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 is developed by Stanford University. And general-puropose tutorials can be found at OWL semantics is the desktop version of [https://protegewiki.stanford.edu/wiki/Main_Page Stanford Protégé, which is a visual front-end to the OWLAPIWiki].

However==User interface of Pharmacoracle's WebProtégé==[[File:Webprotege main screen.png|thumb|Default ''Classes'' tab with views ''Class Hierarchy'', ''Class'', ''Comments'' and ''Project Feed'' is shown when opening a new OWL file or creating a new OWL ontology]] When opening an PGx guideline in WebProtégé for collaborative curation the first time, we are presented to the ''Classes'' tab, containing four so-called views (frames)* ''Class Hierarchy'' (a tree of OWLs it may be better 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 use the WebProtegeproject. We ) [[httpsFile://wwwWebProtege choose view and arrow lowres.png|thumb|Add a view by clicking the three horizontal bars, and chose appropriate view that will appear as a box that can be placed as desired]] The user interface of WebProtégé can be modified.pgxWe suggest to replace the view ''Project Feed'' with the view ''OWL Entity Description Editor''.noIn this way the editor/webprotege host our own copy curator can inspect semantic properties of WebProtégé]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 as she or he pleases. Available views can be browsed by clicking on the three-bar symbol next to the ''Classes'' tab.

==User interface Using WebProtégé for curation of Pharmacoracle's WebProtégéPGx recommendations==When opening We suppose that the user has modified the ''Classes'' tab as explained above. We will use the drug voriconazole as an OUS adapted example. We have downloaded the CPIC guideline from the PharmGKB API and converted the PharmGKB JSON-LD file to the OWL file format that can be edited in WebProtégé for . ===Curation of the first time, we are presented to functional status of star alleles===[[File:WebProtege user interface func status.png|thumb|Inspection of the gene function element ''ClassesVoriconazole CYP2C19: Decreased function'' tab with in the four views ''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.)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 tree of 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 class entities 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 this the ontology), . ===Curation of the ''ClassPhenotype'' (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 description Psychopharmaca or Cancer, and editing involving very many different genes.  [[File:WebProtege user interface phen.png|thumb|A model of each class entity)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 ''CommentsRecommendation'' (===Finally, the WebProtégé can be used for chatting 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 other curatorsa 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 ''Project FeedHistory'' (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 see changes [https://www.pgx.no/webprotege register a new account at the WebProtégé], and for access to test ontologies or try the projectTutorial account: user: Tutorial password: Tutorial2018 The Tutorial account contains definitions of PGx alleles, PGx variants, functional status, phenotype and recommendations for the drug azathioprine. ==Using Desktop Protégé for curation of PGx recommendations==Collaborative curation of PGx recommendations can quite easily be performed in WebProtégé, as explained above (of course, as with any tool, curators have to get used to it):.

[[File:Webprotege main screenHowever, for quality assurance of PGx guideline semantics, we still need to use the desktop version of Protégé<ref>Support for semantic reasoning may be introduced in WebProtege at a later stage</ref>.png|frameless|Default view when opening a new OWL file or creating a new OWL ontology]]

The user interface of WebProtégé can be modified[[File:Protege compare guideline structure. We suggest to replace png|thumb|By running the view ''Project Feed'' with the view ''OWL Entity Description Editor''. In this way reasoner in the editor/curator Desktop Protégé, we can inspect semantic properties of the class entities ensure that are not shown in the default view. We suggest to remove OUS guidelines and the ''Project Feed'' in order to make the interface cleaner. The user can modify the interface as she or he pleases. Available views can be browsed by clicking on the three-bar symbol next to the ''Classes'' tab:CPIC guidelines are sematnically equivalent]]

[[File:WebProtege choose view and arrow lowres.png|frameless|Add a view by clicking When changing the semantic structure of the three horizontal barsguidelines, and chose appropriate view that will appear as a box explained for Phenotype in the section above, we need to be sure that our new guideline structure is equivalent to the structure we get from PharmGKB. Consistency can be placed checked automatically in the Desktop Protege by running a reasoner (e.g. keyboard shortcut Ctrl-r). We then see if our structurally different OUS guidelines give the same recommendations as desired]]the CPIC guidelines.