Bin Chen; Ying Ding; David Wild Bin Chen April, 2011 A web ontology for chemogenomics/systems chemical biology. Current version 1.0 is available at http://chem2bio2rdf.org/chem2bio2rdf.owl see details at http://chem2bio2owl.wikispaces.com structural similar compounds hasNeighbor The experimental results iSA Confidence in the containing instance. Usually a statistical measure. 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. Scientific evidence supporting the existence of the entity as described. 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'. Defines the chemical structure and other information about this molecule, using an instance of class chemicalStructure. Values of this property define external cross-references from this entity to entities in external databases. OBO_REL:0000012 relationship Note that adjacent_to as thus defined is not a symmetric relation, in contrast to its instance-level counterpart. For it can be the case that Cs are in general such as to be adjacent to instances of C1 while no analogous statement holds for C1s in general in relation to instances of C. Examples are: nuclear membrane adjacent_to cytoplasm; seminal vesicle adjacent_to urinary bladder; ovary adjacent_to parietal pelvic peritoneum adjacent_to OBO_REL:0000022 relationship agent_in OBO_REL:0000010 relationship Containment obtains in each case between material and immaterial continuants, for instance: lung contained_in thoracic cavity; bladder contained_in pelvic cavity. Hence containment is not a transitive relation. If c part_of c1 at t then we have also, by our definition and by the axioms of mereology applied to spatial regions, c located_in c1 at t. Thus, many examples of instance-level location relations for continuants are in fact cases of instance-level parthood. For material continuants location and parthood coincide. Containment is location not involving parthood, and arises only where some immaterial continuant is involved. To understand this relation, we first define overlap for continuants as follows: c1 overlap c2 at t =def for some c, c part_of c1 at t and c part_of c2 at t. The containment relation on the instance level can then be defined (see definition): contained_in OBO_REL:0000011 relationship contains OBO_REL:0000016 relationship derived_into OBO_REL:0000015 relationship Derivation as a relation between instances. The temporal relation of derivation is more complex. Transformation, on the instance level, is just the relation of identity: each adult is identical to some child existing at some earlier time. Derivation on the instance-level is a relation holding between non-identicals. More precisely, it holds between distinct material continuants when one succeeds the other across a temporal divide in such a way that at least a biologically significant portion of the matter of the earlier continuant is inherited by the later. Thus we will have axioms to the effect that from c derives_from c1 we can infer that c and c1 are not identical and that there is some instant of time t such that c1 exists only prior to and c only subsequent to t. We will also be able to infer that the spatial region occupied by c as it begins to exist at t overlaps with the spatial region occupied by c1 as it ceases to exist in the same instant. derives_from OBO_REL:0000021 relationship has_agent OBO_REL:0000024 relationship See reasons for obsoletion of improper_part_of has_improper_part OBO_REL:0000005 relationship has_integral_part OBO_REL:0000003 relationship has_part OBO_REL:0000007 relationship has_proper_part OBO_REL:0000025 relationship OBSOLETE. The definition is "As for part_of, with the additional constraint that subject and object may be identical". However, part_of is already reflexive, therefore improper_part_of is identical to part_of. If read differently, as "improper_part_of is part_of but not proper_part_of",improper_part_of becomes identity. So, improper_part_of is either identical to part_of or to identity, and not an intuitive synonym for either of them. [Robert Hoehndorf] improper_part_of OBO_REL:0000004 relationship integral_part_of OBO_REL:0000008 relationship Location as a relation between instances: The primitive instance-level relation c located_in r at t reflects the fact that each continuant is at any given time associated with exactly one spatial region, namely its exact location. Following we can use this relation to define a further instance-level location relation - not between a continuant and the region which it exactly occupies, but rather between one continuant and another. c is located in c1, in this sense, whenever the spatial region occupied by c is part_of the spatial region occupied by c1. Note that this relation comprehends both the relation of exact location between one continuant and another which obtains when r and r1 are identical (for example, when a portion of fluid exactly fills a cavity), as well as those sorts of inexact location relations which obtain, for example, between brain and head or between ovum and uterus located_in OBO_REL:0000009 relationship location_of OBO_REL:0000002 relationship Parthood as a relation between instances: The primitive instance-level relation p part_of p1 is illustrated in assertions such as: this instance of rhodopsin mediated phototransduction part_of this instance of visual perception. This relation satisfies at least the following standard axioms of mereology: reflexivity (for all p, p part_of p); anti-symmetry (for all p, p1, if p part_of p1 and p1 part_of p then p and p1 are identical); and transitivity (for all p, p1, p2, if p part_of p1 and p1 part_of p2, then p part_of p2). Analogous axioms hold also for parthood as a relation between spatial regions. For parthood as a relation between continuants, these axioms need to be modified to take account of the incorporation of a temporal argument. Thus for example the axiom of transitivity for continuants will assert that if c part_of c1 at t and c1 part_of c2 at t, then also c part_of c2 at t. Parthood as a relation between classes: To define part_of as a relation between classes we again need to distinguish the two cases of continuants and processes, even though the explicit reference to instants of time now falls away. For continuants, we have C part_of C1 if and only if any instance of C at any time is an instance-level part of some instance of C1 at that time, as for example in: cell nucleus part_ of cell. part_of OBO_REL:0000020 relationship participates_in OBO_REL:0000017 relationship An example is: translation preceded_by transcription; aging preceded_by development (not however death preceded_by aging). Where derives_from links classes of continuants, preceded_by links classes of processes. Clearly, however, these two relations are not independent of each other. Thus if cells of type C1 derive_from cells of type C, then any cell division involving an instance of C1 in a given lineage is preceded_by cellular processes involving an instance of C. The assertion P preceded_by P1 tells us something about Ps in general: that is, it tells us something about what happened earlier, given what we know about what happened later. Thus it does not provide information pointing in the opposite direction, concerning instances of P1 in general; that is, that each is such as to be succeeded by some instance of P. Note that an assertion to the effect that P preceded_by P1 is rather weak; it tells us little about the relations between the underlying instances in virtue of which the preceded_by relation obtains. Typically we will be interested in stronger relations, for example in the relation immediately_preceded_by, or in relations which combine preceded_by with a condition to the effect that the corresponding instances of P and P1 share participants, or that their participants are connected by relations of derivation, or (as a first step along the road to a treatment of causality) that the one process in some way affects (for example, initiates or regulates) the other. preceded_by OBO_REL:0000018 relationship precedes OBO_REL:0000006 relationship proper_part_of relationship this relation was superfluous, so it has been obsoleted relationship OBO_REL:0000013 relationship When an embryonic oenocyte (a type of insect cell) is transformed into a larval oenocyte, one and the same continuant entity preserves its identity while instantiating distinct classes at distinct times. The class-level relation transformation_of obtains between continuant classes C and C1 wherever each instance of the class C is such as to have existed at some earlier time as an instance of the distinct class C1 (see Figure 2 in paper). This relation is illustrated first of all at the molecular level of granularity by the relation between mature RNA and the pre-RNA from which it is processed, or between (UV-induced) thymine-dimer and thymine dinucleotide. At coarser levels of granularity it is illustrated by the transformations involved in the creation of red blood cells, for example, from reticulocyte to erythrocyte, and by processes of development, for example, from larva to pupa, or from (post-gastrular) embryo to fetus or from child to adult. It is also manifest in pathological transformations, for example, of normal colon into carcinomatous colon. In each such case, one and the same continuant entity instantiates distinct classes at different times in virtue of phenotypic changes. transformation_of OBO_REL:0000014 relationship Obsoleted transformed_into The abstract of a paper abstract The action type of drug drug interaction. refer to DCDB drug action type. Example: same target; metabolism actionType ADMET binding functional bioassy type assayType Chemical proteion interaction has biological interest. e.g, compound has positive results in bioassay(i.e, IC50<30um), compound is the subtrate of a reaction, etc. biologicalInterest drug brand name brandName categoriesOfEvidence description disorder classification, refer to OMIM example: metabolic, Bone, Cancer disorderClass whether the protein/gene is drug target. refer to DrugBank, TTD drugTarget approved biotech illicit investigational nutraceutical small molecule withdrawn drug type. Refer to DrugBank drugType include in vitro, in vivo, two-hybrid, etc. experimentType 166 MDL public keys fingerprint Gene Ontology ID gOID refer to HGNC gene family geneFamily it include small molecule, biotech, etc. group iSSN source id, either primary id of the original source or url identifier source name (e.g., DrugBank, PubChem, etc) identifierType indication journalName http://semanticscience.org/resource/CHEMINF_000251 The logarithm of octanol-water partition coefficient, which is the ratio of the molecules dissolved in octanol to those dissolved in pure un-ionized water upon mixture equilibration. This can be measured or predicted. The value is dimensionless. May depend on molecular conformation when computed The method to measure the outcome. Example: Ki, Kd, IC50, EC50 measurement mechanismOfAction number of atoms number of hydrogen acceptors number of hydrogen donors number of rotatable bonds organism pharmacal classification for drug drug interaction, refer to DCDB. Example: pharmacodynamical, pharmacokinetical pharmacalClassification pharmacology pubmed id pmid includes: >,>=,<=,<,=,~ relation synonym tissue outcome unit. example: um, nm unit value The authors of this publication, one per property value. Describes the availability of this data (e.g. a copyright statement). LEFT-TO-RIGHT RIGHT-TO-LEFT 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. 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. 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. ACTIVATION ACTIVATION-ALLOSTERIC ACTIVATION-NONALLOSTERIC INHIBITION INHIBITION-ALLOSTERIC INHIBITION-COMPETITIVE INHIBITION-IRREVERSIBLE INHIBITION-NONCOMPETITIVE INHIBITION-OTHER INHIBITION-UNCOMPETITIVE 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 the active site. INHIBITION-IRREVERSIBLE Irreversible inhibitors are compounds that irreversibly inhibit the specified enzyme activity by binding to the enzyme and dissociating so slowly that it is considered irreversible. For example, alkylating agents, such as iodoacetamide, irreversibly inhibit the catalytic activity of some enzymes by modifying cysteine side chains. INHIBITION-NONCOMPETITIVE Noncompetitive inhibitors are compounds that noncompetitively inhibit the specified enzyme by binding reversibly to both the free enzyme and to the enzyme-substrate complex. The inhibitor and substrate may be bound to the enzyme simultaneously and do not exclude each other. However, only the enzyme-substrate complex (not the enzyme-substrate-inhibitor complex) is catalytically active. INHIBITION-OTHER Compounds that inhibit the specified enzyme activity by a mechanism that has been characterized, but that cannot be clearly classified as irreversible, competitive, noncompetitive, uncompetitive, or allosteric. INHIBITION-UNCOMPETITIVE Uncompetitive inhibitors are compounds that uncompetitively inhibit the specified enzyme activity by binding reversibly to the enzyme-substrate complex but not to the enzyme alone. ACTIVATION-NONALLOSTERIC Nonallosteric activators increase the specified enzyme activity by means other than allosteric. ACTIVATION-ALLOSTERIC Allosteric activators increase the specified enzyme activity by binding reversibly to the enzyme and inducing a conformational change that increases the affinity of the enzyme to its substrates without affecting its VMAX. LEFT-TO-RIGHT REVERSIBLE RIGHT-TO-LEFT 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. The name of the external database to which this xref refers. 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. 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) 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) 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) 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. 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. The primary identifier in the external database of the object to which this xref refers. 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. This flag represents whether the binding feature is within the same molecule or not. 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) 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) Defines the molecular weight of the molecule, in daltons. 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. A measure of the concentration of magnesium (Mg) in solution. (pMg = -log₁₀[Mg²⁺]) The phenotype data from PATO, formatted as PhenoXML (defined at http://www.fruitfly.org/~cjm/obd/formats.html) 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) EQUAL GREATER-THAN LESS-THAN 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. 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. 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'. The source in which the reference was published, such as: a book title, or a journal title and volume and pages. Specifies whether a conversion occurs spontaneously or not. If the spontaneity is not known, the SPONTANEOUS property should be left empty. The preferred full name for this entity. LEFT-TO-RIGHT REVERSIBLE RIGHT-TO-LEFT 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. 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. 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. CML InChI SMILES InChi openeyeCanonicalSMILES openeyeISOSMILES openeye_can_smiles openeye_iso_smiles This property specifies which format is used to define chemical structure data. Temperature in Celsius FORWARD REVERSE The direction of the template reaction on the template. The external controlled vocabulary term. The title of the publication. The URL at which the publication can be found, if it is available through the Web. The value of the score. The year in which this publication was published. c2b2r:ADP-ribosylation Definition: The addition of a ADP-ribosyl group. ADP-ribosylation c2b2r:Abundance Definition: The abundance of a chemical (if chemical synthesis is not known). Example: CYP27B1 protein affects the abundance of Calcitriol c2b2r:Acetylation Definition: The addition of an acetyl group. Example: resveratrol results in decreased acetylation of TRP53 protein c2b2r:Activation GO:0051099 Definition: Any process that activates or increases the rate or extent of binding, the selective interaction of a molecule with one or more specific sites on another molecule. Synonym: positive regulation of binding; activation of binding c2b2r:Activity Definition: An elemental function of a molecule. Activity c2b2r:Acylation Definition: The addition of an acyl group. Acylation c2b2r:Alkylation Definition: The addition of an alkyl group. Alkylation c2b2r:Amination Definition: The addition of an amine group. c2b2r:Binding GO:0005488 Definition:The selective, often stoichiometric, interaction of a molecule with one or more specific sites on another molecule. Comments: In general, it describes the physical interaction between compound and gene (or gene expression products), it always has binding affinity values. Related Databases: BindingDB, ChEMBL, PubChem BioAssay, Kidb c2b2r:BioAssay Definition: A scientific experiment to measure the effects of some substance on target, cell, or a living organism Comments: refer to BioAssay Ontology project. Related Databases: PubChem BioAssay, ChEMBL Bioassay c2b2r:Carbamoylation Definition: The addition of a carbamoyl group. Carbamoylation c2b2r:Carboxylation Definition: The addition of a carboxyl group. Carboxylation c2b2r:ChemicalProteinInteraction Definition: a biological relationship between compound and protein (or associated entities (i.e., mRNA)). Comments: Related Databases: ChEMBL, BindingDB, DPSP Ki, TTD, BindingMOAD, DrugBank, CTD, MATADOR, ArrayExpress, KEGG c2b2r:ChemicalRegulatesProtein Definition: Small molecule regulates the function or property of protein (or associated entities (i.e., mRNA)) ChemicalRegulatesProtein c2b2r:ChemicalSynthesis Definition: A biochemical event resulting in a new chemical product. ChemicalSynthesis c2b2r:Cleavage Definition: The processing or splitting of a molecule, not necessarily leading to the destruction of the molecule. Cleavage c2b2r:Degradation Definition: Catabolism or breakdown. Degradation c2b2r:DirectActivityRegulation Definition: The process of regulation via direct physical interaction DirectActivityRegulation c2b2r:Disease Definition: any condition that causes pain, dysfunction, distress, social problems, and/or death to the person afflicted, or similar problems for those in contact with the person. Comments: refer to OMIM Synonyms: Disorder Related Databases: OMIM, CTD Disease, PharmGKB disease, Disease ontology c2b2r:DrugDrugInteraction Definition: A drug interaction is a situation in which a substance affects the activity of a drug, i.e. the effects are increased or decreased, or they produce a new effect that neither produces on its own.(from wiki) Comments: Also consider combinatorial drugs, which shows polypharmacology Instance examples: http://chem2bio2rdf.org/dcdb/resource/dcdb_drug_interaction/DI00001 Related Databases: DCDB, DrugBank c2b2r:DrugInducedSideEffect Definition: A drug interaction that results in side effect related databases: SIDER c2b2r:DrugTreament Definition: The use of drug to treat disease Related databases: Diseasome c2b2r:Entity Definition: A discrete unit involved in systems chemical biology/chemogenomics Rationale:It includes both continuants (physical entities, genes, disease) and occurents (interactions, pathways, side effects and bioassays). The definition of continuants and occurents are decribed in Basic Formal Ontology (BFO). c2b2r:Ethylation Definition: The addition of an ethyl group. Ethylation c2b2r:Export Definition: The movement of a molecule out of a cell (by more specific means than secretion). c2b2r:Expression GO:0010468 Definition: The process in which a gene's sequence is converted into a mature gene product or products (proteins or RNA). c2b2r:Farnesylation Definition: The addition of a farnesyl group Farnesylation c2b2r:Folding GO:0006457 The process of assisting in the covalent and noncovalent assembly of single chain polypeptides or multisubunit complexes into the correct tertiary structure. Definition: The bending and positioning of a molecule to achieve conformational integrity. Example: 1-Butanol affects the folding of GH1 protein. c2b2r:Geranoylation Definition: The addition of a geranoyl group. Geranoylation c2b2r:Glucuronidation Definition: The addition of a sugar group to form a glucuronide, typically part of an inactivating or detoxifying reaction. Glucuronidation c2b2r:Glutathionylation Definition: The addition of a glutathione group. Glutathionylation c2b2r:Glycation Definition: The non-enzymatic addition of a sugar. Glycation c2b2r:Glycosylation Definition: The addition of a sugar group. Glycosylation c2b2r:Hydrolysis Definition: The splitting of a molecule via the specific use of water. Hydrolysis c2b2r:Hydroxylation Definition: The addition of a hydroxy group. Hydroxylation c2b2r:Import Definition: The movement of a molecule into a cell (by more specific means than uptake). c2b2r:IndirectActivityRegulation Definition: The process of regulation via indirect interaction c2b2r:Inhibition GO:0051100 Definition: Any process that stops or reduces the rate or extent of binding, the selective interaction of a molecule with one or more specific sites on another molecule Synonym: negative regulation of binding; inhibition of binding c2b2r:Lipidation Definition: The addition of a lipid group. Lipidation c2b2r:Localization GO:0051179 Any process in which a cell, a substance, or a cellular entity, such as a protein complex or organelle, is transported to, and/or maintained in a specific location. Definition: Part of the cell where a molecule resides. Example: Cyclophosphamide affects the localization of HCRT protein. c2b2r:MacromoleculeMetabolicProcess GO:0043170 The chemical reactions and pathways involving macromolecules, any molecule of high relative molecular mass, the structure of which essentially comprises the multiple repetition of units derived, actually or conceptually, from molecules of low relative molecular mass Definition: The biochemical alteration of a molecule's structure (does not include changes in expression, stability, folding, localization, splicing). c2b2r:Methylation Definition: The addition of a methyl group. Methylation c2b2r:Mutagenesis GO:0006280 Definition: The genetic alteration of a gene product. Example: Acrylamide results in increased mutagenesis of HPRT1 gene Comment: This term was made obsolete in GO because mutagenesis is not a valid biological process in which gene products would normally participate. c2b2r:Myristoylation Definition: The addition of a myristoyl group. Myristoylation c2b2r:N-linkedGlycosylation Definition: The addition of a sugar group to an amide nitrogen. N-linkedGlycosylation c2b2r:NegativeRegulationOfExpression GO:0010629 Definition: The process that decreases the frequency, rate or extent of gene expression. Example: 2-nitropropane results in decreased expression of PGCP mRNA c2b2r:Nitrosation Definition: The addition of a nitroso or nitrosyl group. Nitrosation c2b2r:Nucleotidylation Definition: The addition of a nucleotidyl group. Nucleotidylation c2b2r:O-linkedGlycosylation Definition: The addition of a sugar group to a hydroxyl group. O-linkedGlycosylation c2b2r:Outcome Definition: the output of bioassay experiment Outcome c2b2r:Oxidation Definition: the loss of electrons Oxidation c2b2r:Palmitoylation Definition: The addition of a palmitoyl group. Palmitoylation c2b2r:Phosphorylation Definition: The addition of a phosphate group. Phosphorylation c2b2r:PhysicalProperty Definition: Physical property of small molecule PhysicalProperty c2b2r:PositiveRegulationOfExpression GO:0010628 Definition: The process that increases the frequency, rate or extent of gene expression. Example: 2,2-bis(4-hydroxyphenyl)-1,1,1-trichloroethane results in increased expression of ESR2 mRNA. c2b2r:Prenylation Definition: The addition of a prenyl group. Prenylation c2b2r:ProteinProteinInteraction Definition: two or more proteins bind together, often to carry out their biological function Comments: consider protein protein or protein DNA interaction. Cover yeast 2-hybrid data Instance examples: Related Databases: HPRD, DIP, BIOGRID c2b2r:ProteinRegulatesChemical Definition: protein regulates the function or property of small molecule. ProteinRegulatesChemical c2b2r:ReceptorAgonistActivity GO:0048018 Definition: Interacts with receptors such that the proportion of receptors in the active form is increased. Example: Calcitriol binds to and results in increased activity of VDR protein. c2b2r:ReceptorAntagonistActivity GO:0048019 Definition: Interacts with receptors to reduce the action of another ligand. c2b2r:Reduction Definition: The gain of electrons. Reduction c2b2r:Ribosylation Definition: The addition of a ribosyl group. Ribosylation c2b2r:Secretion Definition: The movement of a molecule out of a cell (by less specific means than export). c2b2r:SideEffect Definition: undesired effect from a medicine Comments: refer to SIDER, it does not need to be harmful. Synonyms: AdverseEffect, DrugAdverseReaction Related Databases: SIDER Popular Identifiers: umls_id c2b2r:SmallMoleculeMetabolicProcess GO:0044281 Definition: The chemical reactions involving small molecules, any monomeric molecule of small relative molecular mass Synonym: Reaction c2b2r:Splicing GO:0006371 Definition: The removal of introns to generate mRNA. Example: Fluorouracil affects the splicing of GAPDH mRNA. Comment: This term was made obsoletein GO because it represents several different processes. c2b2r:Stability Definition: Overall molecular integrity. Example: Pentobarbital results in decreased stability of GSTD2 mRNA. c2b2r:Sulfation Definition: The addition of a sulfate group. Sulfation c2b2r:Sumoylation Definition: The addition of a SUMO group. Sumoylation c2b2r:Transport Definition: The movement of a molecule into or out of a cell. c2b2r:Ubiquitination Definition: The addition of an ubiquitin group. Ubiquitination c2b2r:Uptake Definition: The movement of a molecule into a cell (by less specific means than import). bp:CellVocabulary 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 bp:CellularLocationVocabulary 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 1 1 bp:ChemicalStructure 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)'. bp:Complex 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) and the Stoichiometry of the components are known. 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 possible, elements of the cell such a mitochondria 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. bp:ControlledVocabulary Used to reference terms from external controlled vocabularies (CVs) from the ontology. To support consistency and compatibility, open, freely available CVs should be used whenever possible, such as the Gene Ontology (GO)15 or other open biological CVs listed on the OBO website (http://obo.sourceforge.net/). See the section on controlled vocabularies in Section 4 for more information. bp:Dna 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. bp:DnaRegion 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: Protein encoding region, promoter bp:EntityReferenceTypeVocabulary Definiiton: A reference to a term from an entity reference group ontology. As of the writing of this documentation, there is no standard ontology of these terms, though a common type is ‘homology’. bp:Evidence Definition: The support for a particular assertion, such as the existence of an interaction or pathway. Usage: At least one of confidence, evidenceCode, or experimentalForm 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. bp:EvidenceCodeVocabulary 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/ bp:ExperimentalFormVocabulary 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 bp:Gene Definition: A continuant that encodes information that can be inherited through replication. Rationale: Gene is an abstract continuant that can be best described as a "schema", a common conception commonly used by biologists to demark a component within genome. In BioPAX, Gene is considered a generalization over eukaryotic and prokaryotic genes and is used only in genetic interactions. Gene is often confused with DNA and RNA fragments, however, these are considered the physical encoding of a gene. N.B. Gene expression regulation makes use of DNA and RNA physical entities and not this class. Usage: Gene should only be used for describing GeneticInteractions. bp:Interaction 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. 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 bp:InteractionVocabulary 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 bp:Pathway 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 also soverlap, i.e. a single interaction might belong to multiple pathways. Pathways can also contain sub-pathways. Pathways are continuants. Synonyms: network, module, cascade, Examples: glycolysis, valine biosynthesis, EGFR signaling Instance examples: http://chem2bio2rdf.org/kegg/resource/kegg_pathway/hsa00052 Related Databases: KEGG, Reactome Popular Identifiers: KEGG ID bp:PhenotypeVocabulary 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. bp:PhysicalEntity Definition: A pool of molecules or molecular complexes. Comments: Each PhysicalEntity is defined by a sequence or structure based on an EntityReference AND any set of Features that are given. For example, ser46 phosphorylated p53 is a physical entity in BioPAX defined by the p53 sequence and the phosphorylation feature on the serine at position 46 in the sequence. 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 unknowns or unneccesary. Features that are known to not be on the molecules should be explicitly stated with the "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 bp:Protein 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. bp:Provenance Definition: The direct source of 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, tool or algorithm. The xref property may contain a publicationXref referencing a publication describing the data source (e.g. a database publication). A unificationXref may be used when pointing to an entry in a database of databases describing this database. Examples: A database, scoring method or person name. bp:PublicationXref 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 bp:RelationshipTypeVocabulary 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 bp:RelationshipXref 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. bp:Rna 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. bp:RnaRegion 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 1 bp:Score 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". bp:SequenceModificationVocabulary 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. bp:SequenceRegionVocabulary 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 bp:SmallMolecule Definition: A small bioactive molecule. Small is not precisely defined, but includes all metabolites and most drugs and does not include large polymers, including complex carbohydrates. Comment: Recently, a number of small molecule databases have become available to cross-reference from this class. Examples: glucose, penicillin, phosphatidylinositol Note: Complex carbohydrates are not currently modeled in BioPAX or most pathway databases, due to the lack of a publicly available complex carbohydrate database. Synonyms: Compound, Chemical, Drug related databases: PubChem, ChEBI, DrugBank bp:TissueVocabulary 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 1 1 bp:UnificationXref 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 may 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.. bp:UtilityClass Definition: This is a placeholder for classes, used for annotating the "Entity" and its subclasses. Mostly, these 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. bp:Xref 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. Bin Chen; Ying Ding; David Wild Bin Chen April, 2011 A web ontology for chemogenomics/systems chemical biology. Current version 1.0 is available at http://chem2bio2rdf.org/chem2bio2rdf.owl see details at http://chem2bio2owl.wikispaces.com OBO_REL:0000019 relationship Has_participant is a primitive instance-level relation between a process, a continuant, and a time at which the continuant participates in some way in the process. The relation obtains, for example, when this particular process of oxygen exchange across this particular alveolar membrane has_participant this particular sample of hemoglobin at this particular time. has_participant