Diese Präsentation wurde erfolgreich gemeldet.

Samwald cshals2013

2

Teilen

1 von 26
1 von 26

Weitere Verwandte Inhalte

Samwald cshals2013

  1. 1. Semantically Enabling Genetic Medicine Facilitating Patient - Guideline Matching and Pharmacogenetic Clinical Decision Support Matthias Samwald Medical University of Vienna & Vienna University of Technology W3C Semantic Web for Healthcare and Life Science Interest Group
  2. 2. Drug efficacy and toxicity can vary drastically between patients with different genetic profiles
  3. 3. The drug warfarin is a popular example of clinical pharmacogenomics
  4. 4. Such pharmacogenomic information is becoming available for many other drugs
  5. 5. OWL 2 for pharmacogenomic knowledge representation and clinical decision support
  6. 6. Allele definitions in the Human Cytochrome P450 Allele Nomenclature Database
  7. 7. Allele definitions in PharmGKB
  8. 8. 1 Class: 'human with CYP2C9 *3' 2 EquivalentTo: 3 has some rs1057910_C 4 SubClassOf: 5 has some 'CYP2C9 *3', 6 (has some rs1057910_C) and 7 (has some rs1057911_A) and 8 (has some rs1799853_C) and 9 (has some rs2256871_A) and 10 (has some rs28371685_C) and 11 (has some rs72558188_AGAAATGGAA) and 12 (has some rs72558189_G) and 13 (has some rs9332239_C) ... Allele definitions in OWL 2
  9. 9. 1 Class: 'human with CYP2C9 *18' 2 EquivalentTo: 3 (has some rs1057910_C) and 4 (has some rs1057911_T) and 5 (has some rs72558193_C) 6 SubClassOf: 7 has some 'CYP2C9 *18', 8 (has some rs1057910_C) and 9 (has some rs1057911_T) and 10 (has some rs1799853_C) and 11 (has some rs2256871_A) and 12 (has some rs28371685_C) and 13 (has some rs28371686_C) and 14 (has some rs56165452_T) and 15 (has some rs57505750_C) and 16 (has some rs67807361_C) and ... Allele definitions in OWL 2
  10. 10. Dosing guideline from an FDA drug label
  11. 11. Dosing guideline from an FDA drug label 1 Class: 'human triggering CDS rule 9' 2 Annotations: 3 CDS_message "0.5-2 mg warfarin per day should be considered 4 as a starting dose range for a patient with this genotype 5 According to the warfarin drug label." 6 EquivalentTo: 7 (has some 'CYP2C9 *1') and 8 (has some 'CYP2C9 *3') and 9 (has exactly 2 rs9923231_T) (of course, entities in the ontology are mapped to other Semantic Web resources such as Bio2RDF)
  12. 12. Definitions can become quite complex – OWL reasoning helps identify inconsistencies and lacking definitions
  13. 13. Describing an individual patient in OWL 1 Individual: example_patient 2 Types: 3 human, 4 (has some rs1208_A) and (has some rs1208_G), 5 (has some rs8192709_C) and (has some rs8192709_T), 6 (has some rs9934438_A) and (has some rs9934438_G), 7 has exactly 2 rs10264272_C, 8 has exactly 2 rs9923231_T, 9 has exactly 2 rs12720461_C, 10 (has some ‘CYP2C9 *1’) and (has some ‘CYP2C9 *3’), 11 has exactly 2 ‘CYP2C19 *1’, 12 (has exactly 3 CYP2D6) and (has exactly 2 ‘CYP2D6 *1’) 13 and (has exactly 1 ‘CYP2D6 *2’) ... heterozygous SNP variants homozygous SNP variants allelic variants and CNV
  14. 14. Describing an individual patient in OWL 1 Individual: example_patient 2 Types: 3 human, 4 (has some rs1208_A) and (has some rs1208_G), 5 (has some rs8192709_C) and (has some rs8192709_T), 6 (has some rs9934438_A) and (has some rs9934438_G), 7 has exactly 2 rs10264272_C, 8 has exactly 2 rs9923231_T, 9 has exactly 2 rs12720461_C, 10 (has some ‘CYP2C9 *1’) and (has some ‘CYP2C9 *3’), 11 has exactly 2 ‘CYP2C19 *1’, 12 (has exactly 3 CYP2D6) and (has exactly 2 CYP2D6_star_1) 13 and (has exactly 1 CYP2D6_star_2) ... heterozygous SNP variants homozygous SNP variants allelic variants "0.5 - 2 mg warfarin per day should be considered as a starting dose range for a patient with this genotype according to the warfarin drug label." OWL Reasoner
  15. 15. OWL 2 DL reasoning needs to be fast!!
  16. 16. TrOWL is massively more performant than the HermiT reasoner in classifying our demo ontology HermiT TrOWL Genomic CDS light (2150 classes, 9500 axioms) 3 hours 48 minutes 18 seconds Genomic CDS (2300 classes, 11000 axioms) did not terminate within 6 hours 54 seconds Ontologies have ALCQ expressivity. http://www.genomic-cds.org/ http://trowl.eu/ (Pan et al.) http://hermit-reasoner.com/ (Horrocks, Motik et al.)
  17. 17. How can we put this into the hands of doctors and patients? A prototype based on 2D barcodes
  18. 18. Making pharmacogenomics easier to understand for doctors and patients Making core set of pharmacogenomic data available for every patient Making pharmacogenomic decision support available to every doctor Providing pharmaceutical manufacturers with a basic set of markers for patient stratification that can be made cheaply available for large patient populations through prospective genotyping Curated set of 380+ markers, 50+ pharmacogenes and rule system: The Medicine Safety Code prototype
  19. 19. (data on 385 pharmacogenetic markers are encoded in there) A Medicine Safety Code can be represented as a QR code
  20. 20. Modern mobile devices can successfully decode very compact Medicine Safety Codes
  21. 21. The MSC provides a simple, barrier-free system for storing and interpreting personal pharmacogenomic information (of course, the data from an MSC could also be embedded in an EHR where available)
  22. 22. Clinical decision support messages can be viewed quickly Within 15 seconds in best-case scenarios See recent JAMIA paper for more information Upcoming version will be backed by the ontology and reasoning system I showed you before
  23. 23. Conclusions Still at an early stage (Semantic) Web technologies used for entire contiuum from basic knowledge representation up to deployment in clinical routine OWL 2 ontologies and reasoning could help to make pharmacogenomic knowledge more transparent and error-free OWL 2 could be established as a shared standard for representing (pharmaco-)genetic knowledge??
  24. 24. Future work Partnership with clinics, pharmaceutical companies, genetic testing providers, payers Create optimized reasoner for the specific OWL 2 fragment needed for genomics? (ALCQ with arbitrary cardinalities)
  25. 25. Thanks W3C collaborators: Michel Dumontier (Carleton University) Robert R. Freimuth (Mayo Clinic) Richard Boyce (University of Pittsburgh) Robert L. Powers (Predictive Medicine, Inc.) Joanne S. Luciano (Rensselaer Polytechnic Institute) Eric Prud’hommeaux (W3C) M. Scott Marshall (MAASTRO Clinic) Simon Lin (Marhsfield Clinic) and others

×