Changes

A general This tutorial for Protégé (desktop and web-version) can be found at the gives an introduction to using [https://protegewikiwww.stanfordpgx.eduno/wiki/Main_Page Protégé Wikiwebprotege WebProtégé]for curating PGx recommendations.

The best Protégé tool for looking at OWL semantics is the desktop version of Protégé, which is a visual frontdeveloped by Stanford University. And general-end to the OWLAPI. However, for collaborative curation of OWLs it may puropose tutorials can be better to use found at the WebProtege. We [https://wwwprotegewiki.pgxstanford.noedu/webprotege host our own copy of WebProtégéwiki/Main_Page Stanford Protégé Wiki].

When opening an OUS adapted PharmGKB OWL file in WebProtégé for the first time, we are presented to the [[File:Webprotege main screen.png|thumb|Default ''Classes'' tab with the four views ''Class Hierarchy'' (a tree of all class entities of this ontology), ''Class'' (for description and editing of each class entity), ''Comments'' (for chatting with other curators), and ''Project Feed'' (to see changes to the project.):is shown when opening a new OWL file or creating a new OWL ontology]]

[[File:Webprotege main screen.png|frameless|Default view when When opening an PGx guideline in WebProtégé for the first time, we are presented to the ''Classes'' tab, containing four so-called views (frames)* ''Class Hierarchy'' (a new OWL file or creating a new OWL tree of all class entities of this ontology]])* ''Class'' (for description and editing of each class entity)* ''Comments'' (for chatting with other curators)* ''Project Feed'' (to see changes to the project.)

The user interface of WebProtégé can be modified[[File:WebProtege choose view and arrow lowres. We suggest to replace the png|thumb|Add a view ''Project Feed'' with by clicking the three horizontal bars, and chose appropriate view ''OWL Entity Description Editor''. In this way the editor/curator can inspect semantic properties of the class entities that are not shown in the default view. We suggest to remove the ''Project Feed'' in order to make the interface cleaner. The user can modify the interface will appear as she or he pleases. Available views a box that can be browsed by clicking on the three-bar symbol next to the ''Classes'' tab:placed as desired]]

[[File:WebProtege choose view and arrow lowresThe user interface of WebProtégé can be modified.png|frameless|Add a We suggest to replace the view by clicking ''Project Feed'' with the three horizontal bars, and chose appropriate view ''OWL Entity Description Editor''. In this way the editor/curator can inspect semantic properties of the class entities that will appear are not shown in the default view. We suggest to remove the ''Project Feed'' in order to make the interface cleaner. The user can modify the interface as a box that she or he pleases. Available views can be placed as desired]]browsed by clicking on the three-bar symbol next to the ''Classes'' tab.

We suppose that the user has modified the ''Classes'' tab as explained above. We will use the drug voriconazole as an example. We have downloaded the CPIC guideline from the PharmGKB API and converted the PharmGKB JSON-LD file to the OWL format that can be edited in WebProtégé. ===Curation of the functional status of star alleles===[[File:WebProtege user interface func status.png|thumb|Inspection of the gene function element ''Voriconazole CYP2C19: Decreased function'' in the ''Class Hierarchy'' shows which star alleles that have this functional status]] By navigating in the ''Class Hierachy'' view, the curator can e.g. view the class element ''Voriconazole CYP2C19:Decreased function''. (The naming is based on the functional status that is provided by PharmGKB's API, and the drug and gene name is added because functional status is gene specific and possibly drug specific (may be sensible to make functional status independent of drug, cf. Voriconazole Phenotype below). In the definition of the ''Voriconazole CYP2C19:Decreased function'', pay attention to the ''OWL Entity Description Editor'' where we see that the ''Voriconazole CYP2C19:Decreased function'' is equivalent to a gene that has haplotype either CYP2C19*10, CYP2C19*16, CYP2C19*19, CYP2C19*25, CYP2C19*26 or CYP2C19*9. [[File:WebProtege user interface func status discussion.png|thumb|Comments can be added on a per-element basis to highlighted class elements in the Class Hierarchy, and the comment is by default sent by email to all curators.]] Although the Functional Status can be manually modified by the curator, we believe that it is better to edit the Functional Status programmatically, based on the current PharmGKB functional status. By starting a discussion in the ''Comment'' view, suggestions can be included in the next version of the ontology. ===Curation of the ''Phenotype'' of patient diplotypes===CPIC has recommended to use the term Phenotype for the metabolization status, transportation function or presence of a particular trait. Currently, this Phenotype is not a independent entity in the PharmGKB API. This means that for a drug that is affected by two genes, the Phenotype is aggregated for the two genes. We suggest to make a phenotype per gene, and make a recommendation for the combination of phenotypes. If more genes are added later, then it may be easier to expand the guideline. Another reason for modelling phenotypes on a per gene basis is that we want to make a guideline that is not drug-dependent, but rather made for families of drugs for Psychopharmaca or Cancer, and involving very many different genes.  [[File:WebProtege user interface phen.png|thumb|A model of the CPIC Phenotype by combination of pairs of Functional Statuses]] As an example, we see that the phenotype ''Voriconazole CYP2C19:Intermediate Metabolizer'' is either a heterozygote Voriconazole CYP2C19:Increased function/No function or a Voriconazole CYP2C19:No function/Normal function. As for the functional status, we suggest that curators start a discussion if definitions of Phenotypes should be changed. ===Curation of the ''Recommendation''===Finally, the WebProtégé can be used for writing the actual prose of the recommendations. For instance, if the curator wants to translate the CPIC recommendations into another language, in the ''Class'' view, she can enter a property ''Recommendations'', a recommendation text and tagging it with the appropriate language.[[File:WebProtege user interface guideline language.png|thumb|Translating a CPIC recommendation into another language can be achieved by adding a new property Recommendations with a recommendation text and a language (here ''no'')]] ===Downloading the guideline in OWL format===[[File:WebProtege download owl ontology.png|thumb|A new revision of the OWL PGx guideline can be downloded from the ''History'' tab]] One way to download a new revision of the guideline, is to go to the ''History'' tab, click on the revision number that you want to download, and download this as a .zip-file.  ===Try the Pharmacoracle WebProtégé yourself===Either contact us to [https://www.pgx.no/webprotege register a new account at the WebProtégé], and for access to test ontologies or try the Tutorial account:

[[File:WebProtege user interface func status.png|frameless|Inspection of the element ''Voriconazole CYP2C19: Decreased function'' from the Class Hierarchy describing PGx recommendations for the drug Voriconazole]]Tutorial

Although the Functional Status can be manually modified by the curator, we believe that it is better to edit the Functional Status programmatically, based on the current PharmGKB functional status. By starting a discussion in the ''Comment'' view, suggestions can be included in the next version of the ontologypassword:Tutorial2018

[[File:WebProtege user interface func The Tutorial account contains definitions of PGx alleles, PGx variants, functional status discussion.png|frameless|Comments can be added on a per-element basis to highlighted class elements in the Class Hierarchy, phenotype and recommendations for the comment is by default sent by email to all curatorsdrug azathioprine.]]

CPIC has recommended to use the term Phenotype ==Using Desktop Protégé for the metabolization status, transportation function or presence curation of PGx recommendations==Collaborative curation of a particular trait. Currently, this Phenotype is not a independent entity PGx recommendations can quite easily be performed in the PharmGKB API. This means that for a drug that is affected by two genesWebProtégé, the Phenotype is aggregated for the two genes. We suggest to make a phenotype per geneas explained above (of course, and make a recommendation for the combination of phenotypes. If more genes are added lateras with any tool, then it may be easier curators have to expand the guideline. Another usecase is if we want get used to make a guideline that is not drug-dependent, but rather made for families of drugs for Psychopharmaca or Cancer, and involving very many different genesit).

As an exampleHowever, for quality assurance of PGx guideline semantics, we see that still need to use the phenotype ''Voriconazole CYP2C19:Intermediate Metabolizer'' is either a heterozygote Voriconazole CYP2C19:Increased function/No function or desktop version of Protégé<ref>Support for semantic reasoning may be introduced in WebProtege at a Voriconazole CYP2C19:No functionlater stage</Normal function:[[File:WebProtege user interface phenref>.png|frameless|Anticipating inclusion of CPIC definition of phenotypes in the PharmGKB API data, we have modelled the CPIC Phenotype by combining Functional Statuses]]

As for [[File:Protege compare guideline structure.png|thumb|By running the funtional statusreasoner in the Desktop Protégé, we suggest can ensure that curators start a discussion if definitions of Phenotypes should be changed.the OUS guidelines and the CPIC guidelines are sematnically equivalent]]

Finally, the WebProtégé can be used for writing When changing the actual prose semantic structure of the recommendations. For instance, if the curator wants to translate the CPIC recommendations into another languageguidelines, as explained for Phenotype in the ''Class'' viewsection above, she can enter a property ''Recommendations'', a recommendation text and tagging it with we need to be sure that our new guideline structure is equivalent to the language:structure we get from PharmGKB. [[File:WebProtege user interface guideline language.png|frameless|Translating a CPIC recommendation into another language Consistency can be achieved checked automatically in the Desktop Protege by adding running a new property Recommendations with a recommendation text and a language reasoner (here ''no''e.g. keyboard shortcut Ctrl-r)]]. We then see if our structurally different OUS guidelines give the same recommendations as the CPIC guidelines.