]> EDDA Study Designs 49 Aug 17, 2015 10:07:29 AM Authors: Richard D. Boyce, PhD*, Carol Collins**, John Horn**, Ira Kalet**, John Gennari**. *University of Pittsburgh Department of Biomedical Informatics **All authors are currently with the University of Washington. This project is supported by a grant from the National Library of Medicine: "Addressing gaps in clinically useful evidence on drug-drug interactions" (1R01LM011838-01) Revisions to the DIKB evidence taxonomy The Drug Interaction Knowledge Base ontology. This version is reorganizes the evidence taxonomy for retrospective studies to more properly distinguish various observational studies. It also integrates type from EDDA (http://bioportal.bioontology.org/ontologies/EDDA) This is version 1.0 of the BioPAX Level 3 ontology. The goal of the BioPAX group is to develop a common exchange format for biological pathway data. More information is available at http://www.biopax.org. This ontology is freely available under the LGPL (http://www.gnu.org/copyleft/lesser.html). This ontology was generated from an ontology revision in WebProtege http://webprotege.stanford.edu Version 1.6 boycer system wenzhang Tanja Bekhuis Eugene Tseytlin Micropublications: a Semantic Model for Claims, Evidence, Arguments and Annotations in Biomedical Communications. Author: Tim Clark (1,2,3) Contributors: Paolo Ciccarese (1,2), Carole Goble (3) Version 1.16, September 12, 2013. (1) Massachusetts General Hospital, Dept. of Neurology (2) Harvard Medical School (3) University of Manchester, School of Computer Science EDDA Study Designs and Publications OWL file 1.3 1.16 Comparative Effectiveness Research (CER) Design Terminology, NLM Medical Subject Headings (MeSH), Emtree, National Cancer Institute Thesaurus (NCIT) Terminology of study designs and publication types (beta version). Developed by the Evidence in Documents, Discovery, and Analysis (EDDA) Group. Tanja Bekhuis (PI); Eugene Tseytlin (Systems Developer); Ashleigh Faith (Taxonomist). Department of Biomedical Informatics, University of Pittsburgh School of Medicine, Pennsylvania, US. This work was made possible by the US National Library of Medicine, National Institutes of Health, grant no. R00LM010943. Based on research described in Bekhuis T, Demner-Fushman D, Crowley RS. Comparative effectiveness research designs: an analysis of terms and coverage in Medical Subject Headings (MeSH) and Emtree. Journal of the Medical Library Association (JMLA). 2013 April;101(2):92-100. PMC3634392. The terminology appearing in JMLA has been enriched with terms from MeSH, NCI Thesaurus (NCIT), and Emtree, the controlled vocabularies for MEDLINE, the National Cancer Institute, and Embase, respectively, as well as from published research literature. Variants include synonyms for preferred terms, singular and plural forms, and American and British spellings. Definitions, if they exist, are mainly from MeSH, NCIT, Emtree, and medical dictionaries. A class for Publication Type is included because investigators consider type and design when screening reports for inclusion in comparative effectiveness research. Ashleigh Faith 1.15 National Center for Biomedical Ontology (NCBO) BioPortal Contributor An entity responsible for making contributions to the content of the resource. Examples of a Contributor include a person, an organisation, or a service. Typically, the name of a Contributor should be used to indicate the entity. Creator An entity primarily responsible for making the content of the resource. Examples of a Creator include a person, an organisation, or a service. Typically, the name of a Creator should be used to indicate the entity. Date A date associated with an event in the life cycle of the resource. Typically, Date will be associated with the creation or availability of the resource. Recommended best practice for encoding the date value is defined in a profile of ISO 8601 [W3CDTF] and follows the YYYY-MM-DD format. Description An account of the content of the resource. Description may include but is not limited to: an abstract, table of contents, reference to a graphical representation of content or a free-text account of the content. Format The physical or digital manifestation of the resource. Typically, Format may include the media-type or dimensions of the resource. Format may be used to determine the software, hardware or other equipment needed to display or operate the resource. Examples of dimensions include size and duration. Recommended best practice is to select a value from a controlled vocabulary (for example, the list of Internet Media Types [MIME] defining computer media formats). Publisher An entity responsible for making the resource available Examples of a Publisher include a person, an organisation, or a service. Typically, the name of a Publisher should be used to indicate the entity. Source A reference to a resource from which the present resource is derived. The present resource may be derived from the Source resource in whole or in part. Recommended best practice is to reference the resource by means of a string or number conforming to a formal identification system. Title Typically, a Title will be a name by which the resource is formally known. A name given to the resource. Absolute location as defined by the referenced sequence database record. E.g. an operon has a absolute region on the DNA molecule referenced by the UnificationXref. A binding feature represents a "half" of the bond between two entities. This property points to another binding feature which represents the other half. The bond can be covalent or non-covalent. A cell type, e.g. 'HeLa'. This should reference a term in a controlled vocabulary of cell types. Best practice is to refer to OBO Cell Ontology. http://www.obofoundry.org/cgi-bin/detail.cgi?id=cell A cellular location, e.g. 'cytoplasm'. This should reference a term in the Gene Ontology Cellular Component ontology. The location referred to by this property should be as specific as is known. If an interaction is known to occur in multiple locations, separate interactions (and physicalEntities) must be created for each different location. If the location of a participant in a complex is unspecified, it may be assumed to be the same location as that of the complex. A molecule in two different cellular locations are considered two different physical entities. Any cofactor(s) or coenzyme(s) required for catalysis of the conversion by the enzyme. COFACTOR is a sub-property of PARTICIPANTS. Any cofactor(s) or coenzyme(s) required for catalysis of the conversion by the enzyme. This is a suproperty of participants. The stoichiometry of components in a complex Confidence in the containing instance. Usually a statistical measure. The entity that is controlled, e.g., in a biochemical reaction, the reaction is controlled by an enzyme. CONTROLLED is a sub-property of PARTICIPANTS. The entity that is controlled, e.g., in a biochemical reaction, the reaction is controlled by an enzyme. Controlled is a sub-property of participants. The controlling entity, e.g., in a biochemical reaction, an enzyme is the controlling entity of the reaction. CONTROLLER is a sub-property of PARTICIPANTS. 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. For biochemical reactions, this property refers to the standard transformed Gibbs energy change for a reaction written in terms of biochemical reactants (sums of species), delta-G Since Delta-G can change based on multiple factors including ionic strength and temperature a reaction can have multiple DeltaG values. Variable features that are observed for the entities of this entityReference - such as known PTM or methylation sites and non-covalent bonds. Note that this is an aggregate list of all known features and it does not represent a state itself. Variable features that are observed for this entity - such as known PTM or methylation sites and non-covalent bonds. Reference entity for this physical entity. A controlled vocabulary term that is used to describe the type of grouping such as homology or functional group. 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'. A feature of the experimental form of the participant of the interaction, such as a protein tag. It is not expected to occur in vivo or be necessary for the interaction. The experimental forms associated with an evidence instance. Descriptor of this experimental form from a controlled vocabulary. The gene or physical entity that this experimental form describes. Sequence features of the owner physical entity. Location of the feature on the sequence of the interactor. For modification features this is the modified base or residue. For binding features this is the binding site and for fragment features this is the location of the fragment on the "base" sequence. One feature may have more than one location, used e.g. for features which involve sequence positions close in the folded, three-dimensional state of a protein, but non-continuous along the sequence. Small Molecules can have binding features but currently it is not possible to define the binding site on the small molecules. In those cases this property should not be specified. Location of the feature on the sequence of the interactor. One feature may have more than one location, used e.g. for features which involve sequence positions close in the folded, three-dimensional state of a protein, but non-continuous along the sequence. A controlled vocabulary term describing the type of the sequence location of the feature such as C-Terminal or SH2 Domain. A controlled vocabulary term describing the type of the sequence location such as C-Terminal or SH2 Domain. The score of an interaction e.g. a genetic interaction score. Controlled vocabulary annotating the interaction type for example, "phosphorylation reaction". This annotation is meant to be human readable and may not be suitable for computing tasks, like reasoning, that require formal vocabulary systems. For instance, this information would be useful for display on a web page or for querying a database. The PSI-MI interaction type controlled vocabulary should be used. This is browsable at: http://www.ebi.ac.uk/ontology-lookup/browse.do?ontName=MI&termId=MI%3A0190&termName=interaction%20type External controlled vocabulary annotating the interaction type, for example "phosphorylation". This is annotation useful for e.g. display on a web page or database searching, but may not be suitable for other computing tasks, like reasoning. This quantity is dimensionless and is usually a single number. The measured equilibrium constant for a biochemical reaction, encoded by the slot KEQ, is actually the apparent equilibrium constant, K'. Concentrations in the equilibrium constant equation refer to the total concentrations of all forms of particular biochemical reactants. For example, in the equilibrium constant equation for the biochemical reaction in which ATP is hydrolyzed to ADP and inorganic phosphate: K' = [ADP][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) The participants on the left side of the conversion interaction. Since conversion interactions may proceed in either the left-to-right or right-to-left direction, occupants of the LEFT property may be either reactants or products. LEFT is a sub-property of PARTICIPANTS. The participants on the left side of the conversion interaction. Since conversion interactions may proceed in either the left-to-right or right-to-left direction, occupants of the left property may be either reactants or products. left is a sub-property of participants. An entity reference that qualifies for the definition of this group. For example a member of a PFAM protein family. An entity feature that belongs to this homology grouping. Example: a homologous phosphorylation site across a protein family. An entity feature that belongs to this homology grouping. These features should be of the same class of this EntityFeature These features should be an EntityFeature of an EntityReference which is a memberEntityReference of the EntityReference of this feature. If this set is not empty than the sequenceLocation of this feature should be non-specified. Example: a homologous phosphorylation site across a protein family. This property stores the members of a generic physical entity. For representing homology generics a better way is to use generic entity references and generic features. However not all generic logic can be captured by this, such as complex generics or rare cases where feature cardinality is variable. Usages of this property should be limited to such cases. Description and classification of the feature. The next step(s) of the pathway. Contains zero or more pathwayStep instances. If there is no next step, this property is empty. Multiple pathwayStep instances indicate pathway branching. Sequence features where the owner physical entity has a feature. If not specified, other potential features are not known. An organism, e.g. 'Homo sapiens'. This is the organism that the entity is found in. Pathways may not have an organism associated with them, for instance, reference pathways from KEGG. Sequence-based entities (DNA, protein, RNA) may contain an xref to a sequence database that contains organism information, in which case the information should be consistent with the value for ORGANISM. This property lists the entities that participate in this interaction. For example, in a biochemical reaction, the participants are the union of the reactants and the products of the reaction. This property has a number of sub-properties, such as LEFT and RIGHT used in the biochemicalInteraction class. Any participant listed in a sub-property will automatically be assumed to also be in PARTICIPANTS by a number of software systems, including Protege, so this property should not contain any instances if there are instances contained in a sub-property. Stoichiometry of the left and right participants. The set of interactions and/or pathwaySteps in this pathway/network. Each instance of the pathwayStep class defines: 1) a set of interactions that together define a particular step in the pathway, for example a catalysis instance and the conversion that it catalyzes; 2) an order relationship to one or more other pathway steps (via the NEXT-STEP property). Note: This ordering is not necessarily temporal - the order described may simply represent connectivity between adjacent steps. Temporal ordering information should only be inferred from the direction of each interaction. The ordering of components (interactions and pathways) in the context of this pathway. This is useful to specific circular or branched pathways or orderings when component biochemical reactions are normally reversible, but are directed in the context of this pathway. The phenotype quality used to define this genetic interaction e.g. viability. The physical entity to be annotated with stoichiometry. The product of a template reaction. Definition:A controlled vocabulary term that defines the type of relationship that this xref defines. Usage: There is currently no controlled vocabulary of relationship types for BioPAX, although one will be created in the future as the usage of this property increases. The participants on the right side of the conversion interaction. Since conversion interactions may proceed in either the left-to-right or right-to-left direction, occupants of the RIGHT property may be either reactants or products. RIGHT is a sub-property of PARTICIPANTS. This property defines the source of the scoring methodology -- a publication or web site describing the scoring methodology and the range of values. The begin position of a sequence interval. The end position of a sequence interval. The central process that take place at this step of the biochemical pathway. An interaction or a pathway that are a part of this pathway step. Defines the chemical structure and other information about this molecule, using an instance of class chemicalStructure. The sub region of a region or nucleic acid molecule. The sub region must be wholly part of the region, not outside of it. The template molecule that is used in this template reaction. An external controlled vocabulary of tissue types. Values of this property define external cross-references from this entity to entities in external databases. The authors of this publication, one per property value. Describes the availability of this data (e.g. a copyright statement). 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. 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. For example E.Coli's lac operon ensures that lacZ gene is only synthesized when there is enough lactose in the medium. 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. LEFT-TO-RIGHT RIGHT-TO-LEFT 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. 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. 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. ACTIVATION ACTIVATION-ALLOSTERIC ACTIVATION-NONALLOSTERIC INHIBITION INHIBITION-ALLOSTERIC INHIBITION-COMPETITIVE INHIBITION-IRREVERSIBLE INHIBITION-NONCOMPETITIVE INHIBITION-OTHER INHIBITION-UNCOMPETITIVE 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. This property represents the direction of the reaction. If a reaction will run in a single direction under all biological contexts then it is considered irreversible and has a direction. Otherwise it is reversible. LEFT-TO-RIGHT REVERSIBLE RIGHT-TO-LEFT 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). 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. 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. Warning: Subproperties of name are functional, that is we expect to have only one standardName and shortName for a given entity. If a user decides to assign a different name to standardName or shortName, they have to remove the old triplet from the model too. If the old name should be retained as a synonym a regular "name" property should also be introduced with the old name. 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. This flag represents whether the binding feature is within the same molecule or not. A true value implies that the entityReferences of this feature and its binding partner are the same. 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 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. Synonyms for this entity. standardName and shortName are subproperties of this property and if declared they are automatically considered as names. Warning: Subproperties of name are functional, that is we expect to have only one standardName and shortName for a given entity. If a user decides to assign a different name to standardName or shortName, they have to remove the old triplet from the model too. If the old name should be retained as a synonym a regular "name" property should also be introduced with the old name. 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) 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. EQUAL GREATER-THAN LESS-THAN 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, if exists assigned by a standard nomenclature organization such as HUGO Gene Nomenclature Committee. Warning: Subproperties of name are functional, that is we expect to have only one standardName and shortName for a given entity. If a user decides to assign a different name to standardName or shortName, they have to remove the old triplet from the model too. If the old name should be retained as a synonym a regular "name" property should also be introduced with the old name. The preferred full name for this entity. 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. LEFT-TO-RIGHT REVERSIBLE RIGHT-TO-LEFT 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. This property holds a string of data defining chemical structure,in one of the three formats:<a href ="www.xml-cml.org">CML</a>, <a href = "www.daylight.com/dayhtml/smiles/">SMILES</a> or <a href="http://www.iupac.org/inchi/">InChI</a>. 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. This property specifies which format is used to define chemical structure data. CML InChI SMILES Temperature in Celsius The direction of the template reaction on the template. FORWARD REVERSE 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 value of the score. This can be a numerical or categorical value. The year in which this publication was published. conference paper Tanja Bekhuis January 7, 2015 conference report Publication Type PT Describes the type of material the article represents (e.g., Review, Clinical Trial, Retracted Publication, Letter); see the PubMed Publication Types, e.g., review[pt]. Publication Types are arranged hierarchically with more specific terms arranged beneath broader terms. [http://www.ncbi.nlm.nih.gov/books/NBK3827/#pubmedhelp.Publication_Type_PT, August 2014] Tanja Bekhuis single blind design single blind trials single blind studies single blind method single blind methods single blind study single blind designs single blind trial Study Design C0035171 Study Type A plan detailing how a study will be performed in order to represent the phenomenon under examination, to answer the research questions that have been asked, and defining the methods of data analysis. Study design is driven by research hypothesis being posed, study subject/population/sample available, logistics/resources: technology, support, networking, collaborative support, etc. Describes the role the study plays in determining the interventions a subject receives. [NCIT_14.05d] [Contributing_Source_CDISC] Tanja Bekhuis Research Design Research Activity STYPE C15320 abstract Tanja Bekhuis summary abstract reports Intellectual Product abstract report Abstract Document synopses C60765 C0600678 synopsis summaries A written summary of the important points of a scientific article. [NCIT_14.08d] abstracts adaptive design adaptive designs adaptive studies adaptive study adaptive trial adaptive trials Research Activity C98704 ADAPT A study design which includes a prospectively planned opportunity for modification of one or more specified aspects of the study design and/or hypotheses based on analysis of data, usually interim data. [NCIT_14.05d] [Contributing_Source_CDISC] Ashleigh Faith C3274373 address addresses Manufactured Object C0376649 A formal speech or report. [NCIT_14.08d] C86945 Tanja Bekhuis analytical design Ashleigh Faith analytic design analytic designs analytic research analytic studies analytic study analytic trial analytic trials analytical designs analytical research analytical studies analytical study analytical trial analytical trials animal study animal experiments C93130 animal studies C0683949 A laboratory experiment using animals to study the development and progression of diseases. Animal studies also test how safe and effective new treatments are before they are tested in people. [NCIT_14.08d] Research Activity Tanja Bekhuis animal experiment article Tanja Bekhuis C1706852 November 13, 2014 Nonfictional prose forming an independent part of a publication. [NCIT_14.10d] [Contributing_Source_FDA] C47902 articles Intellectual Product before-after design before-after designs before-after studies before-after study before-after trial before-after trials before-and-after design before-and-after designs before-and-after studies before-and-after study before-and-after trial before-and-after trials bibliography resource guide Intellectual Product Resource Guides Ashleigh Faith A work consisting of a list of books, articles, documents, publications, and other items, usually on a single subject or related subjects. [MeSH_2014] Manufactured Object D016417 bibliographies biobibliography Tanja Bekhuis A bibliography containing biographical information about the author(s). [Oxford Dictionaries. Oxford University Press. http://www.oxforddictionaries.com/us/definition/american_english/biobibliography] April 15, 2015 biobibliographies biography obituaries Ashleigh Faith obituary Intellectual Product Autobiography autobiographies Works consisting of an account of the events, works, and achievements, personal and professional, during a person's life. It includes articles on the activities and accomplishments of living persons as well as the presentation of an obituary.[MeSH_2014] D019215 biographies biosurveillance population surveillance D055877 Tanja Bekhuis Health Care Activity Monitoring of information sources of potential value in detecting an emerging epidemic, whether naturally occurring or the result of bioterrorism. [MeSH_2014] case control design D016022 Research Activity case control designs case control studies case control study case control trial case control trials case-comparison studies case-compeer studies case-control design case-control designs case-control studies case-control study case-control trial case-control trials case-referent studies case-referrent study control study, case C0007328 case-base design case base study case base studies case base designs C15197 case base design case-base study Ashleigh Faith Studies which start with the identification of persons with a disease of interest and a control (comparison, referent) group without the disease. The relationship of an attribute to the disease is examined by comparing diseased and non-diseased persons with regard to the frequency or levels of the attribute in each group. [MeSH_2014] case-base designs case-base studies A study that compares two groups of people: those with the disease or condition under study (cases) and a very similar group of people who do not have the disease or condition (controls). Researchers study the medical and lifestyle histories of the people in each group to learn what factors may be associated with the disease or condition. For example, one group may have been exposed to a particular substance that the other was not. [NCIT_14.05d] case study case designs case studies case study case trial case trials case reports Ashleigh Faith Intellectual Product Used for original items reporting clinical work on not more than 4 individual cases. [Emtree_2014] case report case design C15362 C0085973 An uncontrolled observational study containing a detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NCIT_14.05d] A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [Case study | NCIT_14.05d] A study that identifies and samples individuals with a particular disease or condition, noting characteristics of the disease or condition and persons afflicted. Case studies are often used to call attention to new diseases or to diseases entering new populations. [Emtree_2014] [Dorland's Medical Dictionary_2011] Clinical presentations that may be followed by evaluative studies that eventually lead to a diagnosis. [Case report | MeSH_2014] D002363 case histories case history Research Activity case series Ashleigh Faith case series design case series designs case series studies case series study case series trial case series trials large case series C0150093 Research Activity A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NCIT_14.05d] C16229 a study that identifies and samples individuals with a particular disease or condition, noting characteristics of the disease or condition and persons afflicted. Case studies are often used to call attention to new diseases or to diseases entering new populations. [Case study | Emtree_2014] [Dorland's Medical Dictionary_2011] clinical audit Clinical governance Ashleigh Faith Health Care Activity A detailed review and evaluation of selected clinical records by qualified professional personnel to improve the quality of patient care and outcomes. The clinical audit was formally introduced in 1993 into the United Kingdom's National Health Service. [MeSH_2014] D054869 clinical trial trial, clinical Clinical Trial Generic clinical trial Clinical Trial C71104 A type of research study that tests how well new medical approaches work in people. These studies test new methods of screening, prevention, diagnosis, or treatment of a disease. [NCIT_14.05d] Research Activity Clinical Trials A research study that prospectively assigns human participants or groups of humans to one or more health-related interventions to evaluate the effects on health outcomes. [NCIT_14.05d] C0008976 Ashleigh Faith Clinical Trials, Unspecified closed cohort study closed cohort studies cohort studies, closed cohort study, closed studies, closed cohort study, closed cohort cluster quasi randomized controlled design Cluster non-randomized controlled design cluster quasi randomised controlled design cluster quasi randomised controlled designs cluster quasi randomised controlled studies cluster quasi randomised controlled study cluster quasi randomised controlled trial cluster quasi randomised controlled trials cluster quasi randomized controlled designs cluster quasi randomized controlled studies cluster quasi randomized controlled study cluster quasi randomized controlled trial cluster quasi randomized controlled trials cluster quasi-randomised controlled design cluster quasi-randomised controlled designs cluster quasi-randomised controlled studies cluster quasi-randomised controlled study cluster quasi-randomised controlled trial cluster quasi-randomised controlled trials cluster quasi-randomized controlled design cluster quasi-randomized controlled designs cluster quasi-randomized controlled studies cluster quasi-randomized controlled study cluster quasi-randomized controlled trial cluster quasi-randomized controlled trials Ashleigh Faith cluster randomized controlled design cluster randomised controlled design cluster randomised controlled designs cluster randomised controlled studies cluster randomised controlled study cluster randomised controlled trial cluster randomised controlled trials cluster randomized controlled designs cluster randomized controlled studies cluster randomized controlled study cluster randomized controlled trial cluster randomized controlled trials cluster randomized design cluster randomised design cluster randomised designs cluster randomised studies cluster randomised study cluster randomised trial cluster randomised trials cluster randomized designs cluster randomized studies cluster randomized study cluster randomized trial cluster randomized trials cohort before-after design cohort before-after design cohort before-after designs cohort before-after studies cohort before-after study cohort before-after trial cohort before-after trials cohort before-and-after design cohort before-and-after designs cohort before-and-after studies cohort before-and-after study cohort before-and-after trial cohort before-and-after trials cohort study Ashleigh Faith D015331 Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics. [Cohort studies | MeSH_2014] cohort design cohort designs cohort studies cohort trial cohort trials C15208 A research study that compares a particular outcome (such as lung cancer) in groups of individuals who are alike in many ways but differ by a certain characteristic (for example, female nurses who smoke compared with those who do not smoke). [NCIT_14.05d] C0009247 analysis, cohort cohort analysis Research Activity comment comments C0947611 Viewpoint note notes Intellectual Product editorial comments Remark commentary A written explanation, observation or criticism added to textual material. [NCIT_14.05d] [Contributing_Source_BRIDG] D016420 viewpoints Editorial Comment Ashleigh Faith; Tanja Bekhuis Remarks Work consisting of a critical or explanatory note written to discuss, support, or dispute an article or other presentation previously published. It may take the form of an article, letter, editorial, etc. It appears in publications under a variety of names: comment, commentary, editorial comment, viewpoint, etc. [MeSH_2014] commentaries C25393 April 14, 2015 note = note, discussion or commentary [Emtree Scope Note, April 14, 2015] community trial community design community designs community studies community study community trials The Community Trial is a planned experiment that involves administering an exposure within a community in order to elucidate its impact on the incidence of a specific disease in that community. The community trial is a choice when exposure cannot be prevented among control group. [NCIT_14.05d] C39365 Research Activity Ashleigh Faith C1516736 comparative study comparative design comparative designs comparative studies comparative trial comparative trials Comparison of outcomes, results, responses, etc for different techniques, therapeutic approaches or other inputs. [Comparitive study | MeSH_2014] Research Activity Ashleigh Faith D003160 Intellectual Product concurrent design concurrent designs concurrent studies concurrent study concurrent trial concurrent trials studies, concurrent conference proceedings Tanja Bekhuis Intellectual Product Conferences and Proceedings D003226 Manufactured Object consecutive case series C2985408 C93041 A clinical study that includes all eligible patients identified by the researchers during the study registration period. The patients are treated in the order in which they are identified. This type of study usually does not have a control group. [NCIT_14.08d] Research Activity Tanja Bekhuis controlled before-after design controlled before-after designs controlled before-after studies controlled before-after study controlled before-after trial controlled before-after trials controlled before-and-after design controlled before-and-after designs controlled before-and-after studies controlled before-and-after study controlled before-and-after trial controlled before-and-after trials D065187 Quantitative Concept Tanja Bekhuis November 7, 2014 A study in which observations are made before and after an intervention, both in a group that receives the intervention and in a control group that does not. [Controlled Before-After Studies | MeSH_2015] Research Activity controlled clinical trial Work consisting of a clinical trial involving one or more test treatments, at least one control treatment, specified outcome measures for evaluating the studied intervention, and a bias-free method for assigning patients to the test treatment. The treatment may be drugs, devices, or procedures studied for diagnostic, therapeutic, or prophylactic effectiveness. Control measures include placebos, active medicine, no-treatment, dosage forms and regimens, historical comparisons, etc. [MeSH_2014] clinical trial, controlled controlled clinical design controlled clinical designs controlled clinical studies controlled clinical study controlled clinical trials Ashleigh Faith Research Activity Therapeutic or Preventive Procedure D018848 Intellectual Product controlled cohort before-after design controlled cohort before-after design controlled cohort before-after designs controlled cohort before-after studies controlled cohort before-after study controlled cohort before-after trial controlled cohort before-after trials controlled cohort before-and-after design controlled cohort before-and-after designs controlled cohort before-and-after studies controlled cohort before-and-after study controlled cohort before-and-after trial controlled cohort before-and-after trials controlled design controlled designs controlled studies controlled study controlled trial controlled trials C28279 C0681867 Ashleigh Faith An experiment or clinical trial that includes a comparison (control) group. [NCIT_14.05d] Research Activity Used for original studies with a control group, i.e. in which previously defined groups are compared with each other. Also used for studies with control material or control procedures. Retrospective studies may also be included. [Emtree_2014] controlled interrupted time series correlational design correlation design correlation designs correlation studies correlation study correlation trial correlation trials correlational designs correlational studies correlational study correlational trial correlational trials cross-over design D018592 Research Activity Studies comparing two or more treatments or interventions in which the subjects or patients, upon completion of the course of one treatment, are switched to another. In the case of two treatments, A and B, half the subjects are randomly allocated to receive these in the order A, B and half to receive them in the order B, A. A criticism of this design is that effects of the first treatment may carry over into the period when the second is given. [MeSH_2014] cross over study cross-over designs cross-over studies cross-over study cross-over study designs cross-over trial cross-over trials crossover design crossover designs crossover procedure crossover studies crossover study crossover study design crossover trial crossover trials procedure, crossover A type of clinical study in which each study subject receives the same series of treatments but in a random order that differs across arms of the study. Each subject serves as their own control in this type of study. [NCIT_14.05d] C82637 Tanja Bekhuis C0150097 Participants receive one of two or more alternative intervention(s) during the initial epoch of the study and receive other intervention(s) during the subsequent epoch(s) of the study. [NCIT_14.05d] [Contributing_Source_CDISC] A crossover design, sometimes called a counterbalanced design, is a type of experimental design in which every subject is exposed to every treatment in a balanced fashion. If there are just two treatments, at Time 1 half of the subjects receive Treatment A and the other half receive Treatment B. At Time 2 they ‘cross over,’ with the first half receiving Treatment B and the second half receiving Treatment A. Crossover designs are ‘Latin square’ designs in which each of k treatments is administered to each of k groups of subjects at k points in time (where k is equal to or greater than 2). They can also be used in assessing reliability when parallel forms are used. [Dictionary of nursing theory and research_2010] Crossover Cross-over cross-sectional study Ashleigh Faith D003430 Studies in which the presence or absence of disease or other health-related variables are determined in each member of the study population or in a representative sample at one particular time. [MeSH_2014] cross sectional design cross sectional designs cross sectional studies cross sectional study cross sectional trial cross sectional trials cross-sectional design cross-sectional designs cross-sectional research cross-sectional studies cross-sectional survey cross-sectional trial cross-sectional trials Epidemiologic methods [1975-1989] Longitudinal studies C0010362 Research Activity A study in which participants are examined at only a single time for characteristics of a disease. [NCIT_14.05d] C53310 cross sectional design database study data base design data base designs data base studies data base study data base trial data base trials database design database designs database studies database trial database trials descriptive study descriptive design descriptive designs descriptive research descriptive studies descriptive trial descriptive trials diagnostic study diagnostic design diagnostic designs diagnostic studies diagnostic trial diagnostic trials diagnostic test accuracy study diagnostic test accuracy studies dictionary dictionaries A reference book containing a list of words - usually in alphabetical order - giving information about form, pronunciation, etymology, grammar, and meaning. A foreign-language dictionary is an alphabetical list of words of one language with their meaning and equivalents in another language. [MeSH_2014] Intellectual Product C0012108 Ashleigh Faith D016437 C49461 Classification Manufactured Object Terminology directory directories published directories published directory Ashleigh Faith Manufactured Object Registries C0920318 C49057 A document that points out the location of people, places, or objects. [NCIT_14.05d] Intellectual Product Registers D016435 Registry Register Work consisting of an alphabetical or classified list of names, organizations, subjects, etc., giving usually titles, addresses, affiliations, and other professional data. [MeSH_2014] disease frequency survey disease frequency surveys surveys, disease frequency double blind clinical design double blind clinical designs double blind clinical studies double blind clinical study double blind clinical trial double blind clinical trials double-blind clinical design double-blind clinical designs double-blind clinical studies double-blind clinical study double-blind clinical trial double-blind clinical trials D004311 Ashleigh Faith Research Activity double blind comparison double-blind comparison D004311 Research Activity Ashleigh Faith double blind crossover design double blind crossover design double blind crossover designs double blind crossover studies double blind crossover study double blind crossover trial double blind crossover trials double-blind crossover design double-blind crossover designs double-blind crossover studies double-blind crossover study double-blind crossover trial double-blind crossover trials Research Activity D004311 Ashleigh Faith double blind design double blind designs double blind studies double blind study double blind test double blind tests double blind trial double blind trials double masked design double masked designs double masked studies double masked study double masked trial double masked trials double-blind design double-blind designs double-blind studies double-blind study double-blind test double-blind tests double-blind trial double-blind trials double-masked design double-masked designs double-masked studies double-masked study double-masked trial double-masked trials D004311 double-blind method Research Activity A method of studying a drug or procedure in which both the subjects and investigators are kept unaware of who is actually getting which specific treatment. [Double-blind method | MeSH_2014] Ashleigh Faith double blind method double blind randomized controlled trial double blinded randomised controlled design double blinded randomised controlled designs double blinded randomised controlled studies double blinded randomised controlled study double blinded randomised controlled trial double blinded randomised controlled trials double blinded randomized controlled design double blinded randomized controlled designs double blinded randomized controlled studies double blinded randomized controlled study double blinded randomized controlled trials double blinded rct double blinded rcts double-blinded randomised controlled design double-blinded randomised controlled designs double-blinded randomised controlled studies double-blinded randomised controlled study double-blinded randomised controlled trial double-blinded randomised controlled trials double-blinded randomized controlled design double-blinded randomized controlled designs double-blinded randomized controlled studies double-blinded randomized controlled study double-blinded randomized controlled trial double-blinded randomized controlled trials double-blinded rct double-blinded rcts Research design [1977-1989] D004311 double blinded randomized controlled trial Ashleigh Faith A method of studying a drug or procedure in which both the subjects and investigators are kept unaware of who is actually getting which specific treatment. [Double-blind method | MeSH_2014] Research Activity duplicate publication duplicate publications Work consisting of an article or book of identical or nearly identical material published simultaneously or successively to material previously published elsewhere, without acknowledgment of the prior publication. [MeSH_2014] Ashleigh Faith Intellectual Product D016438 ecological cross-sectional study ecological cross sectional design ecological cross sectional designs ecological cross sectional studies ecological cross sectional study ecological cross sectional trial ecological cross sectional trials ecological cross-sectional design ecological cross-sectional designs ecological cross-sectional studies ecological cross-sectional trial ecological cross-sectional trials ecological study ecological design C53307 a statistical study exploring hypotheses by comparing groups, rather than individuals, e.g., comparing rates of breast cancer and levels of fat intake by country. [Dorland's illustrated medical dictionary_2011] population-based study ecological designs ecologic studies ecologic study ecological studies C1709599 Tanja Bekhuis population based study editorial editorials D016421 Work consisting of a statement of the opinions, beliefs, and policy of the editor or publisher of a journal, usually on current matters of medical or scientific significance to the medical community or society at large. The editorials published by editors of journals representing the official organ of a society or organization are generally substantive. [MeSH_2014] Ashleigh Faith Intellectual Product epidemiological design Ashleigh Faith D016021 Research Activity Studies designed to examine associations, commonly, hypothesized causal relations. They are usually concerned with identifying or measuring the effects of risk factors or exposures. [MeSH_2014] epidemiologic design epidemiologic designs epidemiologic studies epidemiologic study epidemiologic trial epidemiologic trials epidemiological designs epidemiological studies epidemiological study epidemiological trial epidemiological trials studies, epidemiologic Epidemiological methods involve sophisticated statistics and higher mathematics. These methods allow epidemiologists to address issues like non-experimental studies of mechanistic questions in disease etiology, including studies of the impact of the social position of individuals in different social contexts.[Epidemiological method | NCIT_14.05d] Epidemiological Method Epidemiology, Method C16555 C0014503 Epidemiological Technique erratum Corrigenda Published Erratum erratum = Item reporting an error, correction or retraction of a previously published paper [Emtree Scope Note, April 14, 2015] D016425 errata Tanja Bekhuis Work consisting of an acknowledgment of an error, issued by a publisher, editor, or author. It customarily cites the source where the error occurred, giving complete bibliographic data for retrieval. In the case of books and monographs, author, title, imprint, paging, and other helpful references will be given; in the case of journal articles, the author, title, paging, and journal reference will be shown. An erratum notice is variously cited as Errata or Corrigenda. [MeSH_2015] April 14, 2015 evaluation Tanja Bekhuis evaluation studies evaluation study evaluation design evaluation designs D005069 Studies determining the effectiveness or value of processes, personnel, and equipment, or the material on conducting such studies. [Evaluation Studies as Topic | MeSH_2015] evaluations November 18, 2014 Research Activity evidence report evidence report evidence reports report of evidence evidence report evidence reports report of evidence ex post facto design ex post facto designs ex post facto studies ex post facto study ex post facto trial ex post facto trials experimental design experimental designs experimental studies experimental study experimental trial experimental trials Experimental Design C15320 Study Design Describes the role the study plays in determining the interventions a subject receives. [NCIT_14.05d] [Contributing_Source_CDISC] A plan detailing how a study will be performed in order to represent the phenomenon under examination, to answer the research questions that have been asked, and defining the methods of data analysis. Study design is driven by research hypothesis being posed, study subject/population/sample available, logistics/resources: technology, support, networking, collaborative support, etc. [Study design | NCIT_14.05d] Research Activity Experiment Design C0035171 face-to-face interview face-to-face interviews factorial design factorial designs factorial studies factorial study factorial trial factorial trials Factorial Two or more interventions, each alone and in combination, are evaluated in parallel against a control group. [NCIT_14.05d] [Contributing_Source_CDISC] C2826344 C82638 Research Activity A type of clinical study in which two or more treatments are given alone and in combination, such that all possible combinations are represented across the treatment arms, and are compared in parallel against the study control group. [NCIT_14.05d] Ashleigh Faith feasibility study feasibility trial feasibility studies feasibility designs feasibility design feasibility trials festschrift festschriften Work consisting of a collection of essays or other writings contributed by students, teachers, colleagues, and associates to honor a person or institution, usually on the occasion of an anniversary celebration or other event of importance. [MeSH_2014] Historical Biography (1966-1990) Current Biog-Obit (1966-1990) Festschriften D016221 Intellectual Product Ashleigh Faith field survey Research Activity Tanja Bekhuis A descriptive or analytic study of risk factors or disease determinants in populations. Most epidemiologic and some genetic studies fit within this category. [NCIT_14.08d] C39404 C1517184 field surveys file review review of files focus group A method of data collection and a qualitative research tool in which a small group of individuals are brought together and allowed to interact in a discussion of their opinions about topics, issues, or questions. [MeSH_2014] Ashleigh Faith D017144 Group focus groups follow-up study government publication government publications Government Document D022903 Ashleigh Faith Intellectual Product Works consisting of documents issued by local, regional, or national governments or by their agencies or subdivisions. [MeSH_2014] Government Documents Manufactured Object group randomized design group randomised design group randomised designs group randomised studies group randomised study group randomised trial group randomised trials group randomized designs group randomized studies group randomized study group randomized trial group randomized trials head to head design head to head designs head to head studies head to head study head to head trial head to head trials head-to-head design head-to-head designs head-to-head studies head-to-head study head-to-head trial head-to-head trials health care survey healthcare surveys health care surveys Research Activity Statistical measures of utilization and other aspects of the provision of health care services including hospitalization and ambulatory care. [Health care surveys | MeSH_2014] Tanja Bekhuis healthcare survey D019538 health survey A systematic collection of factual data pertaining to health and disease in a human population within a given geographic area. [Health surveys | MeSH_2014] health surveys Research Activity Tanja Bekhuis D006306 historical article historical articles D016456 historical survey Ashleigh Faith Intellectual Product An article or portion of an article giving an account of past events or circumstances significant in a field of study, a profession, a discovery, an invention, etc. The concept of history is very wide, ranging from the dawn of time to the present. This publication type is often checked in conjunction with BIOGRAPHY. [MeSH_2014] historically controlled design historically controlled designs historically controlled studies historically controlled study historically controlled trial historically controlled trials historical control trial historical control studies November 7, 2014 Quantitative Concept A study that compares a group of participants receiving an intervention with a similar group from the past who did not. [Historically Controlled Study | MeSH_2015] Research Activity historical control designs historical control study Tanja Bekhuis historical control design D065386 historical control trials hospital-based case control design hospital based case control design hospital based case control studies hospital based case control study hospital based case control trial hospital based case-control design hospital based case-control studies hospital based case-control study hospital based case-control trial hospital-based case control designs hospital-based case control studies hospital-based case control study hospital-based case control trials hospital-based case-control designs hospital-based case-control studies hospital-based case-control study hospital-based case-control trials human study human experiment human experiments human studies in vitro study in vitro studies in vitro designs in vitro design in vivo study in vivo studies in vivo design in vivo designs incidence study incidence studies index indices indexes interactive tutorial interactive media interactive tutorials D054710 Interactive Media Video recordings or other files in which the progress of the instruction or content is determined by user response. [MeSH_2014] Ashleigh Faith Intellectual Product interrupted time series design interrupted time series designs interrupted time series studies interrupted time series study interrupted time series trial interrupted time series trials interrupted time series analyses Quantitative Concept ITS study D065186 interrupted time series A study that uses observations at multiple time points before and after an intervention (the "interruption"), in an attempt to detect whether the intervention has had an effect significantly greater than any underlying trend over time. [Interrupted Time Series Analysis | MeSH_2015] Research Activity November 7, 2014 Tanja Bekhuis interrupted time series analysis ITS studies interrupted time series with comparison group interrupted time series with comparison groups interrupted time series without comparison group interrupted time series without comparison groups interview interviewing interviews Research Activity D017203 Intellectual Product Work consisting of a conversation with an individual regarding his or her background and other personal and professional details, opinions on specific subjects posed by the interviewer, etc. [MeSH_2014] C16751 oral history A conversation with an individual regarding his or her background and other personal and professional details, opinions on specific subjects posed by the interviewer, etc. [NCIT_14.05d] C0021822 Occupational Activity Ashleigh Faith interview interview study D017203 Research Activity interviews Work consisting of a conversation with an individual regarding his or her background and other personal and professional details, opinions on specific subjects posed by the interviewer, etc. [MeSH_2014] Intellectual Product oral history C16751 interviewing interview studies Ashleigh Faith Occupational Activity A conversation with an individual regarding his or her background and other personal and professional details, opinions on specific subjects posed by the interviewer, etc. [NCIT_14.05d] C0021822 introductory journal article introductory journal articles prefatory journal article prefatory journal articles Prefatory Journal Article Prefactory summary to a special issue or section of a journal devoted to a specific topic. This introductory text can be of varying length and substance. [MeSH_2014] D054711 Intellectual Product Ashleigh Faith journal article journal articles The predominant publication type for articles and other items indexed for NLM databases. [MeSH_2015] Intellectual Product November 13, 2014 D016428 Tanja Bekhuis lecture lectures D019531 Intellectual Product Ashleigh Faith Works consisting of speeches read or delivered before an audience or class, especially for instruction or to set forth some subject. They are differentiated from ADDRESSES [PUBLICATION TYPE] which are less didactic and more informational, entertaining, inspirational, or polemic. (From Random House Unabridged Dictionary, 2d ed) [MeSH_2014] legislation legislations Legal case D020485 Legal cases Works consisting of the text of proposed or enacted legislation that may be in the form of bills, laws, statutes, ordinances, or government regulations.CATALOG: use when 20% or more of the content consists of the text of laws, statutes, ordinances, or government regulations. Do not use for works that are merely discussion of law, etc. [MeSH_2014] Intellectual Product Ashleigh Faith letter Collected Correspondence A written message addressed to a person or organization. [NCIT_14.05d] [Contributing_Source_ FDA] Work consisting of written or printed communication between individuals or between persons and representatives of corporate bodies. The correspondence may be personal or professional. In medical and other scientific publications the letter is usually from one or more authors to the editor of the journal or book publishing the item being commented upon or discussed. LETTER is often accompanied by COMMENT. [MeSH_2014] Intellectual Product Manufactured Object C1096774 Ashleigh Faith D016422 C70805 letter to the editor letters to the editor literature review review, academic D016454 review literature reviews review of literature review review of reported cases literature reviews An article or book published after examination of published material on a subject. It may be comprehensive to various degrees and the time range of material scrutinized may be broad or narrow, but the reviews most often desired are reviews of the current literature. The textual material examined may be equally broad and can encompass, in medicine specifically, clinical material as well as experimental research or case reports. State-of-the-art reviews tend to address more current matters. [MeSH_2014] Significant review of original research. [Emtree_2014] Ashleigh Faith review, multicase Intellectual Product longitudinal design longitudinal designs longitudinal evaluation longitudinal studies longitudinal study longitudinal survey longitudinal trial longitudinal trials Studies in which variables relating to an individual or group of individuals are assessed over a period of time. [MeSH_2014] Research Activity D008137 Ashleigh Faith Quantitative Concept Epidemiologic Methods [1966-1974] a study in which participants, processes, or systems are studied over time, with data being collected at multiple intervals. The two main types are prospective s. and retrospective s. Cf. cross-sectional study [Emtree_2014] [Doralnd's Medaical Dictionary_2011] matched case control design matched case control matched case control designs matched case control studies matched case control study matched case control trial matched case control trials matched case-control design matched case-control designs matched case-control studies matched case-control study matched case-control trial matched case-control trials Ashleigh Faith D016022 Research Activity medical audit Audits, Medical Med Audit Health Care Activity Hospital Administration [1966-1967] Audit, Medical D008485 Ashleigh Faith A detailed review and evaluation of selected clinical records by qualified professional personnel for evaluating quality of medical care. [MeSH_2014] Medical Audits medical record review medical records review review of medical records meta-analysis meta analyses January 7, 2015 Tanja Bekhuis meta analysis metaanalyses meta-analyses Intellectual Product D017418 Works consisting of studies using a quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc. It is often an overview of clinical trials. It is usually called a meta-analysis by the author or sponsoring body and should be differentiated from reviews of literature. [MeSH_2015] metaanalysis meta-analysis Ashleigh Faith analysis, meta meta analysis metaanalysis meta-analyses C0920317 Research Activity metaanalyses A set of statistical procedures designed to accumulate experimental and correlational results across independent studies that address a related set of research questions. [NCIT_14.05d] Used for original reports evaluating medical interventions by the statistical analysis of a large collection of analysis results from individual studies, for the purpose of integrating the findings; not limited to clinical trials. [Emtree_2014] meta analyses The formal evaluation of the quantitative evidence from two or more trials bearing on the same question. NOTE: This most commonly involves the statistical combination of summary statistics from the various trials, but the term is sometimes also used to refer to the combination of the raw data. [from ICH E9 Glossary] [NCIT_14.05d] [Contributing_Source_CDISC] C17886 meta analysis of individual participant data individual patient data meta analysis individual patient data meta-analysis individual patient data metaanalysis individual patient data review ipd meta analysis ipd meta-analysis ipd metaanalysis ipd review meta analysis of individual patient data meta-analysis of individual participant data meta-analysis of individual patient data metaanalysis of individual participant data metaanalysis of individual patient data mipd review of individual patient data multiple case study multiple case report narrative review narrative reviews narrative review narrative reviews natural experiment natural experiments December 3, 2014 Tanja Bekhuis A naturally occurring situation that has many of the trappings of a formal laboratory experiment in that one can identify factors that function as independent variables although they are not controlled in the usual sense. For example, one could study the role of schooling in vocabulary development in children by comparing the number of new words learned during the summer with the number learned during the months just preceding and following. [Penguin Dictionary of Psychology_2009] nested case control design nested case control designs nested case control studies nested case control study nested case control trial nested case control trials nested case-control design nested case-control designs nested case-control studies nested case-control study nested case-control trial nested case-control trials Research Activity C0027775 C48202 Ashleigh Faith A study in which a group or cohort of individuals is followed for a certain length of time or until a specific outcome is reached. Studies of this type incorporate the strengths of both cohort and case-control studies but eliminates a portion of the methodologic challenges inherent in both types of studies. [NCIT_14.05d] non-comparative design non-comparative designs non-comparative studies non-comparative study non-comparative trial non-comparative trials noncomparative design noncomparative designs noncomparative studies noncomparative study noncomparative trial noncomparative trials nonconcurrent cohort study non-concurrent cohort design non-concurrent cohort designs non-concurrent cohort studies non-concurrent cohort study non-concurrent cohort trial non-concurrent cohort trials nonconcurrent cohort design nonconcurrent cohort designs nonconcurrent cohort studies nonconcurrent cohort trial nonconcurrent cohort trials non-controlled design non-controlled designs non-controlled studies non-controlled study non-controlled trial non-controlled trials noncontrolled design noncontrolled designs noncontrolled studies noncontrolled study noncontrolled trial noncontrolled trials uncontrolled design uncontrolled designs uncontrolled studies uncontrolled study uncontrolled trial uncontrolled trials non-equivalent control group design non-equivalent control group designs non-experimental design non-experimental designs non-experimental studies non-experimental study non-experimental trial non-experimental trials nonexperimental design nonexperimental designs nonexperimental studies nonexperimental study nonexperimental trial nonexperimental trials non-randomized clinical trial nonrandomised clinical trial clinical trials, non-randomized nonrandomised clinical trials clinical trial, non-randomised clinical trials, nonrandomized clinical trials, nonrandomised clinical trials, non-randomised non-randomised clinical trials nonrandomized clinical trial non-randomized clinical trials clinical trial, non-randomized clinical trial, nonrandomized non-randomised clinical trial nonrandomized clinical trials clinical trial, nonrandomised non-randomized comparative design non-randomised comparative design non-randomised comparative designs non-randomised comparative studies non-randomised comparative study non-randomised comparative trial non-randomised comparative trials non-randomized comparative designs non-randomized comparative studies non-randomized comparative study non-randomized comparative trial non-randomized comparative trials nonrandomised comparative design nonrandomised comparative designs nonrandomised comparative studies nonrandomised comparative study nonrandomised comparative trial nonrandomised comparative trials nonrandomized comparative design nonrandomized comparative designs nonrandomized comparative studies nonrandomized comparative study nonrandomized comparative trial nonrandomized comparative trials non-randomized controlled design non-randomised controlled design non-randomised controlled designs non-randomised controlled studies non-randomised controlled study non-randomised controlled trial non-randomised controlled trials non-randomized controlled designs non-randomized controlled studies non-randomized controlled study non-randomized controlled trial non-randomized controlled trials nonrandomised controlled design nonrandomised controlled designs nonrandomised controlled studies nonrandomised controlled study nonrandomised controlled trial nonrandomised controlled trials nonrandomized controlled design nonrandomized controlled designs nonrandomized controlled studies nonrandomized controlled study nonrandomized controlled trial nonrandomized controlled trials November 7, 2014 D065228 Tanja Bekhuis Research Activity Quantitative Concept A study where participants are assigned to a treatment, procedure, or intervention my methods that are not random. Non-randomized clinical trials are sometimes referred to as quasi-experimental clinical trials or non-equivalent control group designs. [Non-Randomized Controlled Trials as Topic | MeSH_2015] non-randomized cross-over design non-randomised cross-over design non-randomised cross-over designs non-randomised cross-over studies non-randomised cross-over study non-randomised cross-over trial non-randomised cross-over trials non-randomised crossover design non-randomised crossover designs non-randomised crossover studies non-randomised crossover study non-randomised crossover trial non-randomised crossover trials non-randomized cross-over designs non-randomized cross-over studies non-randomized cross-over study non-randomized cross-over trial non-randomized cross-over trials non-randomized crossover design non-randomized crossover designs non-randomized crossover studies non-randomized crossover study non-randomized crossover trial non-randomized crossover trials nonrandomised cross-over design nonrandomised cross-over designs nonrandomised cross-over studies nonrandomised cross-over study nonrandomised cross-over trial nonrandomised cross-over trials nonrandomised crossover design nonrandomised crossover designs nonrandomised crossover studies nonrandomised crossover study nonrandomised crossover trial nonrandomised crossover trials nonrandomized cross-over design nonrandomized cross-over designs nonrandomized cross-over studies nonrandomized cross-over study nonrandomized cross-over trial nonrandomized cross-over trials nonrandomized crossover design nonrandomized crossover designs nonrandomized crossover studies nonrandomized crossover study nonrandomized crossover trial nonrandomized crossover trials non-randomized design non-randomised design non-randomised designs non-randomised studies non-randomised study non-randomised trial non-randomised trials non-randomized designs non-randomized studies non-randomized study non-randomized trial non-randomized trials nonrandomised design nonrandomised designs nonrandomised studies nonrandomised study nonrandomised trial nonrandomised trials nonrandomized design nonrandomized designs nonrandomized studies nonrandomized study nonrandomized trial nonrandomized trials nonconsecutive case series C2985409 Research Activity A clinical study that includes some, but not all, of the eligible patients identified by the researchers during the study registration period. This type of study does not usually have a control group. [NCIT_14.08d] C93042 observational study observation design observation designs observation studies observation study observation trial observation trials observational design observational designs observational studies observational trial observational trials Studies in which biomedical and/or health outcomes are assessed in pre-defined groups of individuals. Subjects in the study may receive diagnostic, therapeutic, or other interventions, but the investigator does not assign specific interventions to the subjects of the study. [NCIT_14.05d] [Contributing_Source_CDISC] A type of study in which individuals are observed or certain outcomes are measured. No attempt is made to affect the outcome (for example, no treatment is given). [NCIT_14.05d] C1518527 Studies among cancer patients and healthy populations that involve no intervention or alteration in the status of the participants. [NCIT_14.05d] C16084 Research Activity open clinical design open clinical designs open clinical studies open clinical study open clinical trial open clinical trials open design open designs open studies open study open trial open trials open label clinical design open label clinical designs open label clinical studies open label clinical study open label clinical trial open label clinical trials open-label clinical design open-label clinical designs open-label clinical studies open-label clinical study open-label clinical trial open-label clinical trials open label design open label designs open label studies open label study open label trial open label trials open-label design open-label designs open-label studies open-label study open-label trial open-label trials open label randomized controlled trial open label randomised controlled design open label randomised controlled designs open label randomised controlled studies open label randomised controlled study open label randomised controlled trial open label randomised controlled trials open label randomized controlled design open label randomized controlled designs open label randomized controlled studies open label randomized controlled study open label randomized controlled trials open label rct open label rcts open-label randomised controlled design open-label randomised controlled designs open-label randomised controlled studies open-label randomised controlled study open-label randomised controlled trial open-label randomised controlled trials open-label randomized controlled design open-label randomized controlled designs open-label randomized controlled studies open-label randomized controlled study open-label randomized controlled trial open-label randomized controlled trials open-label rct open-label rcts open label randomized controlled trial opinion paper opinion papers discussion papers opinion piece opinion pieces discussion pieces discussion piece discussion paper overview of reviews overview reviews overview review overview of reviews overview reviews overview review parallel design parallel designs parallel studies parallel study parallel trial parallel trials C2826345 Participants are assigned to one of two or more arms in parallel for the duration of the study. [NCIT_14.05d] [Contributing_Source_CDISC] C82639 A type of clinical study in which subjects are assigned to one of two treatment arms at the beginning of the trial and continue in that arm throughout the length of the trial. Study subjects are only exposed to the treatment that is assigned to the particular study arm they are enrolled in. [NCIT_14.05d] Research Activity patient education handout patient education handouts D029282 Intellectual Product Consumer Handout Ashleigh Faith Consumer Information Handout Works consisting of a handout or self-contained informative material used to explain a procedure or a condition or the contents of a specific article in a biomedical journal and written in non-technical language for the patient or consumer. [MeSH_2014] Manufactured Object periodical index Work consisting of a subject approach to the contents of a periodical issuing an annual, biennial, quinquennial, decennial, etc., index. The heading is used for the overall body of articles published by a periodical in the same sense that BIBLIOGRAPHY is useful when published as a single article. [MeSH_2014] periodical indexes D016453 periodical indices Intellectual Product Ashleigh Faith Bibliography (1968-1989) phase III trial phase IIIa trial phase IIIb trial phase II trial phase IIa trial trial phase IIa trial phase 2a phase IIb trial phase IV trial A randomized, controlled trial that is designed to evaluate the long-term safety and efficacy of a drug for a given indication. Often they are designed to study side effects that may have become apparent after the phase III study was completed. [NCIT_14.08d] Phase IV Clinical Trials C0282462 Tanja Bekhuis Clinical Trials, Phase IV Phase 4. Postmarketing (Phase 4) studies to delineate additional information about the drug's risks, benefits, and optimal use that may be requested by regulatory authorities in conjunction with marketing approval. NOTE: These studies could include, but would not be limited to, studying different doses or schedules of administration than were used in Phase 2 studies, use of the drug in other patient populations or other stages of the disease, or use of the drug over a longer period of time. [After FDA CDER Handbook, ICH E8] [Contributing Source_CDISC] [NCIT_14.08d] Phase 4 Study Research Activity After a treatment has been approved and is being marketed, it is studied in a phase IV trial to evaluate side effects that were not apparent in the phase III trial. Thousands of people are involved in a phase IV trial. [NCIT_14.08d] phase IV clinical trial Phase 4 Studies C15603 Trial Phase 4 Clinical Trial, Phase IV phase I trial Clinical Trials, Phase I Phase I Study Early-Stage Clinical Trials Phase 1 Study C0920321 Trial Phase 1 C15600 Research Activity Phase I Protocol Phase I Clinical Trials pilot study Research Activity pilot projects Tanja Bekhuis November 7, 2014 Small-scale tests of methods and procedures to be used on a larger scale if the pilot study demonstrates that these methods and procedures can work. [Pilot Projects | MeSH_2015] pilot project D010865 pilot studies population surveillance Health Care Activity D011159 Research Activity Tanja Bekhuis Ongoing scrutiny of a population (general population, study population, target population, etc.), generally using methods distinguished by their practicability, uniformity, and frequently their rapidity, rather than by complete accuracy. [MeSH_2014] pragmatic clinical trial Research Activity pragmatic clinical designs Tanja Bekhuis pragmatic clinical studies pragmatic clinical study November 7, 2014 Intellectual Product D065007 pragmatic clinical trials pragmatic clinical design Randomized clinical trials that compare interventions in clinical settings and which look at a range of effectiveness outcomes and impacts. [MeSH_2015] pragmatic design pragmatic designs pragmatic studies pragmatic study pragmatic trial pragmatic trials pre-and-post design pre-and-post designs pre-and-post studies pre-and-post study pre-and-post trial pre-and-post trials pre-post design pre-post designs pre-post studies pre-post study pre-post tests pre-post trial pre-post trials pre-test post-test design pre-test post-test designs pre-test post-test studies pre-test post-test study pre-test post-test trial pre-test post-test trials pretest posttest design pretest posttest designs pretest posttest studies pretest posttest study pretest posttest trial pretest posttest trials pre-test post-test control group design pre-test post-test control group designs pre-test post-test control group studies pre-test post-test control group study pre-test post-test control group trial pre-test post-test control group trials pretest posttest control group design pretest posttest control group designs pretest posttest control group studies pretest posttest control group study pretest posttest control group trial pretest posttest control group trials prevalence study prevalence studies D003430 Research Activity Epidemiologic methods [1975-89] Ashleigh Faith Quantitative Concept prospective case series prospective cohort study prospective cohort design prospective cohort designs prospective cohort studies prospective cohort trial prospective cohort trials C0033522 A research study that follows over time groups of individuals who are alike in many ways but differ by a certain characteristic (for example, female nurses who smoke and those who do not smoke) and compares them for a particular outcome (such as lung cancer). [NCIT_14.05d] Ashleigh Faith Research Activity C53308 prospective study prospective studies Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group. [MeSH_2014] Ashleigh Faith study, prospective a longitudinal epidemiologic study in which the groups of individuals (cohorts) are selected on the basis of factors that are to be examined for their effects on outcomes, e.g., the effect of exposure to a specific risk factor on the eventual development of a particular disease, and are then followed over a period of time to determine the incidence rates of the outcomes in question in relation to the original factors. Called also cohort s.“Prospective” usually implies a cohort selected in the present and followed into the future, but the cohort method can also be applied to existing longitudinal historical data, such as insurance or medical records: a cohort is identified and classified as to exposure to some factor at some date in the past and followed up to the present to determine incidence rates of the outcome. This is called a historical prospective study, prospective study of past data, or retrospective cohort study. [Emtree_2014] [ Dorland's Medical Dictionary_2011] Research Activity D011446 prospective method psychometric study psychometric design psychometric designs psychometric studies psychometric trial psychometric trials Tanja Bekhuis [A study based on ... ] The science of measuring "psychological" aspects of a person such as knowledge, skills, abilities, or personality. Measurement of these unobservable phenomena is difficult and much of the research and accumulated art of this discipline is designed to reliably define and then quantify. [psychometrics | NCIT_14.10d] C17034 November 18, 2014 public health surveillance Research Activity Tanja Bekhuis The ongoing, systematic collection, analysis, and interpretation of health-related data with the purpose of preventing or controlling disease or injury, or of identifying unusual events of public health importance, followed by the dissemination and use of information for public health action. [From Am J Prev Med 2011;41(6):636] [MeSH_2014] population surveillance Health Care Activity D062486 published erratum corrigenda errata Work consisting of an acknowledgment of an error, issued by a publisher, editor, or author. It customarily cites the source where the error occurred, giving complete bibliographic data for retrieval. In the case of books and monographs, author, title, imprint, paging, and other helpful references will be given; in the case of journal articles, the author, title, paging, and journal reference will be shown. An erratum notice is variously cited as Errata or Corrigenda. [MeSH_2014] D016425 Ashleigh Faith Intellectual Product qualitative evaluation qualitative evaluations qualitative study qualitative design Ashleigh Faith qualitative designs qualitative studies D036301 Research that derives data from observation, interviews, or verbal interactions and focuses on the meanings and interpretations of the participants (From Holloway and Wheeler, "Ethical issues in qualitative nursing research," Nursing Ethics, 1995 Sep; 2(3): 223-232). [MeSH_2014] Research Activity quantitative evaluation quantitative evaluations quantitative study numerical studies quantitative studies quantitative design numerical study quantitative designs quasi-experimental clinical trial quasi-experimental clinical trial quasi-experimental design quasi experimental design quasi experimental designs quasi experimental studies quasi experimental study quasi experimental trial quasi experimental trials quasi-experimental designs quasi-experimental studies quasi-experimental study quasi-experimental trial quasi-experimental trials quasiexperimental design quasiexperimental designs quasiexperimental studies quasiexperimental study quasiexperimental trial quasiexperimental trials quasi randomized controlled design quasi randomised controlled design quasi randomised controlled designs quasi randomised controlled studies quasi randomised controlled study quasi randomised controlled trial quasi randomised controlled trials quasi randomized controlled designs quasi randomized controlled studies quasi randomized controlled study quasi randomized controlled trial quasi randomized controlled trials quasi rct quasi rcts quasi-randomised controlled design quasi-randomised controlled designs quasi-randomised controlled studies quasi-randomised controlled study quasi-randomised controlled trial quasi-randomised controlled trials quasi-randomized controlled design quasi-randomized controlled designs quasi-randomized controlled studies quasi-randomized controlled study quasi-randomized controlled trial quasi-randomized controlled trials quasi randomized design quasi randomised design quasi randomised designs quasi randomised studies quasi randomised study quasi randomised trial quasi randomised trials quasi randomized designs quasi randomized studies quasi randomized study quasi randomized trial quasi randomized trials quasi-randomised design quasi-randomised designs quasi-randomised studies quasi-randomised study quasi-randomised trial quasi-randomised trials quasi-randomized design quasi-randomized designs quasi-randomized studies quasi-randomized study quasi-randomized trial quasi-randomized trials randomized clinical trial randomised clinical design randomised clinical designs randomised clinical studies randomised clinical study randomised clinical trial randomised clinical trials randomized clinical design randomized clinical designs randomized clinical studies randomized clinical study randomized clinical trials C0206034 A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial. [NCIT_14.05d] Ashleigh Faith C15417 Used for original reports of prospective clinical studies in which the (comparative) efficacy of one or more medical interventions in humans is evaluated; also used for prospective clinical veterinary trials in which the (comparative) efficacy of one or more medical interventions in animals is evaluated. [Clinical trial | Embase_2014] Used as a drug subheading when the clinical trial of a drug is reported. [Clinical trial | Embase_2014] Research Activity randomized controlled clinical trial A study in which the participants are assigned by chance to separate groups to evaluate treatments. The study also includes a control group, which is undergoing the same rigors of the study with placebo treatment or standard treatment. The trial can also be controlled by the addition of a test group to ensure there are no factors present to skew the results and by the inclusion of peer-review analysis by appropriate government officials. [NCIT_14.08d] Tanja Bekhuis C0206035 Research Activity C46079 randomized controlled trial controlled trial, randomized randomised controlled trial randomised controlled design randomised controlled designs randomised controlled studies randomised controlled study randomised controlled trials randomized controlled designs randomized controlled studies randomized controlled study randomized controlled trial randomized controlled trials rct rcts trial, randomized controlled Ashleigh Faith randomized control trial Research Activity Work consisting of a clinical trial that involves at least one test treatment and one control treatment, concurrent enrollment and follow-up of the test- and control-treated groups, and in which the treatments to be administered are selected by a random process, such as the use of a random-numbers table. [MeSH_2014] randomized controlled design randomised control trial D016449 Intellectual Product randomized cross-over design randomized cross-over design randomised cross-over design randomised cross-over designs randomised cross-over studies randomised cross-over study randomised cross-over trial randomised cross-over trials randomised crossover design randomised crossover designs randomised crossover studies randomised crossover study randomised crossover trial randomised crossover trials randomized cross-over designs randomized cross-over studies randomized cross-over study randomized cross-over trial randomized cross-over trials randomized crossover design randomized crossover designs randomized crossover studies randomized crossover study randomized crossover trial randomized crossover trials randomized design randomised design randomised designs randomised studies randomised study randomised trial randomised trials randomized designs randomized studies randomized study randomized trial randomized trials rapid review rapid reviews rapid review rapid reviews registry study register study register studies registry studies reliability design reliability designs reliability studies reliability study reliability trial reliability trials research report research reports Intellectual Product Tanja Bekhuis Detailed account or statement or formal record of data resulting from empirical inquiry. [MeSH_2015] November 13, 2014 D058028 retracted publication retracted publications Ashleigh Faith Intellectual Product D016441 Work consisting of the designation of an article or book as retracted in whole or in part by an author or authors or an authorized representative. It identifies a citation previously published and now retracted through a formal issuance from the author, publisher, or other authorized agent, and is distinguished from RETRACTION OF PUBLICATION, which identifies the citation retracting the original published item. [MeSH_2014] retrospective case control design retrospective case control designs retrospective case control studies retrospective case control study retrospective case control trial retrospective case control trials retrospective case-control design retrospective case-control designs retrospective case-control studies retrospective case-control study retrospective case-control trial retrospective case-control trials retrospective case series retrospective cohort study historical cohort studies cohort study, historical retrospective cohort studies historic cohort study retrospective cohort trial Tanja Bekhuis historic cohort studies Research Activity study, historical cohort retrospective cohort trials historical cohort trials A research study in which the medical records of groups of individuals who are alike in many ways but differ by a certain characteristic (for example, female nurses who smoke and those who do not smoke) are compared for a particular outcome (such as lung cancer). [NCIT_14.08d] C2985505 historical cohort designs retrospective cohort designs studies, historical cohort cohort studies, historical retrospective cohort design historical cohort design C93228 historical cohort trial historical cohort study retrospective study Ashleigh Faith D012189 Quantitative Concept Studies used to test etiologic hypotheses in which inferences about an exposure to putative causal factors are derived from data relating to characteristics of persons under study or to events or experiences in their past. The essential feature is that some of the persons under study have the disease or outcome of interest and their characteristics are compared with those of unaffected persons. [MeSH_2014] retrospective design retrospective designs retrospective studies retrospective trial retrospective trials study, retrospective C53312 a longitudinal epidemiologic study in which participating individuals are classified as either having (cases) or lacking (controls) some outcome and their histories are examined for the presence of specific factors possibly associated with that outcome. Cases and controls are often matched with respect to certain demographic or other variables but need not be. As compared with prospective studies, retrospective studies suffer from drawbacks: although they can measure the odds ratio, which often approximates relative risk, they cannot reveal true incidence rates or attributable risk. Also, large biases can be introduced both in the selection of controls and in the recall of past exposure to risk factors. The advantage of the retrospective study is its small scale, usually short time for completion, and its applicability to rare diseases, which would require study of very large cohorts in prospective studies. [Emtree_2014] [ Dorland's Medical Dictionary_2011] retrospective design retrospective studies A study in which known outcomes are examined in hindsight using existing records. [NCIT_14.05d] C0035363 Research Activity A study that compares two groups of people: those with the disease or condition under study (cases) and a very similar group of people who do not have the disease or condition (controls). Researchers study the medical and lifestyle histories of the people in each group to learn what factors may be associated with the disease or condition. For example, one group may have been exposed to a particular substance that the other was not. [NCIT_14.05d] [Embase_2014] retrospective panel study retrospective panel studies literature review review review of reported cases review, multicase reviews D016454 review literature literature reviews review, academic review of literature Ashleigh Faith Intellectual Product Significant review of original research. [Emtree_2014] An article or book published after examination of published material on a subject. It may be comprehensive to various degrees and the time range of material scrutinized may be broad or narrow, but the reviews most often desired are reviews of the current literature. The textual material examined may be equally broad and can encompass, in medicine specifically, clinical material as well as experimental research or case reports. State-of-the-art reviews tend to address more current matters. [MeSH_2014] records review review of records record review scientific publication C19026 November 13, 2014 A class of publication in which original scientific work is described. The format usually includes an introduction in which relevant concepts are identified and the experimental system under study is presented, a section describing the experiments that were performed to test a specific hypothesis and the results and observations that were obtained, a section in which the results are discussed relative to findings by other investigators and the current state of knowledge in the field, and a section describing the experimental methods and procedures in sufficient detail to enable the reproduction of the work by independent investigators. [NCIT_14.10d] scientific publications Intellectual Product Tanja Bekhuis C1704324 scoping review scoping reviews scoping review scoping reviews semi-structured interview semistructured interview semistructured interviews semi-structured interviews sentinel surveillance Occupational Activity population surveillance Monitoring of rate of occurrence of specific conditions to assess the stability or change in health levels of a population. It is also the study of disease rates in a specific cohort such as in a geographic area or population subgroup to estimate trends in larger population. [From Last, Dictionary of Epidemiology, 2d ed] [MeSH_2014] D018571 Tanja Bekhuis single blind randomized controlled trial single blinded randomised controlled design single blinded randomised controlled designs single blinded randomised controlled studies single blinded randomised controlled study single blinded randomised controlled trial single blinded randomised controlled trials single blinded randomized controlled design single blinded randomized controlled designs single blinded randomized controlled studies single blinded randomized controlled study single blinded randomized controlled trial single blinded randomized controlled trials single blinded rct single blinded rcts single-blinded randomised controlled design single-blinded randomised controlled designs single-blinded randomised controlled studies single-blinded randomised controlled study single-blinded randomised controlled trial single-blinded randomised controlled trials single-blinded randomized controlled design single-blinded randomized controlled designs single-blinded randomized controlled studies single-blinded randomized controlled study single-blinded randomized controlled trial single-blinded randomized controlled trials single-blinded rct single-blinded rcts single case study n-of-1 design n-of-1 designs n-of-1 studies n-of-1 study n-of-1 trial n-of-1 trials n-of-one design n-of-one designs n-of-one studies n-of-one study n-of-one trial n-of-one trials single subject studies single-case designs single-case design single-subject trial single-case study single subject trials single-subject studies single-subject trials single case trials single-case trial single case trial single case designs single-case trials single case studies single-subject study single-subject designs single subject design single-case studies single-subject design single case design single case reports single subject study single case report single subject designs single subject trial solomon four group design solomon four group designs solomon four group studies solomon four group study solomon four group trial solomon four group trials solomon four-group design solomon four-group designs solomon four-group studies solomon four-group study solomon four-group trial solomon four-group trials stepped wedge design stepped wedge designs stepped wedge studies stepped wedge study stepped wedge trial stepped wedge trials structured interview structured interviews surveillance Tanja Bekhuis In medicine, the ongoing collection of information about a disease, such as cancer, in a certain group of people. The information collected may include where the disease occurs in a population and whether it affects people of a certain gender, age, or ethnic group. [NCIT_14.08d] Health Care Activity C15719 The systematic collection, analysis, and interpretation of health data on an ongoing basis. [NCIT_14.08d] survey surveys An examination or inspection carried out with specific aims in mind, a search for particular kinds of information. This sense is carried in a number of specific kinds of research designs in which questionnaires, inventories or interviews may be employed to gather information about attitudes, opinions or preferences in a society or some segment of it. [The Penguin Dictionary of Psychology, 2009] Tanja Bekhuis systematic review systematic review review, systematic systematic reviews Ashleigh Faith Used for studies that systematically summarize all relevant evidence pertaining to a defined health question, and including items identified as such by the author. [Emtree_2014] systematic review review, systematic systematic reviews Ashleigh Faith Used for studies that systematically summarize all relevant evidence pertaining to a defined health question, and including items identified as such by the author. [Emtree_2014] technical report Tanja Bekhuis Work consisting of a formal report giving details of the investigation and results of a medical or other scientific problem. When issued by a government agency or comparable official body, its contents may be classified, unclassified, or declassified with regard to security clearance. This publication type may also cover a scientific paper or article that records the current state or current position of scientific research and development. If so labeled by the editor or publisher, this publication type may be properly used for journal articles. [MeSH_2015] technical reports November 13, 2014 D016427 Intellectual Product theoretical design theoretical designs theoretical studies theoretical study time and motion study time and motion studies work sampling Ashleigh Faith D013996 work simplification performance, task task performance Task performance and analysis [1973-74] Intellectual Product task performance and analysis The observation and analysis of movements in a task with an emphasis on the amount of time required to perform the task. [MeSH_2014] time series design multiple time series time design time designs time series time series analysis time studies time study time trial time trials time series designs time series studies time series study [Embase_2014] [Dorland's Medical Dictionary_2011] trend design trend designs trend studies trend study trend trial trend trials umbrella review umbrella reviews umbrella review umbrella reviews uncontrolled longitudinal design uncontrolled longitudinal designs uncontrolled longitudinal studies uncontrolled longitudinal study uncontrolled longitudinal trial uncontrolled longitudinal trials validity design validation studies validation study validity designs validity studies validity study validity trial validity trials Ashleigh Faith D023361 Intellectual Product white paper white papers phase I/II trial Tanja Bekhuis trial phase1/2 C1519043 A clinical research protocol designed to study the safety, dosage levels and response to new treatment. Phase I/II trials combine a Phase I and a Phase II trial of the same treatment into a single protocol. [NCIT_14.08d] Research Activity C15693 trial phase 1-2 A class of clinical study that combines elements characteristic of traditional Phase I and Phase II trials. See also Phase I, Phase II. [NCIT_14.08d] [Contributing_Source_CDISC] A trial to study the safety, dosage levels, and response to a new treatment. [NCIT_14.08d] phase II/III trial trial phase 2/3 A class of clinical study that combines elements characteristic of traditional Phase II and Phase III trials. [NCIT_14.08d] [Contributing_Source_CDISC] Research Activity A type of clinical study that combines elements characteristic of traditional Phase II and Phase III trials. [NCIT_14.08d] C15694 Tanja Bekhuis trial phase 2-3 A trial to study response to a new treatment and the effectiveness of the treatment compared with the standard treatment regimen. [NCIT_14.08d] C1519042 "An antibody is a type of protein made by B lymphocytes in response to a foreign substance (antigen). Each antibody only binds to a specific antigen, helping to destroy the antigen directly or by assisting white blood cells to destroy the antigen." NCI C16295 'Antibody' An agency or organized group of individual that whose opinions influence policy decisions cytochrome P450, family 1, subfamily A, polypeptide 2. A heme-thiolate monooxygenase. UniProtKB/Swiss-Prot entry P05177 summarizes the properties of this enzyme in humans. The HUGO Gene Nomenclature Committee (HGNC) database uses 'CYP1A2' as the symbol for the gene that codes this protein. cytochrome P450, family 2, subfamily C, polypeptide 19. A heme-thiolate monooxygenase. UniProtKB/Swiss-Prot entry P33261 summarizes the properties of this enzyme in humans. The HUGO Gene Nomenclature Committee (HGNC) database uses 'CYP2C19' as the symbol for the gene that codes this protein. cytochrome P450, family 2, subfamily C, polypeptide 9. cytochrome P450, family 2, subfamily C, polypeptide 9. A heme-thiolate monooxygenase. UniProtKB/Swiss-Prot entry P11712 summarizes the properties of this enzyme in humans. The HUGO Gene Nomenclature Committee (HGNC) database uses 'CYP2C9' as the symbol for the gene that codes this protein. cytochrome P450, family 2, subfamily D, polypeptide 6. A heme-thiolate monooxygenase. UniProtKB/Swiss-Prot entry P10635 summarizes the properties of this enzyme in humans. The HUGO Gene Nomenclature Committee (HGNC) database uses 'CYP2D6' as the symbol for the gene that codes this protein. cytochrome P450, family 2, subfamily E, polypeptide 1. A heme-thiolate monooxygenase. UniProtKB/Swiss-Prot entry P05181 summarizes the properties of this enzyme in humans. The HUGO Gene Nomenclature Committee (HGNC) database uses 'CYP2E1' as the symbol for the gene that codes this protein. cytochrome P450, family 3, subfamily A; polypeptide 4. A heme-thiolate monooxygenase. UniProtKB/Swiss-Prot entry P08684 summarizes the properties of this enzyme in humans. The HUGO Gene Nomenclature Committee (HGNC) database uses 'CYP3A4' as the symbol for the gene that codes this protein. cytochrome P450, family 3, subfamily A; polypeptide 5. A heme-thiolate monooxygenase. UniProtKB/Swiss-Prot entry P20815 summarizes the properties of this enzyme in humans. The HUGO Gene Nomenclature Committee (HGNC) database uses 'CYP3A5' as the symbol for the gene that codes this protein. "The chemical reactions and pathways by which individual cells transform chemical substances." GO:0044237 Persons who have or are participating in a clinical trial "Cytochrome P450 isozymes, hemoprotein components of the mixed-function oxidase system involving electron and/or hydrogen transport through reversible valency change of the heme iron and metabolic biotransformation of substances, including foreign compounds to mutagens and carcinogens." Definition quote taken from NCI C26511 'Cytochrome_P450_Family_Gene', these are not synonomous types. Decreased area under the plot of plasma concentration of a drug against time after drug administration NCI C54609 (2006) NCI C54356 (2006) "A category of organic or inorganic substances, elements, and isotopes used in research or for the prevention, diagnosis, and /or treatment of disease states. Includes biologically active substances that are either synthetically manufactured or endogenous substances extracted and processed to be reintroduced into an organism. Chemicals and drugs also include hazardous substances, and naturally occurring or synthetically produced substances required to maintain life. (NCI04)" Maps to: NCI code: C1908, Instances of this class are also sub-types of NDF-RT "active ingredients" code: C178 The directed movement of a drug, a substance used in the diagnosis, treatment or prevention of a disease, into, out of, within or between cells. GO:0015893 (GO 2006) "Alteration of the disposition and/or effect of a drug, owing to the presence of another drug" NCI 2007 ID:C54708 "Alteration of the disposition and/or effect of a drug, owing to the presence of another factor such as a second drug, or food." NCI 2007 ID:C54708 a document produced by a drug 's manufacturer to accompany a drug's container or wrapper whose statements might include the drug's indications, effects, dosages, routes, methods, frequency and duration of administration, warnings, hazards, contraindications, side effects, precautions, and other relevant information. Adapted from MeSH 2007 "Drug Labeling" ID: D004348 A drug-label statement A firm that legally manufactures drug products for sale on the wholesale or retail market The chemical reactions and pathways involving a drug, a substance used in the diagnosis, treatment or prevention of a disease; as used here antibiotic substances (see antibiotic metabolism) are considered to be drugs, even if not used in medical or veterinary practice. GO:0017144 (2006) A study designed to quantify the pharmacokinetic and/or pharmacodynamic effects within study participants of a single drug (the object drug) in the presence of a purported precipitant. A DDI clinical trial Data from a study designed to quantify the pharmacokinetic and/or pharmacodynamic effects within study participants of a single drug (the object drug) in the presence of a purported precipitant. Material from a study designed to quantify the pharmacokinetic and/or pharmacodynamic effects within study participants of a single drug (the object drug) in the presence of a purported precipitant. A study designed to quantify the pharmacokinetic effects within study participants of a single drug in the presence of a purported precipitant. A study designed to quantify the pharmacokinetic effects within study participants of a single drug in the presence of a purported precipitant. Data from a study designed to quantify the pharmacokinetic effects within study participants of a single drug in the presence of a purported precipitant. Material from a study designed to quantify the pharmacokinetic effects within study participants of a single drug in the presence of a purported precipitant. A genotyped pharmacokinetic clinical trial A drug pharmacokinetics study whose population consists of at least two groups known to posses distinct forms of some drug-metabolizing enzyme Data from a drug pharmacokinetics study whose population consists of at least two groups known to posses distinct forms of some drug-metabolizing enzyme Material from a drug pharmacokinetics study whose population consists of at least two groups known to posses distinct forms of some drug-metabolizing enzyme A phenotyped pharmacokinetic clinical trial A drug pharmacokinetics study whose population consists of at least two groups known to posses distinct drug metabolizing phenotypes Data from a drug pharmacokinetics study whose population consists of at least two groups known to posses distinct drug metabolizing phenotypes Material from a drug pharmacokinetics study whose population consists of at least two groups known to posses distinct drug metabolizing phenotypes "A study of the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body." NCI code C49663 A pharmacokinetic clinical trial Data from a pharmacokinetic study, which is defined as: "A study of the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body." NCI code C49663 Material from a pharmacokinetic study, which is defined as: "A study of the process by which a drug is absorbed, distributed, metabolized, and eliminated by the body." NCI code C49663 An observation-based report of some occurrence An observation-based report An observation-based report of an adverse drug event An observation-based ADE report The data from an observation-based adverse drug event (ADE) report The material from an observation-based adverse drug event (ADE) report An adverse drug event report on file in a public adverse event reporting database such as the FDA's Adverse Event Reporting System An observation-based ADE report in a public reporting database The data from an observation-based adverse drug event (ADE) report on file in a public ADE reporting database such as the FDA's Adverse Event Reporting System The material from an observation-based adverse drug event (ADE) report on file in a public ADE reporting database such as the FDA's Adverse Event Reporting System An published observation-based case-report of a drug interaction A published observation-based ADE report The data from a published observation-based case-report of a drug interaction An observation-based report of a drug interaction that has been evaluated by some assesssment tool A published and evaluated observation-based ADE report The data from a published observation-based case-report of a drug interaction that has been evaluated by some assessment tool The material from a published observation-based case-report of a drug interaction that has been evaluated by some assessment tool The material from a published observation-based case-report of a drug interaction The data from an observation-based report of some occurrence The material from an observation-based report of some occurrence "a pre-planned clinical study of the safety, efficacy, or optimum dosage schedule of one or more diagnostic, therapeutic, or prophylactic drugs, devices, or techniques in humans selected according to predetermined criteria of eligibility and observed for predefined evidence of favorable and unfavorable effects." - Clinical Trial MeSH 2007 A clinical trial Data from a clinical trial, where a clinical trial is a: "a pre-planned clinical study of the safety, efficacy, or optimum dosage schedule of one or more diagnostic, therapeutic, or prophylactic drugs, devices, or techniques in humans selected according to predetermined criteria of eligibility and observed for predefined evidence of favorable and unfavorable effects." - Clinical Trial MeSH 2007 Material from a clinical trial, where a clinical trial is a: "a pre-planned clinical study of the safety, efficacy, or optimum dosage schedule of one or more diagnostic, therapeutic, or prophylactic drugs, devices, or techniques in humans selected according to predetermined criteria of eligibility and observed for predefined evidence of favorable and unfavorable effects." - Clinical Trial MeSH 2007 An FDA-sponsered review of a drug's pre-market studies and adverse event reports. An FDA clinical review A published analysis of research on the efficacy or safety of a drug, family of drugs, or drug therapy A drug review article A drug metabolism identification experiment -- an experiment conducted with biological tissues and/or chemical compounds in a laboratory designed to ``...identify the specific enzymes responsible for the metabolism of a drug'' (\cite{fda2006a}, p. 25) A drug metabolism identification experiment A metabolic enzyme identification experiment specifically designed to identify the Cytochrome P-450 enzymes involved in the metabolism of a drug A CYP450 drug metabolism identification experiment Data from a metabolic enzyme identification experiment specifically designed to identify the Cytochrome P-450 enzymes involved in the metabolism of a drug A Cytochrome P-450 metabolic enzyme identification experiment using human liver microsomes that have been characterized for Cytochrome P-450 activity A CYP450, human microsome, drug metabolism identification experiment A Cytochrome P-450 metabolic enzyme identification experiment using human liver microsomes that have been characterized for Cytochrome P-450 activity and antibodies as specific inhibitors A CYP450, human microsome, drug metabolism identification experiment using antibody inhibitors Data from a Cytochrome P-450 metabolic enzyme identification experiment using human liver microsomes that have been characterized for Cytochrome P-450 activity and antibodies as specific inhibitors Material from a Cytochrome P-450 metabolic enzyme identification experiment using human liver microsomes that have been characterized for Cytochrome P-450 activity and antibodies as specific inhibitors A Cytochrome P-450 metabolic enzyme identification experiment using human liver microsomes that have been characterized for Cytochrome P-450 activity and chemical inhibitors A CYP450, human microsome, drug metabolism identification experiment using chemical inhibitors Data from a Cytochrome P-450 metabolic enzyme identification experiment using human liver microsomes that have been characterized for Cytochrome P-450 activity and chemical inhibitors Material from a Cytochrome P-450 metabolic enzyme identification experiment using human liver microsomes that have been characterized for Cytochrome P-450 activity and chemical inhibitors Data from a Cytochrome P-450 metabolic enzyme identification experiment using human liver microsomes that have been characterized for Cytochrome P-450 activity Material from a Cytochrome P-450 metabolic enzyme identification experiment using human liver microsomes that have been characterized for Cytochrome P-450 activity A Cytochrome P450 metabolic enzyme identification experiment using recombinant human enzymes A CYP450, recombinant, drug metabolism identification experiment with possibly NO probe enzyme inhibitor(s) A Cytochrome P-450 metabolic enzyme identification experiment using recombinant human enzymes and antibodies as specific inhibitors A CYP450, recombinant, drug metabolism identification experiment using antibody inhibitors Data from a Cytochrome P-450 metabolic enzyme identification experiment using recombinant human enzymes and antibodies as specific inhibitors Material from a Cytochrome P-450 metabolic enzyme identification experiment using recombinant human enzymes and antibodies as specific inhibitors A Cytochrome P-450 metabolic enzyme identification experiment using recombinant human enzymes and chemical inhibitors A CYP450, recombinant, drug metabolism identification experiment using chemical inhibitors Data from a Cytochrome P-450 metabolic enzyme identification experiment using recombinant human enzymes and chemical inhibitors Material from a Cytochrome P-450 metabolic enzyme identification experiment using recombinant human enzymes and chemical inhibitors Data from a Cytochrome P450 metabolic enzyme identification experiment using recombinant human enzymes Material from a Cytochrome P450 metabolic enzyme identification experiment using recombinant human enzymes Material from a metabolic enzyme identification experiment specifically designed to identify the Cytochrome P-450 enzymes involved in the metabolism of a drug Data from a drug metabolism identification experiment -- an experiment conducted with biological tissues and/or chemical compounds in a laboratory designed to "...identify the specific enzymes responsible for the metabolism of a drug'' (fda2006a, p. 25) Material from a drug metabolism identification experiment -- an experiment conducted with biological tissues and/or chemical compounds in a laboratory designed to "...identify the specific enzymes responsible for the metabolism of a drug'' (fda2006a, p. 25) An experiment conducted with biological tissues and/or chemical compounds in a laboratory designed to determine whether or not a drug inhibits a specific drug-metabolizing enzyme A metabolic enzyme inhibition experiment A metabolic \textbf{inhibition} experiment specifically designed to determine whether or not a drug inhibits a specific CYP450 enzyme A CYP450 metabolic enzyme inhibition experiment Data from a metabolic inhibition experiment specifically designed to determine whether or not a drug inhibits a specific CYP450 enzyme A Cytochrome P-450 metabolic enzyme inhibition experiment using human liver microsomes that have been characterized for Cytochrome P-450 activity A CYP450, human microsome, metabolic enzyme inhibition experiment Data from a cytochrome P-450 metabolic enzyme inhibition experiment using human liver microsomes that have been characterized for Cytochrome P-450 activity Material from a cytochrome P-450 metabolic enzyme inhibition experiment using human liver microsomes that have been characterized for Cytochrome P-450 activity A Cytochrome P-450 inhibition experiment using recombinant human enzymes A CYP450, recombinant, metabolic enzyme inhibition experiment Data from a cytochrome P-450 inhibition experiment using recombinant human enzymes Material from a cytochrome P-450 inhibition experiment using recombinant human enzymes Material from a metabolic inhibition experiment specifically designed to determine whether or not a drug inhibits a specific CYP450 enzyme Data from an experiment conducted with biological tissues and/or chemical compounds in a laboratory designed to determine whether or not a drug inhibits a specific drug-metabolizing enzyme Material from an experiment conducted with biological tissues and/or chemical compounds in a laboratory designed to determine whether or not a drug inhibits a specific drug-metabolizing enzyme A statement that does not explicitly refer to evidence items in justification of its assertion(s) A non-traceable, but possibly authoritative, statement "Studies used to test etiologic hypotheses in which inferences about an exposure to putative causal factors are derived from data relating to characteristics of persons under study or to events or experiences in their past. The essential feature is that some of the persons under study have the disease or outcome of interest and their characteristics are compared with those of unaffected persons." MeSH 2007 - D012189 An observational study Data from observational studies, which are defined as: "Studies used to test etiologic hypotheses in which inferences about an exposure to putative causal factors are derived from data relating to characteristics of persons under study or to events or experiences in their past. The essential feature is that some of the persons under study have the disease or outcome of interest and their characteristics are compared with those of unaffected persons." MeSH 2007 - D012189 Material from observational studies, which are defined as: "Studies used to test etiologic hypotheses in which inferences about an exposure to putative causal factors are derived from data relating to characteristics of persons under study or to events or experiences in their past. The essential feature is that some of the persons under study have the disease or outcome of interest and their characteristics are compared with those of unaffected persons." MeSH 2007 - D012189 A pharmacokinetic study where participants receive a drug either in the presence of a purported precipitant (experimental group) or not (control group) but participants are not randomly assigned to experiment and control groups A non-randomized DDI clinical trial Data from a pharmacokinetic study where participants receive a drug either in the presence of a purported precipitant (experimental group) or not (control group) but participants are not randomly assigned to experiment and control groups Material from a pharmacokinetic study where participants receive a drug either in the presence of a purported precipitant (experimental group) or not (control group) but participants are not randomly assigned to experiment and control groups A retrospective study looking at the change in patient exposure of a single drug in the presence of a purported precipitant using a retrospective set of clinical records An observational DDI study Data from a retrospective study looking at the change in patient exposure of a single drug in the presence of a purported precipitant using a retrospective set of clinical records Material from a retrospective study looking at the change in patient exposure of a single drug in the presence of a purported precipitant using a retrospective set of clinical records A pharmacokinetic study involving two groups of non-randomized participants where both groups recieve the purported object drug while only one group receives the purported precipitant A parallel groups DDI clinical trial Data from a pharmacokinetic study involving two groups of non-randomized participants where both groups recieve the purported object drug while only one group receives the purported precipitant Material from a pharmacokinetic study involving two groups of non-randomized participants where both groups recieve the purported object drug while only one group receives the purported precipitant A randomized, controlled, pharmacokinetic study where participants receive a drug wither in the presence of a purported precipitant (experimental group) or not (control group) A randomized DDI clinical trial Data from a randomized, controlled, pharmacokinetic study where participants receive a drug wither in the presence of a purported precipitant (experimental group) or not (control group) Material from a randomized, controlled, pharmacokinetic study where participants receive a drug wither in the presence of a purported precipitant (experimental group) or not (control group) a ``...study of the sources and correlates of variability in drug concentrations among individuals who are the target patient population receiving clinically relevant doses of a drug in question.'' (\cite{fda1999b}, p.1) An observational population PK study Data from a "...study of the sources and correlates of variability in drug concentrations among individuals who are the target patient population receiving clinically relevant doses of a drug in question.'' (fda1999b, p.1) Material from a "...study of the sources and correlates of variability in drug concentrations among individuals who are the target patient population receiving clinically relevant doses of a drug in question.'' (fda1999b, p.1) A published analysis of the evidence supportin and/or refuting some topic A review article "a message that is stated or declared; a communication (oral or written) setting forth particulars or facts etc" Wordnet v2.1 A statement A statement that provides citation to evidence support for justification of its assertion(s) A traceable statement A physical entity "...that catalyzes a particular chemical reaction involving a specific substrate or small number of related substrates" \cite{lodish2004} a kind of evidence where evidence is defined as an artifact that is "...the basis for belief or disbelief; knowledge on which to base belief" see "evidence" in Wordnet 2.1 a kind of data from a specific type of evidence where data is defined as an artifact that is "an item of factual information derived from measurement or research" see "data" in Wordnet 3.1 a kind of material from a specific type of evidence where a material is defined as an artifact that is "things needed for doing or making something" see "material" in Wordnet 3.1 Increased area under the plot of plasma concentration of a drug against time after drug administration. NCI C54605 NCI C54355 (2006) Definition: A control interaction in which a physical entity improves the ability of an enzyme to catalyze an interaction. Definition: A control interaction in which a physical entity reduces the ability of an enzyme to catalyze an interaction. a periodical dedicated to a particular subject whose contents are reviewed by persons considered experts on the subject "Processes that cause many of the chemical changes in living organisms, including anabolism and catabolism. Metabolic processes typically transform small molecules, but also include macromolecular processes such as DNA repair and replication, and protein synthesis and degradation." GO:0008152 'metabolism' "Any of the small, heterogeneous, artifactual, vesicular particles, 50-150 nm in diameter, that are formed when some eukaryotic cells are homogenized and that sediment on centrifugation at 100000 g." GO:0005792 A non-randomized tratment assignment method An assessment tool for grading the validity of an observation-based report's claims A DDI that occurs via a pharmacokinetic mechanism The consequences resulted from pharmacodynamic interactions between the drug and another drug or food. The consequences resulted from pharmacokinetic interactions between the drug and another drug or food. NCI C54354 (2006) A physiological process that moves molecular entities (e.g. drugs) within biological systems -- absorption, distribution, binding, elimination, biotransformation, and excretion A database that receives and stores reports of events of public health interest from various persons and makes these reports accessible to the general public A randomized treatment assignment method A system of proteins "produced by genes or recombinant DNA that has been artificially engineered and inserted into a heterologous host. Recombinant proteins are used extensively by investigators of disease pathways to identify proteintargets for potential drug therapies." Adapted from NCI C17081 'Recombinant_Protein' Method for assigning clinical trial participants to treatment and control groups "The chemical reactions and pathways involving a xenobiotic compound, a compound foreign to living organisms. Used of chemical compounds, e.g. a xenobiotic chemical, such as a pesticide." GO:0006805 A source of proteins that are used in biological experimentation Definition : An entity feature that represent the bound state of a physical entity. A pair of binding features represents a bond. Rationale: A physical entity in a molecular complex is considered as a new state of an entity as it is structurally and functionally different. Binding features provide facilities for describing these states. Similar to other features, a molecule can have bound and not-bound states. Usage: Typically, binding features are present in pairs, each describing the binding characteristic for one of the interacting physical entities. One exception is using a binding feature with no paired feature to describe any potential binding. For example, an unbound receptor can be described by using a "not-feature" property with an unpaired binding feature as its value. BindingSiteType and featureLocation allows annotating the binding location. IntraMolecular property should be set to "true" if the bond links two parts of the same molecule. A pair of binding features are still used where they are owned by the same physical entity. If the binding is due to the covalent interactions, for example in the case of lipoproteins, CovalentBindingFeature subclass should be used instead of this class. Definition: The biological source (organism, tissue or cell type) of an Entity. Usage: Some entities are considered source-neutral (e.g. small molecules), and the biological source of others can be deduced from their constituentss (e.g. complex, pathway). Instances: HeLa cells, Homo sapiens, and mouse liver tissue. Definition: Imposes ordering on a step in a biochemical pathway. Retionale: A biochemical reaction can be reversible by itself, but can be physiologically directed in the context of a pathway, for instance due to flux of reactants and products. Usage: Only one conversion interaction can be ordered at a time, but multiple catalysis or modulation instances can be part of one step. Definition: A conversion in which molecules of one or more physicalEntity pools, undergo covalent modifications and become a member of one or more other physicalEntity pools. The substrates of biochemical reactions are defined in terms of sums of species. This is a convention in biochemistry, and, in principle, all EC reactions should be biochemical reactions. Examples: ATP + H2O = ADP + Pi Comment: In the example reaction above, ATP is considered to be an equilibrium mixture of several species, namely ATP4-, HATP3-, H2ATP2-, MgATP2-, MgHATP-, and Mg2ATP. Additional species may also need to be considered if other ions (e.g. Ca2+) that bind ATP are present. Similar considerations apply to ADP and to inorganic phosphate (Pi). When writing biochemical reactions, it is not necessary to attach charges to the biochemical reactants or to include ions such as H+ and Mg2+ in the equation. The reaction is written in the direction specified by the EC nomenclature system, if applicable, regardless of the physiological direction(s) in which the reaction proceeds. Polymerization reactions involving large polymers whose structure is not explicitly captured should generally be represented as unbalanced reactions in which the monomer is consumed but the polymer remains unchanged, e.g. glycogen + glucose = glycogen. A better coverage for polymerization will be developed. Definition: An conversion in which molecules of one or more physicalEntity pools undergo covalent modifications and become a member of one or more other physicalEntity pools. The substrates of biochemical reactions are defined in terms of sums of species. This is convention in biochemistry, and, in principle, all of the EC reactions should be biochemical reactions. Examples: ATP + H2O = ADP + Pi Comment: In the example reaction above, ATP is considered to be an equilibrium mixture of several species, namely ATP4-, HATP3-, H2ATP2-, MgATP2-, MgHATP-, and Mg2ATP. Additional species may also need to be considered if other ions (e.g. Ca2+) that bind ATP are present. Similar considerations apply to ADP and to inorganic phosphate (Pi). When writing biochemical reactions, it is not necessary to attach charges to the biochemical reactants or to include ions such as H+ and Mg2+ in the equation. The reaction is written in the direction specified by the EC nomenclature system, if applicable, regardless of the physiological direction(s) in which the reaction proceeds. Polymerization reactions involving large polymers whose structure is not explicitly captured should generally be represented as unbalanced reactions in which the monomer is consumed but the polymer remains unchanged, e.g. glycogen + glucose = glycogen. A better coverage for polymerization is currently being developed. ACTIVATION Definition: A control interaction in which a physical entity (a catalyst) increases the rate of a conversion interaction by lowering its activation energy. Instances of this class describe a pairing between a catalyzing entity and a catalyzed conversion. Rationale: Catalysis, theoretically, is always bidirectional since it acts by lowering the activation energy. Physiologically, however, it can have a direction because of the concentration of the participants. For example the oxidative decarboxylation catalyzed by Isocitrate dehydrogenase always happens in one direction under physiological conditions since the produced carbon dioxide is constantly removed from the system. Usage: A separate catalysis instance should be created for each different conversion that a physicalEntity may catalyze and for each different physicalEntity that may catalyze a conversion. For example, a bifunctional enzyme that catalyzes two different biochemical reactions would be linked to each of those biochemical reactions by two separate instances of the catalysis class. Also, catalysis reactions from multiple different organisms could be linked to the same generic biochemical reaction (a biochemical reaction is generic if it only includes small molecules). Generally, the enzyme catalyzing a conversion is known and the use of this class is obvious. In the cases where a catalyzed reaction is known to occur but the enzyme is not known, a catalysis instance can be created without a controller specified. Synonyms: facilitation, acceleration. Examples: The catalysis of a biochemical reaction by an enzyme, the enabling of a transport interaction by a membrane pore complex, and the facilitation of a complex assembly by a scaffold protein. Hexokinase -> (The "Glucose + ATP -> Glucose-6-phosphate +ADP" reaction). A plasma membrane Na+/K+ ATPase is an active transporter (antiport pump) using the energy of ATP to pump Na+ out of the cell and K+ in. Na+ from cytoplasm to extracellular space would be described in a transport instance. K+ from extracellular space to cytoplasm would be described in a transport instance. The ATPase pump would be stored in a catalysis instance controlling each of the above transport instances. A biochemical reaction that does not occur by itself under physiological conditions, but has been observed to occur in the presence of cell extract, likely via one or more unknown enzymes present in the extract, would be stored in the CONTROLLED property, with the CONTROLLER property empty. Definition: A control interaction in which a physical entity (a catalyst) increases the rate of a conversion interaction by lowering its activation energy. Instances of this class describe a pairing between a catalyzing entity and a catalyzed conversion. Rationale: Catalysis, theoretically, is always bidirectional since it acts by lowering the activation energy. Physiologically, however, it can have a direction because of the concentration of the participants. For example, the oxidative decarboxylation catalyzed by Isocitrate dehydrogenase always happens in one direction under physiological conditions since the produced carbon dioxide is constantly removed from the system. Usage: A separate catalysis instance should be created for each different conversion that a physicalEntity may catalyze and for each different physicalEntity that may catalyze a conversion. For example, a bifunctional enzyme that catalyzes two different biochemical reactions would be linked to each of those biochemical reactions by two separate instances of the catalysis class. Also, catalysis reactions from multiple different organisms could be linked to the same generic biochemical reaction (a biochemical reaction is generic if it only includes small molecules). Generally, the enzyme catalyzing a conversion is known and the use of this class is obvious, however, in the cases where a catalyzed reaction is known to occur but the enzyme is not known, a catalysis instance can be created without a controller specified. Synonyms: facilitation, acceleration. Examples: The catalysis of a biochemical reaction by an enzyme, the enabling of a transport interaction by a membrane pore complex, and the facilitation of a complex assembly by a scaffold protein. Hexokinase -> (The "Glucose + ATP -> Glucose-6-phosphate +ADP" reaction). A plasma membrane Na+/K+ ATPase is an active transporter (antiport pump) using the energy of ATP to pump Na+ out of the cell and K+ in. Na+ from cytoplasm to extracellular space would be described in a transport instance. K+ from extracellular space to cytoplasm would be described in a transport instance. The ATPase pump would be stored in a catalysis instance controlling each of the above transport instances. A biochemical reaction that does not occur by itself under physiological conditions, but has been observed to occur in the presence of cell extract, likely via one or more unknown enzymes present in the extract, would be stored in the CONTROLLED property, with the CONTROLLER property empty. 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 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 Definition: The chemical structure of a small molecule. Usage: Structure information is stored in the property STRUCTURE-DATA, in one of three formats: the CML format (see URL www.xml-cml.org), the SMILES format (see URL www.daylight.com/dayhtml/smiles/) or the InChI format (http://www.iupac.org/inchi/). The STRUCTURE-FORMAT property specifies which format is used. Examples: The following SMILES string describes the structure of glucose-6-phosphate: 'C(OP(=O)(O)O)[CH]1([CH](O)[CH](O)[CH](O)[CH](O)O1)'. Definition: The chemical structure of a small molecule. Usage: Structure information is stored in the property structureData, in one of three formats: the CML format (see www.xml-cml.org), the SMILES format (see www.daylight.com/dayhtml/smiles/) or the InChI format (http://www.iupac.org/inchi/). The structureFormat property specifies which format is used. Examples: The following SMILES string describes the structure of glucose-6-phosphate: 'C(OP(=O)(O)O)[CH]1([CH](O)[CH](O)[CH](O)[CH](O)O1)'. 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. Definition: A physical entity whose structure is comprised of other physical entities bound to each other covalently or non-covalently, at least one of which is a macromolecule (e.g. protein, DNA, or RNA). Comment: Complexes must be stable enough to function as a biological unit; in general, the temporary association of an enzyme with its substrate(s) should not be considered or represented as a complex. A complex is the physical product of an interaction (complexAssembly) and is not itself considered an interaction. The boundaries on the size of complexes described by this class are not defined here, although elements of the cell as large and dynamic as, e.g., a mitochondrion would typically not be described using this class (later versions of this ontology may include a cellularComponent class to represent these). The strength of binding cannot be described currently, but may be included in future versions of the ontology, depending on community need. Examples: Ribosome, RNA polymerase II. Other examples of this class include complexes of multiple protein monomers and complexes of proteins and small molecules. Definition: A conversion in which a set of physical entities, at least one being a macromolecule (e.g. protein, RNA, DNA), aggregate. This modification is captured via BindingFeature class. One of the participants of a complexAssembly must be an instance of the class Complex. Usage: This class is also used to represent complex disassembly. The assembly or disassembly of a complex is often a spontaneous process, in which case the direction of the complexAssembly (toward either assembly or disassembly) should be specified via the SPONTANEOUS property. Conversions in which participants obtain or lose CovalentBindingFeatures ( e.g. glycolysation of proteins) should be modeled with BiochemicalReaction. Synonyms: aggregation, complex formation Examples: Assembly of the TFB2 and TFB3 proteins into the TFIIH complex, and assembly of the ribosome through aggregation of its subunits. Definition: A conversion interaction in which a set of physical entities, at least one being a macromolecule (e.g. protein, RNA, DNA), aggregate to from a complex physicalEntity. One of the participants of a complexAssembly must be an instance of the class Complex. The modification of the physicalentities involved in the ComplexAssembly is captured via BindingFeature class. Usage: This class is also used to represent complex disassembly. The assembly or disassembly of a complex is often a spontaneous process, in which case the direction of the complexAssembly (toward either assembly or disassembly) should be specified via the SPONTANEOUS property. Conversions in which participants obtain or lose CovalentBindingFeatures ( e.g. glycolysation of proteins) should be modeled with BiochemicalReaction. Synonyms: aggregation, complex formation Examples: Assembly of the TFB2 and TFB3 proteins into the TFIIH complex, and assembly of the ribosome through aggregation of its subunits. Definition: An interaction in which one entity regulates, modifies, or otherwise influences a continuant entity, i.e. pathway or interaction. Usage: Conceptually, physical entities are involved in interactions (or events) and the events are controlled or modified, not the physical entities themselves. For example, a kinase activating a protein is a frequent event in signaling pathways and is usually represented as an 'activation' arrow from the kinase to the substrate in signaling diagrams. This is an abstraction, called "Activity Flow" representation, that can be ambiguous without context. In BioPAX, this information should be captured as the kinase catalyzing (via an instance of the catalysis class) a Biochemical Reaction in which the substrate is phosphorylated. Subclasses of control define types specific to the biological process that is being controlled and should be used instead of the generic "control" class when applicable. A control can potentially have multiple controllers. This acts as a logical AND, i.e. both controllers are needed to regulate the controlled event. Alternatively multiple controllers can control the same event and this acts as a logical OR, i.e. any one of them is sufficient to regulate the controlled event. Using this structure it is possible to describe arbitrary control logic using BioPAX. Rationale: Control can be temporally non-atomic, for example a pathway can control another pathway in BioPAX. Synonyms: regulation, mediation Examples: A small molecule that inhibits a pathway by an unknown mechanism. Definition: An interaction in which one entity regulates, modifies, or otherwise influences a continuant entity, i.e. pathway or interaction. Usage: Conceptually, physical entities are involved in interactions (or events) and the events should be controlled or modified, not the physical entities themselves. For example, a kinase activating a protein is a frequent event in signaling pathways and is usually represented as an 'activation' arrow from the kinase to the substrate in signaling diagrams. This is an abstraction, called "Activity Flow" representation, that can be ambiguous without context. In BioPAX, this information should be captured as the kinase catalyzing (via an instance of the catalysis class) a Biochemical Reaction in which the substrate is phosphorylated. Subclasses of control define types specific to the biological process that is being controlled and should be used instead of the generic "control" class when applicable. A control can potentially have multiple controllers. This acts as a logical AND, i.e. both controllers are needed to regulate the controlled event. Alternatively multiple controllers can control the same event and this acts as a logical OR, i.e. any one of them is sufficient to regulate the controlled event. Using this structure it is possible to describe arbitrary control logic using BioPAX. Rationale: Control can be temporally non-atomic, for example a pathway can control another pathway in BioPAX. Synonyms: regulation, mediation Examples: A small molecule that inhibits a pathway by an unknown mechanism. Definition: This class represents a term from an external controlled vocabulary (CV). Rationale: Controlled Vocabularies mark cases where BioPAX delegates the representation of a complex biological phenomena to an external controlled vocabulary development effort such as Gene Ontology. Each subclass of this class represents one such case and often has an associated "Best-Practice" external resource to use. See the documentation of each subclass for more specific information. Correct usage of controlled vocabularies are critical to data exchange and integration. Usage: The individuals belonging to this class must unambiguously refer to the source controlled vocabulary. This can be achieved in two manners: The xref property of this class is restricted to the unification xref class. It must point to the source controlled vocabulary. Alternatively the rdf-id of the member individuals can be set to the designated MIRIAM URN. It is a best practice to do both whenever possible. Although it is possible to use multiple unification xrefs to identify semantically identical terms across alternative controlled vocabularies, this is not a recommended practice as it might lead to maintenance issues as the controlled vocabularies change. There is no recommended use-case for directly instantiating this class. Please use its subclasses instead. Definition: An interaction in which molecules of one or more PhysicalEntity pools are physically transformed and become a member of one or more other PhysicalEntity pools. Rationale: Conversion is Comments: Conversions in BioPAX are stoichiometric and closed world, i.e. it is assumed that all of the participants are listed. Both properties are due to the law of mass conservation. Usage: Subclasses of conversion represent different types of transformation reflected by the properties of different physicalEntity. BiochemicalReactions will change the ModificationFeatures on a PhysicalEntity, Transport will change the Cellular Location and ComplexAssembly will change BindingFeatures. Generic Conversion class should only be used when the modification does not fit into a any of these classes. Example: Opening of a voltage gated channel. Definition: An interaction in which molecules of one or more physicalEntity pools are physically transformed and become a member of one or more other physicalEntity pools. Comments: Conversions in BioPAX are stoichiometric and closed world, i.e. i is assumed that all of the participants are listed. Both properties are due to the law of mass conservation. Usage: Subclasses of conversion represent different types of transformation reflected by different physicalEntity properties. BiochemicalReaction will change the ModificationFeatures on the PhysicalEntity , Transport will change the CellularLocation and ComplexAssembly will change the BindingFeature. Generic Conversion class should only be used when the modification does not fit into one of these classes. Example: Opening of a voltage gated channel. Definition : An entity feature that represent the covalently bound state of a physical entity. Rationale: Most frequent covalent modifications to proteins and DNA, such as phosphorylation and metylation are covered by the ModificationFeature class. In these cases, the added groups are simple and stateless therefore they can be captured by a controlled vocabulary. In other cases, such as ThiS-Thilacyl-disulfide, the covalently linked molecules are best represented as a molecular complex. CovalentBindingFeature should be used to model such covalently linked complexes. Usage: Using this construct, it is possible to represent small molecules as a covalent complex of two other small molecules. The demarcation of small molecules is a general problem and is delegated to small molecule databases.The best practice is not to model using covalent complexes unless at least one of the participants is a protein, DNA or RNA. Examples: disulfide bond UhpC + glc-6P -> Uhpc-glc-6p acetyl-ACP -> decenoyl-ACP charged tRNA LEFT-TO-RIGHT Definition: A conversion in which a pool of macromolecules are degraded into their elementary units. Usage: This conversion always has a direction of left-to-right and is irreversible. Degraded molecules are always represented on the left, degradation products on the right. Comments: Degradation is a complex abstraction over multiple reactions. Although it obeys law of mass conservation and stoichiometric, the products are rarely specified since they are ubiquitous. Example: Degradation of a protein to amino acids. Definition: A conversion in which a pool of macromolecules are degraded into their ubiquitous elementary subunits. Usage: This conversion always has a direction of left-to-right and is irreversible. Degraded molecules are always represented on the left, degradation products on the right. Comments: Degradation is a complex abstraction over multiple reactions. Although it obeys law of mass conservation and stoichiometric, the products are rarely specified since they are ubiquitous. Example: Degradation of a protein to amino acids. 1 Definition: Standard transformed Gibbs energy change for a reaction written in terms of biochemical reactants. Usage: Delta-G is represented as a 5-tuple of delta-G'⁰, temperature, ionic strength , pH, and pMg . A conversion in BioPAX may have multiple Delta-G values, representing different measurements for delta-G'⁰ obtained under the different experimental conditions. 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. Definition: A DNA reference is a grouping of several DNA entities that are common in sequence. Members can differ in celular location, sequence features, SNPs, mutations and bound partners. Comments : Note that this is not a reference gene. Genes are non-physical,stateless continuants. Their physical manifestations can span multiple DNA molecules, sometimes even across chromosomes due to regulatory regions. Similarly a gene is not necessarily made up of deoxyribonucleic acid and can be present in multiple copies ( which are different DNA regions). 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 Definition: A region on a DNA molecule. Usage: DNARegion is not a pool of independent molecules but a subregion on these molecules. As such, every DNARegion has a defining DNA molecule. Examples: Proteing encoding region, promoter Definition: A DNA reference is a grouping of several DNA entities that are common in sequence and genomic position. Members can differ in celular location, sequence features, SNPs, mutations and bound partners. Definition: A DNARegionReference is a grouping of several DNARegion entities that are common in sequence and genomic position. Members can differ in cellular location, sequence features, SNPs, mutations and bound partners. Definition: A discrete biological unit used when describing pathways. Rationale: Entity is the most abstract class for representing components of a pathway. It includes both occurents (interactions and pathways) and continuants (physical entities and genes). Loosely speaking, BioPAX Entity is an atomic scientific statement with an associated source, evidence and references. Usage: There is no recommended use-cases for instantiating this class. Please, use its subclasses instead. Synonyms: element, thing,biological unit, statement, observable. Definition: A discrete biological unit used when describing pathways. Rationale: Entity is the most abstract class for representing interacting elements in a pathway. It includes both occurents (interactions and pathways) and continuants (physical entities and genes). Loosely speaking, BioPAX Entity is an atomic scientific statement with an associated source, evidence and references. Synonyms: element, thing, object, bioentity, statement. Description: A characteristic of a physical entity that can change while the entity still retains its biological identity. Rationale: Two phosphorylated forms of a protein are strictly speaking different chemical molecules. It is, however, standard in biology to treat them as different states of the same entity, where the entity is loosely defined based on sequence. Entity Feature class and its subclassses captures these variable characteristics. A Physical Entity in BioPAX represents a pool of molecules rather than an individual molecule. This is a notion imported from chemistry( See PhysicalEntity). Pools are defined by a set of Entity Features in the sense that a single molecule must have all of the features in the set in order to be considered a member of the pool. Since it is impossible to list and experimentally test all potential features for an entity, features that are not listed in the selection criteria is neglected Pools can also be defined by the converse by specifying features that are known to NOT exist in a specific context. As DNA, RNA and Proteins can be hierarchically organized into families based on sequence homology so can entity features. The memberFeature property allows capturing such hierarchical classifications among entity features. Usage: Subclasses of entity feature describe most common biological instances and should be preferred whenever possible. One common usecase for instantiating entity feature is, for describing active/inactive states of proteins where more specific feature information is not available. Examples: Open/close conformational state of channel proteins, "active"/"inactive" states, excited states of photoreactive groups. Description: A characteristic of a physical entity that can change while the entity still retains its biological identity. Rationale: Two phosphorylated forms of a protein are strictly speaking different chemical molecules. It is, however, standard in biology to treat them as different states of the same entity, where the entity is loosely defined based on sequence. Entity Feature class and its subclassses captures these variable characteristics. A Physical Entity in BioPAX represents a pool of molecules rather than an individual molecule. This is a notion imported from chemistry( See PhysicalEntity). Pools are defined by a set of Entity Features in the sense that a single molecule must have all of the features in the set in order to be considered a member of the pool. Since it is impossible to list and experimentally test all potential features for an entity, features that are not listed in the selection criteria is neglected Pools can also be defined by the converse by specifying features that are known to NOT exist in a specific context. As DNA, RNA and Proteins can be hierarchicaly organized into families based on sequence homology so can entity features. The memberFeature property allows capturing such hierarchical classifications among entity features. Usage: Subclasses of entity feature describe most common biological instances and sholud be preferred whenever possible. One common usecase for instatiating entity feature is, for describing active/inactive states of proteins where more specific feature information is not available. Instances: Open/close conformational state of channel proteins, "active"/"inactive" states, excited states of photoreactive groups. Definition: An entity reference is a grouping of several physical entities across different contexts and molecular states, that share common physical properties and often named and treated as a single entity with multiple states by biologists. Rationale: Many protein, small molecule and gene databases share this point of view, and such a grouping is an important prerequisite for interoperability with those databases. Biologists would often group different pools of molecules in different contexts under the same name. For example cytoplasmic and extracellular calcium have different effects on the cell's behavior, but they are still called calcium. For DNA, RNA and Proteins the grouping is defined based on a wildtype sequence, for small molecules it is defined by the chemical structure. Usage: Entity references store the information common to a set of molecules in various states described in the BioPAX document, including database cross-references. For instance, the P53 protein can be phosphorylated in multiple different ways. Each separate P53 protein (pool) in a phosphorylation state would be represented as a different protein (child of physicalEntity) and all things common to all P53 proteins, including all possible phosphorylation sites, the sequence common to all of them and common references to protein databases containing more information about P53 would be stored in a Entity Reference. Comments: This grouping has three semantic implications: 1. Members of different pools share many physical and biochemical properties. This includes their chemical structure, sequence, organism and set of molecules they react with. They will also share a lot of secondary information such as their names, functional groupings, annotation terms and database identifiers. 2. A small number of transitions seperates these pools. In other words it is relatively easy and frequent for a molecule to transform from one physical entity to another that belong to the same reference entity. For example an extracellular calcium can become cytoplasmic, and p53 can become phosphorylated. However no calcium virtually becomes sodium, or no p53 becomes mdm2. In the former it is the sheer energy barrier of a nuclear reaction, in the latter sheer statistical improbability of synthesizing the same sequence without a template. If one thinks about the biochemical network as molecules transforming into each other, and remove edges that respond to transcription, translation, degradation and covalent modification of small molecules, each remaining component is a reference entity. 3. Some of the pools in the same group can overlap. p53-p@ser15 can overlap with p53-p@thr18. Most of the experiments in molecular biology will only check for one state variable, rarely multiple, and never for the all possible combinations. So almost all statements that refer to the state of the molecule talk about a pool that can overlap with other pools. However no overlaps is possible between molecules of different groups. Definiiton: A reference to a term from a reference entity group ontology. There is no "best-practice" vocabulary for this one. 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’. 1 1 1 Definition: The support for a particular assertion, such as the existence of an interaction or pathway. Usage: At least one of CONFIDENCE, EVIDENCE-CODE, or EXPERIMENTAL-FORM must be instantiated when creating an evidence instance. XREF may reference a publication describing the experimental evidence using a publicationXref or may store a description of the experiment in an experimental description database using a unificationXref (if the referenced experiment is the same) or relationshipXref (if it is not identical, but similar in some way e.g. similar in protocol). Evidence is meant to provide more information than just an xref to the source paper. Examples: A description of a molecular binding assay that was used to detect a protein-protein interaction. 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. 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/ 1 Definition: The form of a physical entity in a particular experiment, as it may be modified for purposes of experimental design. Examples: A His-tagged protein in a binding assay. A protein can be tagged by multiple tags, so can have more than 1 experimental form type terms 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 Definition: An entity feature that represents the resulting physical entity subsequent to a cleavage or degradation event. Usage: Fragment Feature can be used to cover multiple types of modfications to the sequence of the physical entity: 1. A protein with a single cleavage site that converts the protein into two fragments (e.g. pro-insulin converted to insulin and C-peptide). TODO: CV term for sequence fragment? PSI-MI CV term for cleavage site? 2. A protein with two cleavage sites that removes an internal sequence e.g. an intein i.e. ABC -> A 3. Cleavage of a circular sequence e.g. a plasmid. In the case of removal ( e.g. intron) the fragment that is *removed* is specified in the feature location property. In the case of a "cut" (e.g. restriction enzyme cut site) the location of the cut is specified instead. Examples: Insulin Hormone 1 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. Definition: A continuant that encodes information that can be inherited through replication. Rationale: Gene is and abstract continuant that can be best described as a "schema". Gene in BioPAX is a generelization over eukaryotic and prokaryotic genes and used only for genetic interactions. Gene is often confused with DNA and RNA fragments that are physical encoding of the gene. Gene expression regulation makes use of DNA and RNA physical entities. Usage: Gene should only be used for describing GeneticInteractions. 1 1 2 Definition : Genetic interactions between genes occur when two genetic perturbations (e.g. mutations) have a combined phenotypic effect not caused by either perturbation alone. A gene participant in a genetic interaction represents the gene that is perturbed. Genetic interactions are not physical interactions but logical (AND) relationships. Their physical manifestations can be complex and span an arbitarily long duration. Rationale: Currently, BioPAX provides a simple definition that can capture most genetic interactions described in the literature. In the future, if required, the definition can be extended to capture other logical relationships and different, participant specific phenotypes. Example: A synthetic lethal interaction occurs when cell growth is possible without either gene A OR B, but not without both gene A AND B. If you knock out A and B together, the cell will die. Definition : Genetic interactions between genes occur when two genetic perturbations (e.g. mutations) have a combined phenotypic effect not caused by either perturbation alone. A gene participant in a genetic interaction represents the gene that is perturbed. Genetic interactions are not physical interactios but logical (AND) relationships. Their physical manifestations can be complex and span an arbitarily long duration. Rationale: Currently, BioPAX provides a simple definition that can capture most genetic interactions described in the literature. In the future, if required, the definition can be extended to capture other logical relationships and different, participant specific phenotypes. Example: A synthetic lethal interaction occurs when cell growth is possible without either gene A OR B, but not without both gene A AND B. If you knock out A and B together, the cell will die. Definition: A biological relationship between two or more entities. Rationale: BioPAX interactions are atomic from modeling perspective, i.e. it is not possible to define sub-interactions. For representing non-atomic continuants with explicit subevents, pathway class should be used. Interactions does not have to be temporally atomic though, for example genetic interactions cover a large span of time. Usage: Interaction is a highly abstract class and in almost all cases it is more appropriate to use subclasses of interaction. It is partially possible to define generic reactions by using generic participants. A more comprehensive method is planned for BioPAX L4 for covering all generic cases like oxidization of a generic alcohol. Synonyms: Process, relationship, event. Examples: protein-protein interaction, biochemical reaction, enzyme catalysis Definition: A biological relationship between two or more entities. Rationale: In BioPAX, interactions are atomic from a database modeling perspective, i.e. interactions can not be decomposed into sub-interactions. When representing non-atomic continuants with explicit subevents the pathway class should be used instead. Interactions are not necessarily temporally atomic, for example genetic interactions cover a large span of time. Interactions as a formal concept is a continuant, it retains its identitiy regardless of time, or any differences in specific states or properties. Usage: Interaction is a highly abstract class and in almost all cases it is more appropriate to use one of the subclasses of interaction. It is partially possible to define generic reactions by using generic participants. A more comprehensive method is planned for BioPAX L4 for covering all generic cases like oxidization of a generic alcohol. Synonyms: Process, relationship, event. Examples: protein-protein interaction, biochemical reaction, enzyme catalysis 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 1 Definition: The apparent equilibrium constant, K', and associated values. Usage: Concentrations in the equilibrium constant equation refer to the total concentrations of all forms of particular biochemical reactants. For example, in the equilibrium constant equation for the biochemical reaction in which ATP is hydrolyzed to ADP and inorganic phosphate: K' = [ADP][P_i]/[ATP], The concentration of ATP refers to the total concentration of all of the following species: [ATP] = [ATP^4-] + [HATP^3-] + [H₂ATP^2-] + [MgATP^2-] + [MgHATP^-] + [Mg₂ATP]. The apparent equilibrium constant is formally dimensionless, and can be kept so by inclusion of as many of the terms (1 mol/dm³) in the numerator or denominator as necessary. It is a function of temperature (T), ionic strength (I), pH, and pMg (pMg = -log₁₀[Mg²⁺]). Therefore, these quantities must be specified to be precise, and values for KEQ for biochemical reactions may be represented as 5-tuples of the form (K' T I pH pMg). This property may have multiple values, representing different measurements for K' obtained under the different experimental conditions listed in the 5-tuple. (This definition adapted from EcoCyc) See http://www.chem.qmul.ac.uk/iubmb/thermod/ for a thermodynamics tutorial. Definition: An entity feature that represents the covalently modified state of a dna, rna or a protein. Rationale: In Biology, identity of DNA, RNA and Protein entities are defined around a wildtype sequence. Covalent modifications to this basal sequence are represented using modificaton features. Since small molecules are identified based on their chemical structure, not sequence, a covalent modification to a small molecule would result in a different molecule. Usage: The added groups should be simple and stateless, such as phosphate or methyl groups and are captured by the modificationType controlled vocabulary. In other cases, such as covalently linked proteins, use CovalentBindingFeature instead. Instances: A phosphorylation on a protein, a methylation on a DNA. Definition: A control interaction in which a physical entity modulates a catalysis interaction. Biologically, most modulation interactions describe an interaction in which a small molecule alters the ability of an enzyme to catalyze a specific reaction. Instances of this class describe a pairing between a modulating entity and a catalysis interaction. Comment: A separate modulation instance should be created for each different catalysis instance that a physical entity may modulate and for each different physical entity that may modulate a catalysis instance. A typical modulation instance has a small molecule as the controller entity and a catalysis instance as the controlled entity. Examples: Allosteric activation and competitive inhibition of an enzyme's ability to catalyze a specific reaction. Definition: A control interaction in which a physical entity modulates a catalysis interaction. Rationale: Biologically, most modulation interactions describe an interaction in which a small molecule alters the ability of an enzyme to catalyze a specific reaction. Instances of this class describe a pairing between a modulating entity and a catalysis interaction. Usage: A typical modulation instance has a small molecule as the controller entity and a catalysis instance as the controlled entity. A separate modulation instance should be created for each different catalysis instance that a physical entity may modulate, and for each different physical entity that may modulate a catalysis instance. Examples: Allosteric activation and competitive inhibition of an enzyme's ability to catalyze a specific reaction. Definition: A control interaction in which a physical entity modulates a catalysis interaction. Rationale: Biologically, most modulation interactions describe an interaction in which a small molecule alters the ability of an enzyme to catalyze a specific reaction. Instances of this class describe a pairing between a modulating entity and a catalysis interaction. Usage: A separate modulation instance should be created for each different catalysis instance that a physical entity may modulate and for each different physical entity that may modulate a catalysis instance. A typical modulation instance has a small molecule as the controller entity and a catalysis instance as the controlled entity. Examples: Allosteric activation and competitive inhibition of an enzyme's ability to catalyze a specific reaction. Definition: An interaction in which participants bind physically to each other, directly or indirectly through intermediary molecules. Rationale: There is a large body of interaction data, mostly produced by high throughput systems, that does not satisfy the level of detail required to model them with ComplexAssembly class. Specifically, what is lacking is the stoichiometric information and completeness (closed-world) of participants required to model them as chemical processes. Nevertheless interaction data is extremely useful and can be captured in BioPAX using this class. Usage: This class should be used by default for representing molecular interactions such as those defined by PSI-MI level 2.5. The participants in a molecular interaction should be listed in the PARTICIPANT slot. Note that this is one of the few cases in which the PARTICPANT slot should be directly populated with instances (see comments on the PARTICPANTS property in the interaction class description). If all participants are known with exact stoichiometry, ComplexAssembly class should be used instead. Example: Two proteins observed to interact in a yeast-two-hybrid experiment where there is not enough experimental evidence to suggest that the proteins are forming a complex by themselves without any indirect involvement of other proteins. This is the case for most large-scale yeast two-hybrid screens. Definition: An interaction in which participants bind physically to each other,directly or indirectly through intermediary molecules. Rationale: There is a large body of interaction data, mostly produced by high throughput systems, that does not satisfy the level of detail required to model them with ComplexAssembly class. Specifically, what is lacking is the stoichiometric information and completeness ( closed-world) of participants required to model them as chemical processes. Nevertheless interaction data is extremely useful and can be captured in BioPAX using this class. Usage: This class should be used by default for representing molecular interactions, such as those defined by PSI-MI level 2.5. The participants in a molecular interaction should be listed in the PARTICIPANTS slot. Note that this is one of the few cases in which the PARTICPANT slot should be directly populated with instances (see comments on the PARTICPANTS property in the interaction class description). If all participants are known with exact stoichiometry, ComplexAssembly class should be used instead. Example: Two proteins observed to interact in a yeast-two-hybrid experiment where there is not enough experimental evidence to suggest that the proteins are forming a complex by themselves without any indirect involvement of other proteins. This is the case for most large-scale yeast two-hybrid screens. 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 Definition: A set or series of interactions, often forming a network, which biologists have found useful to group together for organizational, historic, biophysical or other reasons. Usage: Pathways can be used for demarcating any subnetwork of a BioPAX model. It is also possible to define a pathway without specifying the interactions within the pathway. In this case, the pathway instance could consist simply of a name and could be treated as a 'black box'. Pathways can overlap, i.e. a single interaction might belong to multiple pathways. Pathways can also contain sub-pathways. Synonyms: network, module, cascade, Examples: glycolysis, valine biosynthesis, EGFR signaling Definition: A step in an ordered pathway. Rationale: Some pathways can have a temporal order. For example if the pathway boundaries is based on a perturbation phenotype link the pathway might start with the perturbing agent and end at gene expression leading to the observed changes. Pathway steps can represent directed compound graphs. Usage: Multiple interactions may occur in a pathway step, each should be listed in the STEP-INTERACTION property. Order relationships between pathway steps may be established with the NEXT-STEP slot. If the reaction contained in the step is a reversible biochemical reaction but physiologically has a direction in the context of this pathway, use Biochemical Pathway Step instead. Example: A metabolic pathway may contain a pathway step composed of one biochemical reaction (BR1) and one catalysis (CAT1) instance, where CAT1 describes the catalysis of BR1. The M phase of the cell cycle, defined as a pathway, precedes the G1 phase, also defined as a pathway. Definition: A step in an ordered pathway. Rationale: Some pathways can have a temporal order. For example, if the pathway boundaries are based on a perturbation phenotype link, the pathway might start with the perturbing agent and end at gene expression leading to the observed changes. Pathway steps can represent directed compound graphs. Usage: Multiple interactions may occur in a pathway step, each should be listed in the stepProcess property. Order relationships between pathway steps may be established with the nextStep slot. If the reaction contained in the step is a reversible biochemical reaction but physiologically has a direction in the context of this pathway, use the subclass BiochemicalPathwayStep. Example: A metabolic pathway may contain a pathway step composed of one biochemical reaction (BR1) and one catalysis (CAT1) instance, where CAT1 describes the catalysis of BR1. The M phase of the cell cycle, defined as a pathway, precedes the G1 phase, also defined as a pathway. 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. 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. A protein reference is a grouping of several protein entities that are encoded by the same gene. Members can differ in celular location, sequence features and bound partners. Currently conformational states (such as open and closed) are not covered. Description: A protein reference is a grouping of several protein entities that are encoded by the same genetic sequence. Members can differ in any combination of cellular location, sequence features and bound partners. Rationale: Protein molecules, encoded by the same genetic sequence can be present in (combinatorially many) different states, as a result of post translational modifications and non-covalent bonds. Each state, chemically, is a different pool of molecules. They are, however, related to each other because: They all share the same "base" genetic sequence. They can only be converted to each other but not to any other protein Comments:Most Protein databases, including UniProt would map one to one with ProteinReferences in BioPAX. Definition: The direct source of a pathway data or score. Usage: This does not store the trail of sources from the generation of the data to this point, only the last known source, such as a database. The XREF property may contain a publicationXref referencing a publication describing the data source (e.g. a database publication). A unificationXref may be used e.g. when pointing to an entry in a database of databases describing this database. Examples: A database, scoring method or person name. 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. 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 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 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. 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. Defintion: A RNA reference is a grouping of several RNA entities that are either encoded by the same gene or replicates of the same genome. Members can differ in celular location, sequence features and bound partners. Currently conformational states (such as hairpin) are not covered. 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 Definition: A RNA reference is a grouping of several RNA entities that are common in sequence and genomic position. Members can differ in celular location, sequence features, mutations and bound partners. Definition: A RNARegion reference is a grouping of several RNARegion entities that are common in sequence and genomic position. Members can differ in celular location, sequence features, mutations and bound partners. 1 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". Definition: An interval on a sequence. Usage: Interval is defined as an ordered pair of SequenceSites. All of the sequence from the begin site to the end site (inclusive) is described, not any subset. Definition: An interval on a sequence. Usage: Inverval is defined as an ordered pair of SequenceSites. All of the sequence from the begin site to the end site (inclusive) is described, not any subset. Definition: A location on a nucleotide or amino acid sequence. Usage: For most purposes it is more appropriate to use subclasses of this class. Direct instances of SequenceLocation can be used for uknown locations that can not be classified neither as an interval nor a site. 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. 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 Definition: Describes a site on a sequence, i.e. the position of a single nucleotide or amino acid. Usage: A sequence site is always defined based on the reference sequence of the owning entity. For DNARegion and RNARegion it is relative to the region itself not the genome or full RNA molecule. Definition: A pool of molecules that are neither complexes nor are genetically encoded. Rationale: Identity of small molecules are based on structure, rather than sequence as in the case of DNA, RNA or Protein. A small molecule reference is a grouping of several small molecule entities that have the same chemical structure. Usage : Smalle Molecules can have a cellular location and binding features. They can't have modification features as covalent modifications of small molecules are not considered as state changes but treated as different molecules. Some non-genomic macromolecules, such as large complex carbohydrates are currently covered by small molecules despite they lack a static structure. Better coverage for such molecules require representation of generic stoichiometry and polymerization, currently planned for BioPAX level 4. Examples: glucose, penicillin, phosphatidylinositol A small molecule reference is a grouping of several small molecule entities that have the same chemical structure. Members can differ in celular location and bound partners. Covalent modifications of small molecules are not considered as state changes but treated as different molecules. 1 1 1 Definition: Stoichiometric coefficient of a physical entity in the context of a conversion or complex. Usage: For each participating element there must be 0 or 1 stoichiometry element. A non-existing stoichiometric element is treated as unknown. This is an n-ary bridge for left, right and component properties. Relative stoichiometries ( e.g n, n+1) often used for describin polymerization is not supported. Definition: Stoichiometric coefficient of a physical entity in the context of a conversion or complex. Usage: For each participating element there must be 0 or 1 stoichiometry element. A non-existing stoichiometric element is treated as unknown. This is an n-ary bridge for left, right and component properties. Relative stoichiometries ( e.g n, n+1) often used for describing polymerization is not supported. Definiton: An interaction where a macromolecule is polymerized from a template macromolecule. Rationale: This is an abstraction over multiple (not explicitly stated) biochemical reactions. The ubiquitous molecules (NTP and amino acids) consumed are also usually omitted. Template reaction is non-stoichiometric, does not obey law of mass conservation and temporally non-atomic. It, however, provides a mechanism to capture processes that are central to all living organisms. Usage: Regulation of TemplateReaction, e.g. via a transcription factor can be captured using TemplateReactionRegulation. TemplateReaction can also be indirect for example, it is not necessary to represent intermediary mRNA for describing expression of a protein. It was decided to not subclass TemplateReaction to subtypes such as transcription of translation for the sake of simplicity. If needed these subclasses can be added in the future. Examples: Transcription, translation, replication, reverse transcription. E.g. DNA to RNA is transcription, RNA to protein is translation and DNA to protein is protein expression from DNA. Definiton: An interaction where a macromolecule is polymerized from a template macromolecule. Rationale: This is an abstraction over multiple (omitted) biochemical reactions. Ubiquitous molecules ( NTP and amino acids) consumed are also omitted. Template reaction is non-stoichiometric, does not obey law of mass conservation and temporally non-atomic. It, however, provides a mechanism to capture processes that are central to all living organisms. Usage: Regulation of TemplateReaction, e.g. via a transcription factor can be captured using TemplateReactionRegulation. TemplateReaction can also be indirect, for example it is not necessary to represent intermediary mRNA for describing expression of a protein. It was decided to not subclass TemplateReaction to subtypes such as transcription of translation for the sake of simplicity. If needed these subclasses can be added in the future. Examples: Transcription, translation, replication, reverse transcription. E.g. DNA to RNA is transcription, RNA to protein is translation and DNA to protein is protein expression from DNA. ACTIVATION INHIBITION Definition: Regulation of an expression reaction by a controlling element such as a transcription factor or microRNA. Usage: To represent the binding of the transcription factor to a regulatory element in the TemplateReaction, create a complex of the transcription factor and the regulatory element and set that as the controller. Definition: Regulation of the expression reaction by the controlling element such as a transcription factor or microRNA. E.g. To represent the binding of the transcription factor to a regulatory element in the TemplateReaction, create a complex of the transcription factor and the regulatory element and set that as the controller. 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 Definition: An conversion in which molecules of one or more physicalEntity pools change their subcellular location and become a member of one or more other physicalEntity pools. A transport interaction does not include the transporter entity, even if one is required in order for the transport to occur. Instead, transporters are linked to transport interactions via the catalysis class. Usage: If there is a simultaneous chemical modification of the participant(s), use transportWithBiochemicalReaction class. Synonyms: translocation. Examples: The movement of Na+ into the cell through an open voltage-gated channel. Definition: A conversion interaction that is both a biochemicalReaction and a transport. In transportWithBiochemicalReaction interactions, one or more of the substrates change both their location and their physical structure. Active transport reactions that use ATP as an energy source fall under this category, even if the only covalent change is the hydrolysis of ATP to ADP. Rationale: This class was added to support a large number of transport events in pathway databases that have a biochemical reaction during the transport process. It is not expected that other double inheritance subclasses will be added to the ontology at the same level as this class. Examples: In the PEP-dependent phosphotransferase system, transportation of sugar into an E. coli cell is accompanied by the sugar's phosphorylation as it crosses the plasma membrane. Definition: A conversion interaction that is both a biochemicalReaction and a transport. In transportWithBiochemicalReaction interactions, one or more of the substrates changes both their location and their physical structure. Active transport reactions that use ATP as an energy source fall under this category, even if the only covalent change is the hydrolysis of ATP to ADP. Rationale: This class was added to support a large number of transport events in pathway databases that have a biochemical reaction during the transport process. It is not expected that other double inheritance subclasses will be added to the ontology at the same level as this class. Examples: In the PEP-dependent phosphotransferase system, transportation of sugar into an E. coli cell is accompanied by the sugar's phosphorylation as it crosses the plasma membrane. 1 1 Definition: A unification xref defines a reference to an entity in an external resource that has the same biological identity as the referring entity Rationale: Unification xrefs are critically important for data integration. In the future they can be replaced by direct miriam links and rdf:id based identity management. Usage: For example, if one wished to link from a database record, C, describing a chemical compound in a BioPAX data collection to a record, C', describing the same chemical compound in an external database, one would use a unification xref since records C and C' describe the same biological identity. Generally, unification xrefs should be used whenever possible, although there are cases where they might not be useful, such as application to application data exchange.Identity of interactions can be computed based on the identity of its participants. An xref in a protein pointing to a gene, e.g. in the LocusLink database17, would not be a unification xref since the two entities do not have the same biological identity (one is a protein, the other is a gene). Instead, this link should be a captured as a relationship xref. References to an external controlled vocabulary term within the OpenControlledVocabulary class should use a unification xref where possible (e.g. GO:0005737). Examples: An xref in a protein instance pointing to an entry in the Swiss-Prot database, and an xref in an RNA instance pointing to the corresponding RNA sequence in the RefSeq database.. 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.. Definition: This is a placeholder for classes, used for annotating the "Entity" and its subclasses but are not an "Entity" themselves. Examples include references to external databases, controlled vocabularies, evidence and provenance. Rationale: Utility classes are created when simple slots are insufficient to describe an aspect of an entity or to increase compatibility of this ontology with other standards. Usage: The utilityClass class is actually a metaclass and is only present to organize the other helper classes under one class hierarchy; instances of utilityClass should never be created. 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. The FDA's Adverse Event Reporting System: http://www.fda.gov/cder/aers/default.htm A pharmacokinetic clinical trial study design involving two groups of non-randomized participants where both groups recieve the purported object drug while only one group receives the purported precipitant The US Food and Drug Administration (FDA): http://www.fda.gov/opacom/hpview.html human liver microsomes recombinant human cytochrome P450 isoenzymes "A derivative of LOVASTATIN and potent competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HYDROXYMETHYLGLUTARYL COA REDUCTASES), which is the rate-limiting enzyme in cholesterol biosynthesis. It may also interfere with steroid hormone production. Due to the induction of hepatic LDL RECEPTORS, it increases breakdown of LDL-cholesterol (LIPOPROTEINS, LDL CHOLESTEROL)." (MeSH D019821) C22028 VA_NDFRT Definition: A pool of molecules or molecular complexes. Comments: Each PhysicalEntity is defined by a sequence or structure based EntityReference AND a set of Features. For example, ser46 phosphorylated p53 is a physical entity in BioPAX defined by the p53 sequence and the phosphorylation feature. Features are any combination of cellular location, covalent and non-covalent bonds with other molecules and covalent modifications. For a specific molecule to be a member of the pool it has to satisfy all of the specified features. Unspecified features are treated as don't care. Features that should not be on the molecules should be explicitly stated with "not feature" property. A physical entity in BioPAX never represents a specific molecular instance. Physical Entity can be heterogenous and potentially overlap, i.e. a single molecule can be counted as a member of multiple pools. This makes BioPAX semantics different than regular chemical notation but is necessary for dealing with combinatorial complexity. Synonyms: part, interactor, object, species Examples: extracellular calcium, ser 64 phosphorylated p53 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 The physical entity to be annotated with stoichiometry. Coverage Coverage will typically include spatial location (a place name or geographic coordinates), temporal period (a period label, date, or date range) or jurisdiction (such as a named administrative entity). Recommended best practice is to select a value from a controlled vocabulary (for example, the Thesaurus of Geographic Names [TGN]) and that, where appropriate, named places or time periods be used in preference to numeric identifiers such as sets of coordinates or date ranges. The extent or scope of the content of the resource. Subject and Keywords The topic of the content of the resource. Typically, a Subject will be expressed as keywords, key phrases or classification codes that describe a topic of the resource. Recommended best practice is to select a value from a controlled vocabulary or formal classification scheme. Resource Type The nature or genre of the content of the resource. Type includes terms describing general categories, functions, genres, or aggregation levels for content. Recommended best practice is to select a value from a controlled vocabulary (for example, the DCMI Type Vocabulary [DCMITYPE]). To describe the physical or digital manifestation of the resource, use the Format element. Resource Identifier An unambiguous reference to the resource within a given context. Recommended best practice is to identify the resource by means of a string or number conforming to a formal identification system. Example formal identification systems include the Uniform Resource Identifier (URI) (including the Uniform Resource Locator (URL)), the Digital Object Identifier (DOI) and the International Standard Book Number (ISBN). 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. Values of this property define external cross-references from this entity to entities in external databases. double blind crossover design double blind crossover designs double blind crossover studies double blind crossover study double blind crossover trial double blind crossover trials double-blind crossover design double-blind crossover designs double-blind crossover studies double-blind crossover study double-blind crossover trial double-blind crossover trials Ashleigh Faith Research Activity D004311 Research design [1977-1989] Relation Recommended best practice is to reference the resource by means of a string or number conforming to a formal identification system. A reference to a related resource. Rights Management Typically, a Rights element will contain a rights management statement for the resource, or reference a service providing such information. Rights information often encompasses Intellectual Property Rights (IPR), Copyright, and various Property Rights. If the Rights element is absent, no assumptions can be made about the status of these and other rights with respect to the resource. Information about rights held in and over the resource. literature review review, academic review of literature D016454 reviews review literature review An article or book published after examination of published material on a subject. It may be comprehensive to various degrees and the time range of material scrutinized may be broad or narrow, but the reviews most often desired are reviews of the current literature. The textual material examined may be equally broad and can encompass, in medicine specifically, clinical material as well as experimental research or case reports. State-of-the-art reviews tend to address more current matters. [MeSH_2014] literature reviews review, multicase review of reported cases Ashleigh Faith Intellectual Product Significant review of original research. [Emtree_2014] randomized clinical trial randomised clinical design randomised clinical designs randomised clinical studies randomised clinical study randomised clinical trial randomised clinical trials randomized clinical design randomized clinical designs randomized clinical studies randomized clinical study randomized clinical trials C0206034 Ashleigh Faith Research Activity A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial. [NCIT_14.05d] Used as a drug subheading when the clinical trial of a drug is reported. [Clinical trial | Embase_2014] C15417 Used for original reports of prospective clinical studies in which the (comparative) efficacy of one or more medical interventions in humans is evaluated; also used for prospective clinical veterinary trials in which the (comparative) efficacy of one or more medical interventions in animals is evaluated. [Clinical trial | Embase_2014] Language A language of the intellectual content of the resource. Recommended best practice is to use RFC 3066 [RFC3066], which, in conjunction with ISO 639 [ISO639], defines two- and three-letter primary language tags with optional subtags. Examples include "en" or "eng" for English, "akk" for Akkadian, and "en-GB" for English used in the United Kingdom.