Matthias, First, great work. I think this embodies an initial approach we've envisioned for using OWL ontologies for clinical pharmacogenomics. It's able to i) define complex genotypes (as a union/conjunction of alleles) ii) it can define copy number variation (zero, one or more copies of a gene/gene variant), or capture uncertainty in the copy number (e.g. at least one). iii) it points to specific snps variants for a given variant
so, here are some comments: 1. can you provide a description of the specific snp-containing entry e.g. rs9332239_C - i'll generate the appropriate descriptions for Bio2RDF version dbsnp that i'm working on. 2. The class 'Human' specifies 2 of all the genes, so this restricts our cases where CNV plays an important role (from 0 copies to dozens). To what extent is the use of the cardinality restriction on this parent class *essential* for generating the inferred classification? Should this instead be done at the patient level? 3. We should be generating linked data -> Warfarin can point to any of : drugbank or SPL (since PharmGKB and PubChem gets their drug information from DrugBank). Since Bio2RDF hosts Drugbank, we could use those URIs. m. On Wed, Nov 21, 2012 at 10:19 AM, Matthias Samwald < matthias.samw...@meduniwien.ac.at> wrote: > ** > Dear all, > > A preview release (version 0.8) of the Genomic CDS ontology is now > available at > *http://www.genomic-cds.org/ont/genomic-cds.owl* > > There is also a demo version that contains some example patient data: > http://www.genomic-cds.org/ont/genomic-cds-demo.owl > > Among other things, it contains logical representations of pharmacogenetic > alleles and their defining SNPs, as well as logical representations > of selected pharmacogenetic guidelines from the Clinical Pharmacogenetics > Implementation Consortium and the Dutch Pharmacogenetics Working Group. The > Genomic CDS ontology aims to unify several functionalities in a single > resource, being: > * A knowledge base for clinical pharmacogenomics/pharmacogenetics that can > be used for question-answering (e.g., which SNPs are associated with this > drug?) > * A rule base for clinical decision support (e.g., inferring that a > patient with a specific set of SNPs requires a lowered dose of warfarin and > generating a CDS message that can be viewed by clinicians) > * A tool for checking data consistency (e.g., highlighting which allele > definitions in PharmGKB are overlapping, or which clinical decision support > rules are matching the same group of patients) > > The ontology is OWL 2 DL serialized in Manchester Syntax. Protege > 4<http://protege.stanford.edu/download/registered.html>with the TrOWL > reasoner plugin <http://trowl.eu/?page_id=10>is recommended for working > with the ontology. Please note that it the ontology is quite complex, so > reasoning only works on decent hardware. > > The use of OWL 2 (and Manchester Syntax) makes it possible to capture > complex pharmacogenetic definitions and data in a relatively intuitive, yet > ontology-based and machine-readable format. For example, the OWL > description of a few SNPs of a patient looks like this: > > ----------- > Individual: example_patient > Types: > human, > (has some rs10929302_A) and (has some rs10929302_G), > (has some rs1208_A) and (has some rs1208_G), > (has some rs12571421_A) and (has some rs12571421_G), > (has some rs12769205_A) and (has some rs12769205_G), > has exactly 2 rs10264272_C, > has exactly 2 rs10276036_T, > has exactly 2 rs1041983_C, > has exactly 2 rs1042713_G, > ----------- > > Equally, a logical description of SNPs associated with the CYP2C9*3 allele > look like this... > > ----------- > Class: 'human with CYP2C9 *3' > EquivalentTo: > has some rs1057910_C > > > SubClassOf: > has some 'CYP2C9 *3', > (has some rs1057910_C) > and (has some rs1057911_A) > and (has some rs1799853_C) > and (has some rs2256871_A) > and (has some rs28371685_C) > > and (has some rs28371686_C) > and (has some rs56165452_T) > and (has some rs57505750_C) > and (has some rs67807361_C) > and (has some rs72558184_G) > and (has some rs72558187_T) > > and (has some rs72558188_AGAAATGGAA) > and (has some rs72558189_G) > and (has some rs72558190_C) > and (has some rs72558192_A) > and (has some rs72558193_A) > and (has some rs7900194_G) > > and (has some rs9332130_A) > and (has some rs9332131_A) > and (has some rs9332239_C), > ----------- > > ... and a logical description of the group of humans that might require a > specific initial warfarin dose based on their genetic traits looks like this: > > ----------- > Class: 'human triggering CDS rule 7' > > Annotations: > label "human triggering CDS rule 7", > 'CDS message' "3-4 mg warfarin per day should be considered as a > starting dose range for a patient with this genotype according to the > Warfarin drug label (Bristol-Myers Squibb).", > > 'relevant for' > <http://www.genomic-cds.org/ont/genomic-cds.owl#Warfarin> > > EquivalentTo: > (has some 'CYP2C9 *1') > > and (has some 'CYP2C9 *3') > and (has exactly 2 rs9923231_C) > > SubClassOf: > 'Human triggering CDS rule' > ----------- > > To make long-term development and maintenance easier, the ontology is > generated from intuitive spreadsheets (so that independent domain experts can > easily edit and validate the knowledge) and automated imports from primary > datasets such as dbSNP. > > An issue tracker for ontology development is available at > http://code.google.com/p/genomic-cds/issues/list > > Also, a website for the project is under construction at > http://www.genomic-cds.org/ > > The ontology also has a home on BioPortal at > http://bioportal.bioontology.org/ontologies/3179 > > Needless to say, all of this is just a partial research prototype. Not all > required information is in the ontology, some information might be several > months out of date, and accuracy and quality have not been validated. > We can discuss the ontology in today's teleconference call (the first in > the new Wednesday timeslot, an announcement will be sent out soon). > > Cheers, > Matthias Samwald > http://samwald.info/ > > > > -- Michel Dumontier Associate Professor of Bioinformatics, Carleton University Chair, W3C Semantic Web for Health Care and the Life Sciences Interest Group http://dumontierlab.com
