) changes location within or with respect to the cell. 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. Comment: Transport interactions do not involve chemical changes of the participant(s). These cases are handled by the transportWithBiochemicalReaction class. Synonyms: translocation. Examples: The movement of Na+ into the cell through an open voltage-gated channel.

Parent: conversion

Definition: A conversion interaction in which a set of physical entities, at least one being a macromolecule (e.g. protein, RNA, DNA), aggregate via non-covalent interactions. One of the participants of a complexAssembly must be an instance of the class complex (via a physicalEntityParticipant instance). Comment: 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. 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. Note: The following are not examples of complex assembly: Covalent phosphorylation of a protein (this is a biochemicalReaction); the TFIIH complex itself (this is an instance of the complex class, not the complexAssembly class).

Parent: physicalInteraction

Definition: An interaction in which one or more entities is physically transformed into one or more other entities. Comment: This class is designed to represent a simple, single-step transformation. Multi-step transformations, such as the conversion of glucose to pyruvate in the glycolysis pathway, should be represented as pathways, if known. Since it is a highly abstract class in the ontology, instances of the conversion class should never be created. Examples: A biochemical reaction converts substrates to products, the process of complex assembly converts single molecules to a complex, transport converts entities in one compartment to the same entities in another compartment.

Parent: entity

Definition: An entity with a physical structure. A pool of entities, not a specific molecular instance of an entity in a cell. Comment: This class serves as the super-class for all physical entities, although its current set of subclasses is limited to molecules. As a highly abstract class in the ontology, instances of the physicalEntity class should never be created. Instead, more specific classes should be used. Synonyms: part, interactor, object Naming rationale: It's difficult to find a name that encompasses all of the subclasses of this class without being too general. E.g. PSI-MI uses 'interactor', BIND uses 'object', BioCyc uses 'chemicals'. physicalEntity seems to be a good name for this specialization of entity. Examples: protein, small molecule, RNA

Parent: entity

Definition: A single biological relationship between two or more entities. An interaction cannot be defined without the entities it relates. Comment: Since it is a highly abstract class in the ontology, instances of the interaction class should never be created. Instead, more specific classes should be used. Currently this class only has subclasses that define physical interactions; later levels of BioPAX may define other types of interactions, such as genetic (e.g. synthetic lethal). Naming rationale: A number of names were considered for this concept, including "process", "synthesis" and "relationship"; Interaction was chosen as it is understood by biologists in a biological context and is compatible with PSI-MI. Examples: protein-protein interaction, biochemical reaction, enzyme catalysis

Parent: owl:Thing

Definition: A discrete biological unit used when describing pathways. Comment: This is the root class for all biological concepts in the ontology, which include pathways, interactions and physical entities. As the most abstract class in the ontology, instances of the entity class should never be created. Instead, more specific classes should be used. Synonyms: thing, object, bioentity.

Parent: entity

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. Comment: It is 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'. Synonyms: network Examples: glycolysis, valine biosynthesis

Parent: xref

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. Comment: 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.

Parent: interaction

Definition: An interaction in which at least one participant is a physical entity, e.g. a binding event. Comment: This class should be used by default for representing molecular interactions, such as those defined by PSI-MI level 2. 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 sufficient information on the nature of a molecular interaction is available, a more specific BioPAX interaction class should be used. 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.

Parent: physicalEntity

Definition: Any bioactive molecule that is not a peptide, DNA, or RNA. Generally these are non-polymeric, but complex carbohydrates are not explicitly modeled as classes in this version of the ontology, thus are forced into this class. Comment: Recently, a number of small molecule databases have become available to cross-reference from this class. Examples: glucose, penicillin, phosphatidylinositol

Parent: physicalEntity

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.

Parent: physicalEntity

Definition: A physical entity consisting of a sequence of ribonucleotide monophosphates; a ribonucleic acid. Examples: messengerRNA, microRNA, ribosomalRNA. A specific example is the let-7 microRNA.

Parent: physicalEntity

Definition: A physical entity consisting of a sequence of deoxyribonucleotide monophosphates; a deoxyribonucleic acid. Comment: This is not a 'gene', since gene is a genetic concept, not a physical entity. The concept of a gene may be added later in BioPAX. Examples: a chromosome, a plasmid. A specific example is chromosome 7 of Homo sapiens.

Parent: physicalEntity

Definition: A physical entity whose structure is comprised of other physical entities bound to each other non-covalently, at least one of which is a macromolecule (e.g. protein, DNA, or RNA). 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. Comment: In general, complexes should not be defined recursively so that smaller complexes exist within larger complexes, i.e. a complex should not be a COMPONENT of another complex (see comments on the COMPONENT property). 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 and the topology of the components 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.

Parent: utilityClass

Definition: A location on a nucleotide or amino acid sequence. Comment: For organizational purposes only; direct instances of this class should not be created.

Parent: utilityClass

Definition: The apparent equilibrium constant, K', and associated values. 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][P_i]/[ATP], The concentration of ATP refers to the total concentration of all of the following species: [ATP] = [ATP^4-] + [HATP^3-] + [H₂ATP^2-] + [MgATP^2-] + [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.

Parent: utilityClass

Definition: 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 property may have multiple values, representing different measurements for delta-G'^o obtained under the different experimental conditions listed in the 5-tuple. (This definition from EcoCyc)

Parent: utilityClass

Definition: Describes a small molecule structure. 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. Comment: By virtue of the expressivity of CML, an instance of this class can also provide additional information about a small molecule, such as its chemical formula, names, and synonyms, if CML is used as the structure format. Examples: The following SMILES string, which describes the structure of glucose-6-phosphate: 'C(OP(=O)(O)O)[CH]1([CH](O)[CH](O)[CH](O)[CH](O)O1)'.

Parent: utilityClass

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

Parent: utilityClass

Definition: Confidence that the containing instance actually occurs or exists in vivo, usually a statistical measure. The xref must contain at least on publication that describes the method used to determine the confidence. There is currently no standard way of describing confidence values, so any string is valid for the confidence value. In the future, a controlled vocabulary of accepted confidence values could become available, in which case it will likely be adopted for use here to describe the value. Examples: The statistical significance of a result, e.g. "p<0.05".

Parent: utilityClass

Definition: The support for a particular assertion, such as the existence of an interaction or pathway. 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.

Parent: owl:Thing

Definition: 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. 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.

Parent: utilityClass

Definition: A step in a pathway. Comment: Multiple interactions may occur in a pathway step, each should be listed in the STEP-INTERACTIONS property. Order relationships between pathway steps may be established with the NEXT-STEP slot. This order may not be temporally meaningful for specific steps, such as for a pathway loop or a reversible reaction, but represents a directed graph of step relationships that can be useful for describing the overall flow of a pathway, as may be useful in a pathway diagram. 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.

Parent: utilityClass

Definition: A feature on a sequence relevant to an interaction, such as a binding site or post-translational modification. Examples: A phosphorylation on a protein.

Parent: sequenceLocation

Definition: Describes an interval on a sequence. All of the sequence from the begin site to the end site (inclusive) is described, not any subset.

Parent: sequenceLocation

Definition: Describes a site on a sequence, i.e. the position of a single nucleotide or amino acid.

Parent: control

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.

Parent: control

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. Comment: 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 should be created without a controller specified (i.e. the CONTROLLER property should remain empty). 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 described in a transport instance. K+ from extracellular space to cytoplasm would be described in a transport instance. The ATPase pump would be stored in a catalysis instance controlling each of the above transport instances. A biochemical reaction that does not occur by itself under physiological conditions, but has been observed to occur in the presence of cell extract, likely via one or more unknown enzymes present in the extract, would be stored in the CONTROLLED property, with the CONTROLLER property empty.

Parent: physicalInteraction

Definition: An interaction in which one entity regulates, modifies, or otherwise influences another. Two types of control interactions are defined: activation and inhibition. Comment: In general, the targets of control processes (i.e. occupants of the CONTROLLED property) should be interactions. 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 that can be ambiguous out of context. In BioPAX, this information should be captured as the kinase catalyzing (via an instance of the catalysis class) a reaction in which the substrate is phosphorylated, instead of as a control interaction in which the kinase activates the substrate. Since this class is a superclass for specific types of control, instances of the control class should only be created when none of its subclasses are applicable. Synonyms: regulation, mediation Examples: A small molecule that inhibits a pathway by an unknown mechanism controls the pathway.