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].
==User interface of Pharmacoracle's WebProtégé==
[[File:Webprotege main screen.png|thumb|Default view ''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 OUS adapted PharmGKB OWL file PGx guideline in WebProtégé for the first time, we are presented to the ''Classes'' tab, containing four so-called views(frames)
* ''Class Hierarchy'' (a tree of all class entities of this ontology)
* ''Class'' (for description and editing of each class entity)
==Using WebProtégé for curation of PGx recommendations==
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.]]
[[File:WebProtege user interface func 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.png|frameless|Inspection of By starting a discussion in the element ''Voriconazole CYP2C19: Decreased functionComment'' from view, suggestions can be included in the Class Hierarchy describing PGx recommendations for next version of the drug Voriconazole]]ontology.
Although ===Curation of the ''Phenotype'' of patient diplotypes===CPIC has recommended to use the Functional Status can be manually modified by term Phenotype for the curatormetabolization status, transportation function or presence of a particular trait. Currently, we believe this Phenotype is not a independent entity in the PharmGKB API. This means that for a drug that it is better to edit affected by two genes, the Functional Status programmatically, based on Phenotype is aggregated for the current PharmGKB functional statustwo genes. By starting We suggest to make a phenotype per gene, and make a discussion in recommendation for the ''Comment'' viewcombination of phenotypes. If more genes are added later, suggestions can then it may be included in easier to expand the next version 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 the ontology:drugs for Psychopharmaca or Cancer, and involving very many different genes.
[[File:WebProtege user interface func status discussionphen.png|framelessthumb|Comments can be added on a per-element basis to highlighted class elements in A model of the Class Hierarchy, and the comment is CPIC Phenotype by default sent by email to all curators.combination of pairs of Functional Statuses]]
CPIC has recommended to use the term Phenotype for the metabolization statusAs an example, transportation function or presence of a particular trait. Currently, this Phenotype is not a independent entity in the PharmGKB API. This means we see that for a drug that is affected by two genes, the Phenotype phenotype ''Voriconazole CYP2C19:Intermediate Metabolizer'' is aggregated for the two genes. We suggest to make either a phenotype per gene, and make heterozygote Voriconazole CYP2C19:Increased function/No function or a recommendation Voriconazole CYP2C19:No function/Normal function. As for the combination of phenotypes. If more genes are added laterfunctional status, then it may be easier to expand the guideline. Another usecase is if we want to make suggest that curators start a guideline that is not drug-dependent, but rather made for families discussion if definitions of drugs for Psychopharmaca or Cancer, and involving very many different genesPhenotypes should be changed.
As an example===Curation of the ''Recommendation''===Finally, we see that the phenotype 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 ''Voriconazole CYP2C19:Intermediate MetabolizerClass'' is either view, she can enter a heterozygote Voriconazole CYP2C19:Increased function/No function or property ''Recommendations'', a Voriconazole CYP2C19:No function/Normal function:recommendation text and tagging it with the appropriate language.[[File:WebProtege user interface phenguideline language.png|framelessthumb|Anticipating inclusion of CPIC definition of phenotypes in the PharmGKB API data, we have modelled the Translating a CPIC Phenotype recommendation into another language can be achieved by combining Functional Statusesadding a new property Recommendations with a recommendation text and a language (here ''no'')]]
As for ===Downloading the functional status, we suggest that curators start a discussion if definitions guideline in OWL format===[[File:WebProtege download owl ontology.png|thumb|A new revision of Phenotypes should the OWL PGx guideline can be changed.downloded from the ''History'' tab]]
Finally, the WebProtégé can be used for writing the actual prose One way to download a new revision of the recommendations. For instanceguideline, if the curator wants is to go to translate the CPIC recommendations into another language, in the ''ClassHistory'' viewtab, she can enter a property ''Recommendations''click on the revision number that you want to download, and download this as a recommendation text and tagging it with .zip-file. ===Try the language:Pharmacoracle WebProtégé yourself===Either contact us to [[Filehttps:WebProtege user interface guideline language//www.pgx.png|frameless|Translating a CPIC recommendation into another language can be achieved by adding no/webprotege register a new property Recommendations with a recommendation text account at the WebProtégé], and for access to test ontologies or try the Tutorial account: user: Tutorial password: Tutorial2018 The Tutorial account contains definitions of PGx alleles, PGx variants, functional status, phenotype and a language (here ''no'')]]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).
However, 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>.
[[File:Protege compare guideline structure.png|thumb|By running the reasoner in the Desktop Protégé, we can ensure that the OUS guidelines and the CPIC guidelines are sematnically equivalent]]
When changing the semantic structure of the guidelines, as 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 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 the CPIC guidelines:[[File:Protege compare guideline structure.png|frameless|By running the reasoner in the Desktop Protégé, we can ensure that the OUS guidelines and the CPIC guidelines are sematnically equivalent]]
