TODO: Long term goals: Adding compatibility with SBML, BrainML, NeuroML various Entrez databases... TODO: Add better undestandable comments to the classes and properties from DOLCE. TODO: Representation of stoichometry through n-ary relations? TODO: Clarify the semantics of "states" in the DOLCE ontology. TODO: Change units from kJ/mol to J/mol ? TODO: Representation of conformational changes? bio-zen ontology. This ontology is under development and is NOT intended for use. Please use the BioPAX ontology instead. See: http://biopax.org Matthias Samwald 2006 For more information, visit http://neuroscientific.net TODO: Meaning of qualities of qualities? TODO: Clarify the distinctions between different 'constituent' properties. TODO: Creative Commons / Science Commons (should stay in OWL DL, though) TODO: Relationship between realness and evidence? TODO: Temporality and temporal indexing of properties? Evidence description concept A concept from 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'. Experimental modification concept A concept describing the experimental (i.e. artificial, human-made) modification of a molecule. Concept about the binding of a catalytic molecule that has modulatory effect A solution (e.g. a liquid inside a cell or inside a petri dish). Note: Things that are dissolved in the solution (e.g. a molecule population) can be described as PARTS of the solution. Abstract thing Object, feature etc. ('endurant') The main characteristic of endurants is that all of them are independent essential wholes. This does not mean that the corresponding property (being an endurant) carries proper unity, since there is no common unity criterion for endurants. Endurants can 'genuinely' change in time, in the sense that the very same endurant as a whole can have incompatible properties at different times. To see this, suppose that an endurant - say 'this paper' - has a property at a time t 'it's white', and a different, incompatible property at time t' 'it's yellow': in both cases we refer to the whole object, without picking up any particular part of it. Within endurants, we distinguish between physical and non-physical endurants, according to whether they have direct spatial qualities. Within physical endurants, we distinguish between amounts of matter, objects, and features. Definition: The support for a particular assertion, such as the existence of an interaction or pathway. Examples: A description of a molecular binding assay that was used to detect a protein-protein interaction. Formerly known as description. A unitary endurant with no mass (non-physical), generically constantly depending on some agent, on some communication act, and indirectly on some agent participating in that act. Both descriptions (in the now current sense) and concepts are non-physical objects. A quality inherent in a physical endurant. Quality of physical endurant 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][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⁺]). (Definition from EcoCyc) 1 Population of amino acids that are parts of protein molecules The location of the amino acids on the protein strands can be defined through its sequence-position (given as a number). Quality of perdurant A quality inherent in a perdurant. A quality that can be fully described by a single value. Examples: Location of an event in time, diameter of an object, velocity of an object, charge of an object. Note: The spatial location of an object in three dimensional space is not a one-dimensional-quality, because three values are needed to describe this quality. To describe spatial locations as one-dimensional-qualities, its location should be described with x, y and z coordinates according to an initial system. 1 1 1 1 Cross reference 1 A cross reference is a reference to an object in an external resource (e.g. a database entry). 1 Luminous intensity measured in candela. Unit: candela (cd). An organism. In the context of this ontology, immortalized cell-lines (e.g. HeLa cells) can be classified as organisms, too. Organism Population of nucleotides that are parts of DNA molecules 1 The location of the nucleotides on the RNA strands can be defined through its sequence-position (given as a number). For biochemical reactions, this quality refers to the standard transformed Gibbs energy change for a reaction written in terms of biochemical reactants (sums of species), delta-G'^o. UNIT: kJ/mol 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) Correlation between two qualities. Additionally to the description of correlations in MathML, this class allows the description of the correlation using concepts (e.g. "positive correlation", "negative correlation"). Correlation between two qualities 2 0 0 0 0 0 0 0 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) Ionic strength The process of the binding of molecules from different molecule populations to each other. Events of 'unbinding' (molecules that are bound lose their bonds) are also parts of such a process. If you want to emphasise that an interaction results in the formation of a complex, you should consider using the subclass complex-assembly-process instead. Definition: A process that has both a molecular-transport-process and a chemical-conversion-process as its parts. Through such a process, one or more molecules 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. 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. Molecular transport with chemical conversion process The common trait of amounts of matter is that they are endurants with no unity (according to Gangemi et a. 2001 none of them is an essential whole). Amounts of matter - 'stuffs' referred to by mass nouns like 'gold', 'iron', 'wood', 'sand', 'meat', etc. - are mereologically invariant, in the sense that they change their identity when they change some parts. A concept that can be used to describe a molecular interaction. Molecular process concept An occurrence-type is stative or eventive according to whether it holds of the mereological sum of two of its instances, i.e. if it is cumulative or not. A sitting occurrence is stative since the sum of two sittings is still a sitting occurrence.In general, events differ from situations because they are not assumed to have a description from which they depend. They can be sequenced by some course, but they do not require a description as a unifying criterion.On the other hand, at any time, one can conceive a description that asserts the constraints by which an event of a certian type is such, and in this case, it becomes a situation.Since the decision of designing an explicit description that unifies a perdurant depends on context, task, interest, application, etc., when aligning an ontology do DLP, there can be indecision on where to align an event-oriented class. For example, in the WordNet alignment, we have decided to put only some physical events under 'event', e.g. 'discharge', in order to stress the social orientedness of DLP. But whereas we need to talk explicitly of the criteria by which we conceive discharge events, these will be put under 'situation'.Similar considerations are made for the other types of perdurants in DOLCE.A different notion of event (dealing with change) is currently investigated for further developments: being 'achievement', 'accomplishment', 'state', 'event', etc. can be also considered 'aspects' of processes or of parts of them. For example, the same process 'rock erosion in the Sinni valley' can be conceptualized as an accomplishment (what has brought the current state that e.g. we are trying to explain), as an achievement (the erosion process as the result of a previous accomplishment), as a state (if we collapse the time interval of the erosion into a time point), or as an event (what has changed our focus from a state to another).In the erosion case, we could have good motivations to shift from one aspect to another: a) causation focus, b) effectual focus, c) condensation d) transition (causality).If we want to consider all the aspects of a process together, we need to postulate a unifying descriptive set of criteria (i.e. a 'description'), according to which that process is circumstantiated in a 'situation'. The different aspects will arise as a parts of a same situation. Concept The concentration of physical entities in a solution, measured in moles. Units: mol/L Concentration Mass measured in kilograms. Unit: kilogram (kg). Mass Temperature measured in Kelvin. Unit: Kelvin. Temperature Within stative occurrences, we distinguish between states and processes according to homeomericity: sitting is classified as a state but running is classified as a process, since there are (very short) temporal parts of a running that are not themselves runnings. In general, processes differ from situations because they are not assumed to have a description from which they depend. They can be sequenced by some course, but they do not require a description as a unifying criterion. On the other hand, at any time, one can conceive a description that asserts the constraints by which a process of a certian type is such, and in this case, it becomes a situation. Since the decision of designing an explicit description that unifies a perdurant depends on context, task, interest, application, etc., when aligning an ontology do DLP, there can be indecision on where to align a process-oriented class. For example, in the WordNet alignment, we have decided to put only some physical processes under 'process', e.g. 'organic process', in order to stress the social orientedness of DLP. But whereas we need to talk explicitly of the criteria by which we conceive organic processes, these will be put under 'situation'. Similar considerations are made for the other types of perdurants in DOLCE. A different notion of event (dealing with change) is currently investigated for further developments: being 'achievement', 'accomplishment', 'state', 'event', etc. can be also considered 'aspects' of processes or of parts of them. For example, the same process 'rock erosion in the Sinni valley' can be conceptualized as an accomplishment (what has brought the current state that e.g. we are trying to explain), as an achievement (the erosion process as the result of a previous accomplishment), as a state (if we collapse the time interval of the erosion into a time point), or as an event (what has changed our focus from a state to another). In the erosion case, we could have good motivations to shift from one aspect to another: a) causation focus, b) effectual focus, c) condensation d) transition (causality). If we want to consider all the aspects of a process together, we need to postulate a unifying descriptive set of criteria (i.e. a 'description'), according to which that process is circumstantiated in a 'situation'. The different aspects will arise as a parts of a same situation. URL Sequence type or feature concept pH 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) A 'subsequence-part' of a macromolecule is a part of a molecule to which we can assign a sequence (which is a subsequence of the sequence of the whole macromolecule). Definition: A process in which at least one participant is a molecule or a part of a molecule, e.g. a binding event. 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. Spatio-temporal-particular (a particular thing located in certain places at certain times) Dummy class for optimizing some property universes. It includes all entities that are not reifications of universals ('abstracts'), i.e. those entities that are in space-time. 0 Uncatalyzed (spontaneous) chemical conversion process. Organismal classification concept A concept from the taxonomy of species in biology (e.g. Homo, Homo sapiens, Rattus, Eukaryota). Features that are relevant parts of their host, like a bump or an edge. Qualities can be seen as the basic entities we can perceive or measure: shapes, colors, sizes, sounds, smells, as well as weights, lengths, electrical charges... 'Quality' is often used as a synonymous of 'property', but this is not the case in this upper ontology: qualities are particulars, properties are universals. Qualities inhere to entities: every entity (including qualities themselves) comes with certain qualities, which exist as long as the entity exists. Quality Concept describing a certain database Examples: 'Uniprot', 'Ensembl', 'Entrez Gene' are examples for biological database systems. 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) The measured equilibrium constant for a biochemical reaction, encoded by the slot KEQ, is actually the apparent equilibrium constant, K'. UNIT: (dimensionless) 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) Molecular function concept Concept describing a cell type (e.g. "hepatocyte", "neuron", "HeLa cell"). Celltype concept A concept from the general lexical reference system Wordnet. See http://wordnet.princeton.edu/ Concept from Wordnet Population of either molecules, molecular complexes, parts of molecules or parts of molecular complexes A concept about a correlation (e.g. 'positive correlation', 'negative correlation'). Correlation concept An endurant with no mass, generically constantly depending on some agent. Non-physical endurants can have physical constituents (e.g. in the case of members of a collection). A concept that describes the type of a molecular interaction (e.g. van-der-Waals interactions, ionic interactions). Molecular binding type concept AKA arbitrary-collection.The mereological sum of any two or more endurants (physical or not). Arbitrary sums have no unity criterion (they are 'extensional'). Chemical conversion process A process in which molecules undergo covalent changes to become other molecules (thereby becoming part of another molecule population). Examples: ATP + H2O = ADP + Pi Note: 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. 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. 1 1 Species A species, e.g. 'Homo sp.', 'Homo sapiens', 'Rattus rattus', 'Arabidopsis thaliana'. Biological process type (concept) Mean molecular mass of molecules in population of molecules / molecular complexes Instances of this class describe observed correlations between qualities. Optionally, this can contain MATHEMATICAL correlations expressed in MathML that can be used for numeric simulation. Exemplary use cases: "Concentration of metabolite A is positively correlated with concentration of metabolite B", "Concentration of metabolite A is negatively correlated with the conversion rate of the enzymatic reaction B", "The rate of influx of metabolite A into compartment B is equal to 123,4 times the first derivative of the concentration of metabolite B minus the second derivative of the concentration of metabolite C" etc. Additionally to the description of correlations in MathML, this class allows the description of the correlation using concepts (e.g. "positive correlation", "negative correlation"). 1 1 1 1 1 1 1 1 An observed correlation of the qualities of some things. 1 2 Definition: A molecular-binding-process in which molecules from different molecule populations, at least one being a population of macromolecules (e.g. protein, RNA, DNA), aggregate via non-covalent interactions. One of the participants of molecular-binding-process must be an instance of the class complex-population. 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). A process that has several molecular interaction processes as its parts, 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, synthesis of serotonin from tryptophan. Chemical pathway Electrical current (quality) Electrical current measured in Ampere. Unit: Ampere (A). A concept from the sequence ontology. See http://song.sourceforge.net/ Definition of RNA: 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. Population of RNA molecules. Molecular transport process A process in which molecules of a certain molecule population change their location and become part of another molecule population (which is located elsewhere). Transporters are linked to transport interactions via the catalyzed-by property. Synonyms: translocation. Examples: The exocytosis of a neurotransmitter from a cellular vesicle into the synaptic cleft. A concept from the EC nomenclature of enzymes / enzymatic reactions. The EC number is a unique number assigned to a reaction or an enzyme by the Enzyme Commission of the International Union of Biochemistry and Molecular Biology. Concept from EC enzyme nomenclature pMg A measure of the concentration of magnesium (Mg) in solution. (pMg = -log₁₀[Mg²⁺]) A population of either molecules, molecular complexes, parts of molecules, parts of molecular complexes A 'subsequence-part' of a macromolecule is a part of a molecule to which we can assign a sequence (which is a subsequence of the sequence of the whole macromolecule). Each subsequence-part of a molecule has two sequence-sites as boundaries. Perdurants (AKA occurrences) comprise what are variously called events, processes, phenomena, activities and states. They can have temporal parts or spatial parts. For instance, the first movement of (an execution of) a symphony is a temporal part of the symphony. On the other hand, the play performed by the left side of the orchestra is a spatial part. In both cases, these parts are occurrences themselves. We assume that objects cannot be parts of occurrences, but rather they participate in them. Perdurants extend in time by accumulating different temporal parts, so that, at any time they are present, they are only partially present, in the sense that some of their proper temporal parts (e.g., their previous or future phases) may be not present. E.g., the piece of paper you are reading now is wholly present, while some temporal parts of your reading are not present yet, or any more. Philosophers say that endurants are entities that are in time, while lacking temporal parts (so to speak, all their parts flow with them in time). Perdurants, on the contrary, are entities that happen in time, and can have temporal parts (all their parts are fixed in time). Event, process, state etc. ('perdurant') Small molecule concept Definition: Describes a small molecule, optionally giving its structure. A physical quality, q-located in (whose value is given within) ordinary spaces (geographical coordinates, cosmological positions, anatomical axes, etc.). An endurant having a direct physical (at least spatial) quality. Catalyzed chemical conversion process 1 Population of molecules A genus, e.g. 'Homo', 'Rattus' or 'Escherichia'. Genus The duration of a perdurant. UNIT: s Duration The location of the nucleotides on the DNA strands can be defined through its sequence-position (given as a number). Population of nucleotides that are parts of DNA molecules 1 Features are 'parasitic entities', that exist insofar their host exists. Typical examples of features are holes, bumps, boundaries, or spots of color. Features may be relevant parts of their host, like a bump or an edge, or dependent regions like a hole in a piece of cheese, the underneath of a table, the front of a house, or the shadow of a tree, which are not parts of their host. All features are essential wholes, but no common unity criterion may exist for all of them. However, typical features have a topological unity, as they are singular entities.Here only features of physical endurants are considered. Length measured in meters. Unit: meter (m). Population of DNA molecules Definition of DNA: 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. Note: This should NOT be used to refer to e.g. a chromosome! A chromosome has many other parts (histones etc.) that are not part of the DNA (which is a polymer of amino acids). DNA is a physical part of a chromosome. A temporal location quality. A feature that is not part of its host, like a hole in a piece of cheese, the underneath of a table, the front of a house, or the shadow of a tree. Population of parts of RNA molecules Within stative occurrences, we distinguish between states and processes according to homeomericity: sitting is classified as a state but running is classified as a process, since there are (very short) temporal parts of a running that are not themselves runnings.In general, states differ from situations because they are not assumed to have a description from which they depend. They can be sequenced by some course, but they do not require a description as a unifying criterion.On the other hand, at any time, one can conceive a description that asserts the constraints by which a state of a certian type is such, and in this case, it becomes a situation.Since the decision of designing an explicit description that unifies a perdurant depends on context, task, interest, application, etc., when aligning an ontology do DLP, there can be indecision on where to align a state-oriented class. For example, in the WordNet alignment, we have decided to put only some physical states under 'state', e.g. 'turgor', in order to stress the social orientedness of DLP. But whereas we need to talk explicitly of the criteria by which we conceive turgor states, these will be put under 'situation'.Similar considerations are made for the other types of perdurants in DOLCE.A different notion of event (dealing with change) is currently investigated for further developments: being 'achievement', 'accomplishment', 'state', 'event', etc. can be also considered 'aspects' of processes or of parts of them. For example, the same process 'rock erosion in the Sinni valley' can be conceptualized as an accomplishment (what has brought the current state that e.g. we are trying to explain), as an achievement (the erosion process as the result of a previous accomplishment), as a state (if we collapse the time interval of the erosion into a time point), or as an event (what has changed our focus from a state to another).In the erosion case, we could have good motivations to shift from one aspect to another: a) causation focus, b) effectual focus, c) condensation d) transition (causality).If we want to consider all the aspects of a process together, we need to postulate a unifying descriptive set of criteria (i.e. a 'description'), according to which that process is circumstantiated in a 'situation'. The different aspects will arise as a parts of a same situation. Concept from MeSH A concept from the Medical Subject Headings - taxonomy. See http://www.nlm.nih.gov/mesh/meshhome.html For biochemical reactions, this quality refers to the standard transformed enthalpy change for a reaction written in terms of biochemical reactants (sums of species), delta-H'^o. UNIT: kJ/mol delta-G'^o = delta-H'^o - T delta-S'^o (This definition from EcoCyc) delta-H (enthalpy difference) Stoichiometry The stoichiometry of a chemical reaction regarding to one of the reaction participants. 1 NOTE: Parts of a complex should be defined via its 'proper-part' property. NOTE: 'Sub-complexes' should not be defined in this ontology. 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. Comment: Complexes cannot be defined recursively so that smaller complexes exist within larger complexes. 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 instances of this class. Examples: Ribosome, RNA polymerase II. Other examples of this class include complexes of multiple protein monomers and complexes of proteins and small molecules. Population of molecular complexes Cell (in the biological sense) Quality of non-physical endurant A quality inherent in a non-physical endurant. Chemical reaction direction and speed The speed and direction of a chemical reaction UNIT: mol/h (Mol per hour) NOTE: Positive values mean that the direction of the direction is from 'left' to 'right', negative values meant that the direction is 'right' to 'left'. NOTE: When a reaction is in equilibrium, this value should be 0. An occurrence-type is stative or eventive according to whether it holds of the mereological sum of two of its instances, i.e. if it is cumulative or not. A sitting occurrence is stative since the sum of two sittings is still a sitting occurrence. A 'subsequence-part' of a macromolecule is a part of a molecule to which we can assign a sequence (which is a subsequence of the sequence of the whole macromolecule). Population of subsequence-parts of DNA molecules. AKA 'entity'.Any individual in the DOLCE domain of discourse. The extensional coverage of DOLCE is as large as possible, since it ranges on 'possibilia', i.e all possible individuals that can be postulated by means of DOLCE axioms. Possibilia include physical objects, substances, processes, qualities, conceptual regions, non-physical objects, collections and even arbitrary sums of objects.The class 'particular' features a covering partition that includes: endurant, perdurant, quality, and abstract. There are also some subclasses defined as unions of subclasses of 'particular' for special purposes: spatio-temporal-particular (any particular except abstracts)- physical-realization (any realization of an information object, defined in the ExtendedDnS ontology). Tissue (biological) A compartment in the biological is in most cases a structure filled with liquid that is confined by a tight barrier. Note: Things that are inside the compartment can be described as PARTS of the compartment. Biological compartment (including its contents) Definition: A xref that represents 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. Publication cross reference Population of parts of small molecules The main characteristic of physical objects is that they are endurants with unity. However, they have no common unity criterion, since different subtypes of objects may have different unity criteria. Differently from aggregates, (most) physical objects change some of their parts while keeping their identity, they can have therefore temporary parts. Often physical objects (indeed, all endurants) are ontologically independent from occurrences (discussed below). However, if we admit that every object has a life, it is hard to exclude a mutual specific constant dependence between the two. Nevertheless, we may still use the notion of dependence to (weakly) characterize objects as being not specifically constantly dependent on other objects. Population of parts of DNA molecules Population of parts of protein molecules Population of protein molecules. Definition of protein: 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. Cellular component type (concept) Definition of a small molecule: 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 Population of small molecules Population of parts of molecules A 'population of parts of molecules' can be thought of as a population of many similar sites on molecules in a molecule-population. Note: this refers to populations of molecular parts, NOT to sub-populations of molecular-populations. An extension of the 'skos:broader' property to specify an instantiation (instance of) relationship between two concepts. broader (instantive) Temporal connection between perdurants: p1 ending part is connected to p2 beginning part. This is a superproperty of the 'described-by' and the 'narrower' property. It can be used to make the broader/narrower - hierarchies of SKOS accessible for automated reasoning about entities annotated with a SKOS concept. described by OR narrower Broader concepts are typically rendered as parents in a concept hierarchy (tree). has broader correlates quality AKA 'co-occurs'. Temporal coincidence between perdurants. broader (generic) An extension of the 'broader' property to specify the class subsumption (sub-class/super-class) relationship between two concepts. Any cofactor(s) or coenzyme(s) required for catalysis of the (probably enzymatic) chemical-reaction-event. causes The immediate relation holding between endurants and perdurants (e.g. in 'the car is running').Participation can be constant (in all parts of the perdurant, e.g. in 'the car is running'), or temporary (in only some parts, e.g. in 'I'm electing the president').A 'functional' participant is specialized for those forms of participation that depend on the nature of participants, processes, or on the intentionality of agentive participants. Traditional 'thematic role' should be mapped to functional participation.For relations holding between participants in a same perdurant, see the co-participates relation. This important property should be used to relate things to 'clones' of these things we have made in OWL. Example: A biological sequence database holds many sequences of proteins from the human proteome (in the form of sequence-qualities that are not assigned to any particular protein). A scientist wants to describe the sequence of a certain protein he is investigating, and thinks that the sequence-quality of this protein is similar to the sequence-quality described in the sequence database. He makes a copy of the sequence-quality and assigns this quality to his protein. In order to state that this new sequence quality was derived from the database, he adds a statement like '{copied-sequence-quality} inf:prototype {sequence-quality-in-database}' The relation between an entity (playing the role of example, sample, prototype, master, etc.), and another that has all the properties of the first (or a given set of them), except space-time. The description of the first entity should be 'sharper' or at least 'more accurate' than that of the prototype. is a digital representation of can be downloaded from related to Having the same parts at time t. 'Constituent' should depend on some layering of the ontology. For example, scientific granularities or ontological 'strata' are typical layerings. A constituent is a part belonging to a lower layer. Since layering is actually a partition of the ontology, constituents are not properly classified as parts, although this kinship can be intuitive for common sense. Example of specific constant constituents are the entities constituting a setting (a situation), whilethe entities constituting a collection are examples of generic constant constituents. The basic connection, not requiring a common boundary. Temporal overlap: having a (partly) common temporal location. Any mediated relation that composes temporal locations of perdurants with mereotopological relations between those locations.Mereotopological relations are those specified in the J. Allen's theory of time intervals. coincidence of life The most generic location relation, probably equivalent to more than one image schema in a cognitive system (e.g. containment for exact location, proximity for approximate location).This is meant to reason on generalized, common sense as well as formal locations, including naive localization, between any kinds of entities. Generic location is branched into 'exact' location, ranging on regions, and 'approximate' (naive) location, ranging on non-regions. exemplary part A part that is in fact one of many ('uncountable') similar parts. Example: "<liver-tissue> <exemplary-part> <typical-liver-cell>". typical-liver-cell here stands as an example for many other, similar liver cells that are also part of the liver-tissue, but which are not described. The most generic part relation, reflexive, asymmetric, and transitive. described by semantic relation This property should not be used directly, but as a super-property for all properties denoting a relationship of meaning between concepts. 'Constituent' should depend on some layering of the ontology. For example, scientific granularities or ontological 'strata' are typical layerings. A constituent is a part belonging to a lower layer. Since layering is actually a partition of the ontology, constituents are not properly classified as parts, although this kinship can be intuitive for common sense. Example of specific constant constituents are the entities constituting a setting (a situation), whilethe entities constituting a collection are examples of generic constant constituents. catalyzed by By strong connection here we mean a connection between two entities that share a boundary. Anytime x is present, x has participant y. In other words, all parts of x have a same participant.Participation can be constant (in all parts of the perdurant, e.g. in 'the car is running'), or temporary (in only some parts, e.g. in 'I'm electing the president'). A composed (mediated) relation used here to make relations 'temporary': by adding it as a superrelation, the effect is that the two related endurants cannot be present at all the same time intervals, but are compresent at least at some time interval (see related axiom).In FOL, the same constraint can be stated directly by coreference.This workaround can be used to index time of relations that involve reciprocal dependency, but it cannot be used in general with relations involving multiple strata of reality. For example, _about_ relation can be temporally indexed, without involving that the time of the information object overlaps with the time of the entity the information is about (but this works for e.g. the _realizes_ relation between information objects and entities whatsoever). The different temporal constraints of about vs. expresses probably derive from the dependency of aboutness from conception (to be about x, an information object should also express a description d that is satisfied by a situation including x, then temporal overlapping of _about_ is true in virtue of d). On the other hand, even conceives cannot be indexed in this way, because overlapping does not hold between the time og the conceiving agent, and the conceived description (or situation). Mereological sibling: having a common whole Scientific evidence supporting the existence of the entity as described. Being part at time t. It holds for endurants only. This is important to model parts that can change or be lost over time without affecting the identity of the whole. In FOL, this is expressed as a ternary relation, but in DLs we only can reason with binary relations, then only the necessary axiom of compresence is represented here. Mereological overlap: having a common part. in regards to This property is the inverse of the 'broaderInstantive' property. narrower (instantive) This property is the inverse of the 'broaderPartitive' property. narrower (partitive) The the value of this property is a string in InChI format describing a molecular structure (see URL http://www.iupac.org/inchi/ for more info). has sequence end position filesize (in byte) A reference to a related resource. Relation A subjective metric that lets users state how interesting or meaningul they find an entity. The value should lie between (inclusively) 0 and 1. Scores for interestingness and realness can be meaningfully combined. For instance, an interesting but unproven new theory might be assigned a high interestingness score but a low realness score. interestingness preferred label has sequence start position A date associated with an event in the life cycle of the resource. Date The value of this property should be a string describing a 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. Resource Type The nature or genre of the content of the resource. An entity responsible for making contributions to the content of the resource. Contributor A reference to a resource from which the present resource is derived. Source alternative label Coverage The extent or scope of the content of the resource. Title A name given to the resource. The the value of this property is a string in SMILES format describing the structure of a molecule (see URL www.daylight.com/dayhtml/smiles/ for more info). The the value of this property is a string in CML format for the description of molecular structures (see URL http://www.xml-cml.org for more info). Creator An entity primarily responsible for making the content of the resource. standard deviation of value A metric to state how valid the assertions made by an entity are, i.e. how probable it is that this entity is really found in nature. The value should lie between (inclusively) 0 and 1. If a user applies a realness-value of 1 to an entity this essentially means that he or she is sure that the entity exists in nature. Lower values mean that he or she is less certain. A value of 0 means that the entity is not a valid representation of reality at all. However, this should NOT be understood as a NEGATION of any assertions we can associate with the entity. It just means that the entity described in OWL is useless for our understanding of reality. Scores for interestingness and realness can be meaningfully combined. For instance, an interesting but unproven new theory might be assigned a high interestingness score but a low realness score. Description An account of the content of the resource. An entity responsible for making the resource available Publisher The primary identifier in the external database of the object to which this xref refers. Subject and Keywords The topic of the content of the resource. 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. has sequence length Length of the sequence of a polymer (i.e. the number of monomers that make up the polymer). Language A language of the intellectual content of the resource. has constant value This property can be used to state that a quality has a constant value (i.e. the value does not change in the whole existance of the quality). sha-1 checksum maximum deviation of value has initial value TODO: Write better comment / description This value is the initial value of the quality (e.g. a concentration). 'Initial' here means at the start of the life of the quality. A mathematical description of the correlation of one-dimensional-qualities in MathML (using variables A, B, C, D, E, F, G, H and I). An unambiguous reference to the resource within a given context. Resource Identifier has sequence position Rights Management Information about rights held in and over the resource. Format The physical or digital manifestation of the resource. Temporal precedence between two perdurants. No further dependence is implied (e.g. mereological, causal). Narrower concepts are typically rendered as children in a concept hierarchy (tree). has narrower broader (partitive) An extension of the 'broader' property to specify a partitive (part of) relationship between two concepts. All temporal locations of perdurant x are also temporal locations of perdurant y. This property is the inverse of the 'broaderGeneric' property. narrower (generic) Used when an annotation is made based on a method that precipitates a multivalent antigen by a bivalent antibody. inferred from immunoprecipitation inferred from ligand binding inferred from direct assay traceable author statement Evidence_Codes_Ontology inferred from experiment inferred from physical interaction inferred from protein assay inferred from immunological assay inferred from co-immunoprecipitation Used when an annotation is based on the interaction of one gene product with another in a co-immunoprecipitation assay (two or more proteins are precipitated when treated with an antibody specific to a single protein). The interacting protein is referenced in the evidence_with column. inferred from protein localization inferred from localization of fusion protein inferred from array experiment inferred from Nimblegen array Caenorhabditis elegans inferred from protein:ion binding assay inferred from protein binding Used in component annotations when a subunit is isolated as part of purification of its larger complex. inferred from co-purification inferred from similarity inferred from in-silico analysis Used when an annotation is made based on the sequence similarity of the annotated gene/gene product to a single other gene or group of genes and this evidence has been examined by a curator. inferred from sequence similarity inferred from cDNA microarray inferred from nucleic acid binding assay inferred from Southwestern analysis Used when an annotation is made based on a Southwestern blot analysis, which detects DNA binding of proteins using labeled DNA as probe hybridizing to electrophoretically separated proteins. inferred from specific protein inhibition inferred from level of protein expression inferred from protein expression inferred from expression pattern inferred from genetic analysis inferred from phenotype inferred from RNAi experiment Inference based on a phenotype observed when expressing an RNAi construct that includes a fragment of the gene product in a wild-type (for that gene product) background. A double-stranded RNA specifically suppresses the expression of the gene bearing its complementary sequence. inferred from in vitro binding assay inferred from motif similarity Used when an annotation is made based on the presence of a recognized domain or motif in a gene product's (usually protein) primary sequence. inferred from electrophysiological experiment inferred from two-electrode voltage clamp technique Used when an annotation is based on the interaction of protein with another in a far-Western assay. The assay involves separating target proteins on an SDS-PAGE gel, blotting to a membrane, hybridization with a protein probe and visualization using a probe-directed antibody. The interacting protein is referenced in the evidence_with column. inferred from far-Western assay inferred from nucleic acid hybridization Used when an annotation is made based on results of a subtractive hybridization experiment that demonstrates expression of an RNA under one condition and not another. inferred from transcript expression inferred from subtractive hybridization Positive correlation (signed) Signed positive correlation: A ~ B inferred from Northwestern analysis Used when an annotation is made based on a Northwestern blot analysis, which detects RNA binding of proteins using labeled RNA as probe hybridizing to electrophoretically separated proteins. Used when an annotation is based on the hybridization of a probe derived from the gene in question with a gene of known function/process/component. Can also be used when a probe derived from a gene of known function/process/component hybridizes with the gene in question. inferred from Southern blot hybridization inferred from level of transcript expression inferred from differential methylation hybridization inferred from reconstitution assay INHIBITION INHIBITION-COMPETITIVE INHIBITION-OTHER INHIBITION-UNCOMPETITIVE ACTIVATION-ALLOSTERIC ACTIVATION-NONALLOSTERIC INHIBITION-NONCOMPETITIVE INHIBITION-IRREVERSIBLE INHIBITION-ALLOSTERIC ACTIVATION inferred from split-ubiquitin assay Used when an annotation is based on the interaction of two proteins in a split-ubiquitin assay. The bait protein is fused to the C-terminal ubiquitin (Cub) domain followed by a reporter protein, and the prey protein is fused to a mutated N terminal ubiquiting (NubG) domain. If bait and prey interact, their interaction brings the NubG and Cub domains close enough together to reconstitute split-ubiquitin, resulting in the release of the reporter protein by the action of the UBPs. EQUAL LESS-THAN GREATER-THAN Used when a component annotation is made based on the presence of a targeting sequence in a protein's primary sequence. The presence of the targeting sequence may be detected by computational prediction and/or the author's manual examination of the sequence. inferred from targeting sequence prediction inferred from curated BLAST match inferred from curated BLAST match to protein inferred from Sos-recruitment assay Used when an annotation is based on the interaction of two proteins in a sos-recruitment assay. The assay is a genetic screening system that detects protein-protein interactions and is not based on a transcriptional readout. inferred from transcription assay PHYSIOL-RIGHT-TO-LEFT IRREVERSIBLE-LEFT-TO-RIGHT IRREVERSIBLE-RIGHT-TO-LEFT PHYSIOL-LEFT-TO-RIGHT REVERSIBLE inferred from localiztion of GUS fusion protein inferred from localization of lacZ fusion protein inferred from InterPro motif similarity inferred from immunogold labelling Used when an annotation is made based on immunolocalization method that detects an antigen in cytological preparations by using a gold-labeled secondary antibody. Positive correlation (unsigned) Unsigned Positive correlation: |A| ~ |B| inferred from reviewed computational analysis Used when an annotation is made solely based on a computational analysis of the gene product's sequence. The prediction has not been examined by a curator. inferred from electronic annotation Used for: Predictions based on large-scale experiments (e.g. genome-wide two-hybrid, genome-wide synthetic interactions); Predictions based on integration of large-scale datasets of several types; Text-based computation (e.g. text mining). This code is used for annotations based on a non-sequence-based computational method, where the results have been reviewed by an author or a curator. IEA should be used for any computational annotations that are not checked for accuracy by a curator (or by the authors of a paper describing such analysis), and sequence comparisons that have been reviewed use ISS. For microarray results alone, IEP is preferred, but RCA is used when microarray results are combined with results of other types of large-scale experiments.n inferred from protein separation inferred from fractionation inferred from transport assay Used when an annotation is made based on a functional complementation assay in which a wild-type copy of the gene in question is inserted into a mutant background in the organism of the gene's origin or a heterologous organism with a mutation in the homologous gene. inferred from functional complementation inferred from genetic interaction Arabidopsis thaliana inferred from PCR experiment inferred from genomic analysis inferred from RT-PCR experiment inferred from protein separation followed by fragment identification inferred from uptake assay in a heterologous system Used when an annotation is made based on small molecule update assays carried out in a heterologous system that contains a recombinant protein. inferred from mutant phenotype inferred from loss-of-function mutant phenotype inferred from transient rescue 0.0 A quality that always has the value 0. inferred from over expression Used when an annotation is made based on the analysis of the phenotype of a wild-type or mutant transgenic organism that has been engineered to overexpress the gene product in question. inferred from ribohomopolymer binding assay inferred from Affymetrix array inferred from immunolocalization Used when an annotation is maded based on methods that detect the presence of macromolecules, proteins, and compounds by the use of antibodies. inferred from immunolocalization of epitope-tagged protein Used when an annotation is maded based on immunolocalization of recombinant proteins fused with epitopes that are recognized by antibodies. Used when an annotation is made for a gene product that has not been cloned but is associated with a quantitative trait locus. inferred from quantitative trait analysis inferred from thin layer chromatographic assay inferred by curator To be used for those cases where an annotation is not supported by any evidence, but can be reasonably inferred by a curator from other GO annotations, for which evidence is available. inferred from gain-of-function mutant phenotype inferred from protein separation followed by direct sequencing inferred from amplification of intermethylated sites inferred from CpG island microarray experiment Used when an annotation is maded based on fractionation of a protein with other compounds, factors, or macromolecules. inferred from co-fractionation inferred from expression microarray experiment Used when an annotation is made based on levels of RNA expression determined by microarray experiment. inferred from level of transcript expression determined by microarray analysis Signed negative correlation: A ~ (-B) Negative correlation (signed) inferred from spatial pattern of protein expression Used when an annotation is based on a phenotype observed when expressing an anti-sense version of a gene product in a wild-type (for that gene product) background. inferred from anti-sense experiment inferred from localization of GFP fusion protein Used when an annotation is made based on levels of RNA expression determined by a Northern blot experiment. inferred from level of transcript expression determined by Northern assay inferred from protein expression in heterologous system Used when an annotation is made based on electrophoretic mobility shift of macromolecules, compounds, and proteins. Most commonly used for detecting the binding of protein to DNA. inferred from electrophoretic mobility shift assay Used when an annotation is made based on a functional complementation assay in which a wild-type copy of the gene in question is inserted into a heterologous organism with a mutation in the homologous gene. inferred from functional complemtation in heterologous system inferred from level of transcript expression determined by RT-PCR Used when an annotation is made based on levels of RNA expression determined by an RT-PCR experiment (quantitative or otherwise). inferred from epistatic interaction Used when an annotation is based on results of epistatis analysis of an allele of the gene in question and a mutant allele at another locus. inferred from curated BLAST match to nucleic acid inferred from double mutant analysis Used when an annotation is made based on the phenotype of double mutant organism that contains a mutation in the gene product of interest in addition to a second mutation at an unrelated locus. inferred from in vitro transcription reconstitution assay Reactome Used when an annotation is made based on levels of RNA expression determined by an RNA protection assay. inferred from RNA protection assay Homo sapiens Used when an annotation is made based on assays using living organisms to measure the effect of a substance, factor, or condition. inferred from bioassay inferred from structural similarity Used when an annotation is made based on the structural similarity of the annotated gene/gene product to a single other gene or group of genes. In the case of a single gene, an accession for the related gene's sequence is entered in the evidence_with field. Used when an annotation is maded based on separation of subcellular components based on their physical properties, such as density in sucrose density gradients. This evidence is used mostly for annotations to the cellular component ontology. inferred from cell fractionation Used for annotations based on statements in a publication or database record where the curator cannot, from the publication, trace the primary source of the evidence. non-traceable author statement inferred from localization of YFP fusion protein inferred from reporter gene assay Used when an annotation is made on the basis of the expression pattern of a reporter gene. The reporter gene may consist of the native promoter of the gene in question that drives the expression of a readily assayable gene product such as GUS or GFP. The reporter gene may also be a marker of a particular type of physiological response. inferred from hybrid interaction Used when an annotation is made based on levels of protein expression determined by a Western blot assay. inferred from Western blot assay inferred from spatial pattern of transcript expression inferred from affinity chromatography Used when an annotation is made based on affinity chromatography, which is a selective separation technique by which a compound (e.g., an antibody) is immobilized on a polymeric matrix and used to bind selectively other compounds. Following removal of the unattached components, the bound compound is displaced by changing the concentration of protons, salts, or cofactors in the eluent. inferred from in vitro transcription reconstitution assay with recombinant protein Negative correlation (unsigned) Unsigned negative correlation: |A| ~ |B| * (-1) inferred from methylation-specific PCR Used when an annotation is made on the basis of a protein expression library screen where a protein of interest is isolated on the basis of its hybridization to an antibody raised to a homologous protein. inferred from expression library screening inferred from supressor/enhancer interaction inferred from restriction landmark genomic scanning inferred from transcriptional activation assay Used when an annotation is maded based on assays that show transcriptional activation of a specific target reporter gene. Used when an annotation is made based on the visual examination of a mutant phenotype; for example, abnormalities in organism morphology. inferred from visible phenotype Rattus sp. inferred from enzyme assay Used when an annotation is maded based on assays that determine the catalytic activity of enzymes. inferred from differential hybridization Used when an annotation is made based on results of a differential hybridization experiment that demonstrates expression of an RNA under one condition and not another. InChI SMILES CML no biological data Escherichia coli Used when an annotation is maded based on methods that detect the presence of macromolecules, proteins, and compounds by the use of a fluorescent-labeled antibody. inferred from immunofluorescence not_recorded inferred from ectopic expression Used when an annotation is made based on the analysis of the phenotype of a wild-type or mutant transgenic organism that has been engineered to overexpress or ectopically express the gene product in question. Used when an annotation is made based on the analysis of a biochemical aspect of a mutant phenotype; for example, the accumulation of a biosynthetic intermediate. inferred from biochemical trait Pubmed inferred from physiological response Used when an annotation is made based on the physiological response of a mutant to an external stimulus; for example, abnormal growth of the root in response to gravity, delay in flowering in response to varying light conditions. inferred from in situ hybridization Used when an annotation is made based on a method that hybridizes a labeled nucleic acid probe to a tissue or cell specimen in which the cellular structures are still intact. Depending on the label and protocol used, the probe may detect complementary DNA or RNA by hybridizing specifically to that gene or sequence. inferred from genomic microarray experiment BIND (Biomolecular Interaction Network Database) inferred from transmembrane domain prediction Used when a component annotation is made based on the presence of one or more transmembrane domains in a protein's primary sequence. The presence of the transmembrane domains may be detected by computational prediction and/or the author's manual examination of the sequence. inferred from yeast one-hybrid assay Used when an annotation is based on the interaction of a protein with a DNA fragment in a yeast one-hybrid assay. The assay involves screening a library of candidate proteins for the ability bind to a target, cis-regulatory element or any other short, DNA binding sequence placed 5' to a yeast reporter gene. inferred from oligonucleotide microarray Mus musculus inferred from transgenic rescue inferred from yeast 2-hybrid assay Used when an annotation is based on the interaction between two proteins in a yeast two-hybrid assay. The assay involves screening a trap-tagged library with a bait-tagged vector. The library is tagged with a DNA-binding domain (trap) and the bait is tagged with a transcriptional activation domain. Interaction between a library-trap protein and the bait results in activation of a yeast reporter gene whose transcription can be experimentally assayed.