1. Social Pharmacy and Pharmacoepidemiology Lister Hill National Center for Biomedical Communications Text-based Discovery in Biomedicine The Architecture of the DAD-system Marc Weeber 1,2, Henny Klein 1, Alan R. Aronson 2, Jim G. Mork 2, Lolkje T. W. de Jong - van den Berg 1, Rein Vos 1,3 1 Department of Social Pharmacy and Pharmacoepidemiology, Groningen University Institute for Drug Exploration, The Netherlands 2 Lister Hill National Center for Biomedical Communication, National Library of Medicine, Bethesda, MD 3 Health Ethics and Philosophy, Faculty of Health Sciences, University of Maastricht, The Netherlands

2. Social Pharmacy and Pharmacoepidemiology Lister Hill National Center for Biomedical Communications Introduction Goal: Finding new biomedical knowledge through the combination of existing knowledge as represented in the medical literature Motivation: Prevention of re-inventing the wheel, re-usage of specific knowledge outside the original domain of discovery

3. Social Pharmacy and Pharmacoepidemiology Lister Hill National Center for Biomedical Communications Swanson AB: Raynaud’s disease is characterized by high blood viscosity and high platelet aggregation BC: Fish oil is known to reduce blood viscosity and platelet aggregation ACB ?

4. Social Pharmacy and Pharmacoepidemiology Lister Hill National Center for Biomedical Communications Vos and Rikken Drugs instead of diet factors Intermediate (B) terms are adverse drug reactions Drug – Adverse drug reactions – Disease: The DAD-system Vos (1991) Drugs looking for diseases

5. Social Pharmacy and Pharmacoepidemiology Lister Hill National Center for Biomedical Communications Existing Techniques Swanson & Smalheiser: Single words/multi word terms MEDLINE titles No statistics Gordon & Lindsay: Single words/multi word terms Information Retrieval statistics Replication of Swanson’s discoveries

6. Social Pharmacy and Pharmacoepidemiology Lister Hill National Center for Biomedical Communications New Techniques Use of UMLS concepts PubMed MetaMap: mapping free text (MEDLINE titles and abstracts) to concepts Interactive web interface

7. Social Pharmacy and Pharmacoepidemiology Lister Hill National Center for Biomedical Communications Two-step Approach Open discovery, generating a hypothesis A?? Closed discovery, testing a hypothesis AC?

8. Social Pharmacy and Pharmacoepidemiology Lister Hill National Center for Biomedical Communications Why UMLS Concepts? Use of only biomedically relevant information Useful transition from single word to multi word term Semantic information (semantic types) for filtering (e.g. select only Disease or Syndrome)

9. Social Pharmacy and Pharmacoepidemiology Lister Hill National Center for Biomedical Communications DAD-system Meta- thesaurus Specialist Lexicon PubMedSemantic Network MetaMap KS

10. Social Pharmacy and Pharmacoepidemiology Lister Hill National Center for Biomedical Communications DAD-system Meta- thesaurus MySQL Database Specialist Lexicon PubMedSemantic Network MetaMap Filter Txt2Con QueryShow Select KS

11. Social Pharmacy and Pharmacoepidemiology Lister Hill National Center for Biomedical Communications DAD-system Meta- thesaurus MySQL Database Specialist Lexicon PubMedSemantic Network MetaMap Filter Txt2Con QueryShow Select KS

12. Social Pharmacy and Pharmacoepidemiology Lister Hill National Center for Biomedical Communications A Open Discovery Query (user input): raynaud’s disease

13. Social Pharmacy and Pharmacoepidemiology Lister Hill National Center for Biomedical Communications A Open Discovery Mapping text to concept through MetaMap: Raynaud's Disease [Disease or Syndrome]

14. Social Pharmacy and Pharmacoepidemiology Lister Hill National Center for Biomedical Communications A Open Discovery Synonym lookup: Raynaud's syndrome Raynaud's disease /phenomenon Variant generation: e.g. syndrome / syndromes

15. Social Pharmacy and Pharmacoepidemiology Lister Hill National Center for Biomedical Communications A Open Discovery PubMed query: raynaud OR raynauds Processing: query in titles and abstracts Result: 1,246 MEDLINE citations

16. Social Pharmacy and Pharmacoepidemiology Lister Hill National Center for Biomedical Communications A Open Discovery Text to concept mapping of all citations Sentences with Raynaud’s disease Result: 1,278 UMLS concepts

17. Social Pharmacy and Pharmacoepidemiology Lister Hill National Center for Biomedical Communications A Open Discovery Select functional/physiological concepts Semantic types in filter: Body Location or Region Biologic Function Cell Function Phenomenon or Process Physiologic Function Tissue

18. Social Pharmacy and Pharmacoepidemiology Lister Hill National Center for Biomedical Communications AB Open Discovery Result: 57 Concepts Frequency range: 1- 18

19. Social Pharmacy and Pharmacoepidemiology Lister Hill National Center for Biomedical Communications AB Open Discovery Selected B-concepts: Plasma Viscosity Level Blood Viscosity Platelet Adhesiveness Platelet Aggregation Effects, Blood Coagulation

20. Social Pharmacy and Pharmacoepidemiology Lister Hill National Center for Biomedical Communications AB Open Discovery Variants: plasma, plasmas viscosity, viscous, aggregation, aggregations, aggregating coagulation, coagulating

21. Social Pharmacy and Pharmacoepidemiology Lister Hill National Center for Biomedical Communications AB Open Discovery PubMed query: blood coagulation OR blood viscosity OR plasma viscosity OR platelet adhesiveness OR platelet aggregation Result: 10,611 MEDLINE citations

22. Social Pharmacy and Pharmacoepidemiology Lister Hill National Center for Biomedical Communications AB Open Discovery Concepts in sentences with B-concepts: 7,702 Concepts not in Raynaud sentences: 6,747

23. Social Pharmacy and Pharmacoepidemiology Lister Hill National Center for Biomedical Communications AB Open Discovery Filter for dietary related concepts Semantic types in filter: Vitamin Lipid Element, Ion, or Isotope

24. Social Pharmacy and Pharmacoepidemiology Lister Hill National Center for Biomedical Communications ABC Open Discovery Eicosapentaenoic Acid Fish Oil Fatty Acids, Omega 3 MAXEPA Omega-3 Polyunsaturated Fatty Acid Cod Liver Oil Salmon Oil Result: 206 Concepts Rank order on relations Fish oil related concepts:

25. Social Pharmacy and Pharmacoepidemiology Lister Hill National Center for Biomedical Communications AC Closed Discovery Eicosapentaenoic Acid Fish Oil Fatty Acids, Omega 3 MAXEPA Omega-3 Polyunsaturated Fatty Acid Cod Liver Oil Salmon Oil Raynaud’s Disease

26. Social Pharmacy and Pharmacoepidemiology Lister Hill National Center for Biomedical Communications AC Closed Discovery 1,246 citations 1,278 concepts 479 common concepts 463 citations 1,795 concepts

27. Social Pharmacy and Pharmacoepidemiology Lister Hill National Center for Biomedical Communications AC Closed Discovery Functional / Physiological Filter 45 B-concepts

28. Social Pharmacy and Pharmacoepidemiology Lister Hill National Center for Biomedical Communications AC Closed Discovery B Known concepts: Plasma viscosity level Blood Viscosity Platelet Adhesiveness Platelet Aggregation Effects, Blood Coagulation New concepts: Vasodilatation Veins, Capillaries Dinoprostone Fibrinolysis Deformability Rheology

29. Social Pharmacy and Pharmacoepidemiology Lister Hill National Center for Biomedical Communications Juxtaposition

30. Social Pharmacy and Pharmacoepidemiology Lister Hill National Center for Biomedical Communications Success / Failure +Simulation of Raynaud’s disease – fish oil and migraine – magnesium +Discovery of new therapeutic applications for thalidomide -Mapping (Mg = milligram / magnesium) -Association defined by co-occurrence

31. Social Pharmacy and Pharmacoepidemiology Lister Hill National Center for Biomedical Communications Future Better semantic analysis: increase(A,B) and decrease(B,C) Better user interface More databases e.g. finding genetic bases for diseases