1. Automatic Generation of Drug Metabolic Pathways from ADME Ontology on OWL-DL Konagaya Akihiko RIKEN Genomic Sciences Center Project Director Advanced Genome Information Technology Research Group

2. Motivation Coming of Personalized Genome Era Polymorphism in Drug Response Genes Detection of Drug-Drug Interaction In silico prediction of individual differences in drug response and drug-drug interactions on multiple dose

3. Issues Detection of Personal Genome Variation Inference of Drug-Drug Interactions on Multiple Dose Quantitative Analysis by Drug Metabolic Pathway Simulation

4. What is a pathway?

5. Pathway KEGG

6. Metabolic Pathway http://www.expasy.org/cgi-bin/show_thumbnails.pl

7. Typical Pathway Analogy

8. Primitives Body/Cell Approaches for Metabolic Pathway Models Static Approach Dynamic Approach Generated from primitive reactions depending on “Trigger” Trigger KEGG http://www.genome.jp/kegg/ A Priori Defined

9. Why Dynamic Approach? Combinatorial Explosion of Molecular Pathways Integration of Continuants and Processes on Primitive Molecular Interactions Representation of Pathways as Aggregation of Primitive Molecular Events

10. How many colors can you see in rainbow?

11. Real Rainbow Color All the colors you can see with your own eyes! From 360 nm ～ 400 nm to 760 nm ～ 830 nm

12. Explicit Knowledge of Colors Red Yellow Green Blue Indigo Purple Orange

13. Ontology for Rainbow Colors #800080 RGB Value #000080 #0000FF #008000 #FFFF00 #FF8000 #FF0000 Red Yellow Green Blue Indigo Purple Orange

14. Which are Purple? #800070 #800060 #500080 #800050#700080 #600080 #800080

15. Color Representation by Primitives R: 700nm, G: 546.1nm, B: 435.8nm. RGB Representation ? Purple Red 360nm830nm ???

16. Ontology Schema

17. 基本要素インスタンスによる 静的クラス（ continuants) と動的クラス (process) の統合 「プロセス」を定義するために必要十分な「物」の関係 Trigger (SN-38@lever) Situated (Carboxyl esterase@lever) Resultant (SN-38@lever) Process (Irinotecan-SN38 Metabolism@lever)

18. 基本要素インスタンスの 重合による現実世界の記述 薬相互作用オントロジーでの例（吉川、有熊、小長谷、２００６）

19. Prototype System

20. Controlled Vocabulary

21. Generated Pathway

22. Detected Drug Interactions

23. Ontology-driven Hypothetical Assertion

24. Conclusion Drug Interaction Ontology can be represented by OWL-DL in terms of processes, continuants and events. Drug metabolic pathways can be dynamically generated by the aggregation of primitive molecular events with OWL-DL and Prolog. Drug interaction can be detected by logical inference and mapped onto drug interaction ontology.

25. Future Works Expansion of Drug Interaction Ontology Automatic Generation of ADME models Integration of Drug Interaction Ontology and ADME simulation

26. Acknowledgement Sumi Yoshikawa RIKEN GSC Ryuzo Azuma RIKEN GSC Takeo Arikuma Tokyo Institute of Technology Kentaro Watanabe Tokyo Institute of Technology (Hitachi Ltd., Japan. ) Kazumi Matsumura RIKEN GSC (DAIICHI PURE CHEMICALS CO., LTD., Japan. )

27. ご静聴ありがとうございました。 Thank You for Listening