Werner CEUSTERS, MD Center of Excellence in Bioinformatics and Life Sciences, and

1. CHSS Data Center Work WeekendOntology, Terminology, and Cardiovascular SurgeryNov 21, 2008 – Toronto, Canada Werner CEUSTERS, MD Center of Excellence in Bioinformatics and Life Sciences, and National Center for Biomedical Ontology, University at Buffalo, NY, USA

2. 1959 - 2008 Short personal history 1977 2006 2004 1989 1992 2002 1995 1998 1993

3. Structure of this presentation • Data and where they (should) come from • Realism-based ontology • Referent Tracking • How to build ontologies from terminologies • How to link to patient data • How can disparate views been accommodated

4. The central hypothesis • For disease registries to facilitate meaningful multi-institutional outcomes analysis, there must be: • Common language = nomenclature, • Mechanism of data collection (database or registry) with an established uniform core data set, • Mechanism of evaluating case complexity, • Mechanism to ensure and verify data completeness and accuracy, • Collaboration between medical subspecialties. JP Jacobs et.al. Nomenclature and Databases — The Past, the Present, and the Future: A Primer for the Congenital Heart Surgeon. Pediatr Cardiol (2007)

5. Would this do ? • For disease registries to facilitate meaningful multi-institutional outcomes analysis, there must be: • Whatever sort of Common language = nomenclature, • Whatever sort of Mechanism of data collection (database or registry) with an established uniform core data set, • Whatever sort of Mechanism of evaluating case complexity, • Whatever sort of Mechanism to ensure and verify data completeness and accuracy, • Whatever sort of Collaboration between medical subspecialties. ?

6. The answer is clearly … • … No ! • There are • many such animals • of various sorts, • which all have shortcomings, • and therefore lead to the creation of even more such animals, • which finally end up suffering – more or less - from the same flaws.

7. Alagille Syndrome Aortic Coarctation Arrhythmogenic RV Dysplasia Cor Triatriatum ... Alagille Syndrome Aortic Coarctation Arrhythmogenic RV Dysplasia Cor Triatriatum ... ? Aortic Coarctation Arrhythmogenic RV Dysplasia Cor Triatriatum ... Mesh 2008: congenital heart defects All MeSH Categories Diseases Category Cardiovascular Diseases Cardiovascular Abnormalities Heart Defects, Congenital All MeSH Categories Diseases Category Congenital, Hereditary, and Neonatal Diseases and Abnormalities Congenital Abnormalities Cardiovascular Abnormalities Heart Defects, Congenital All MeSH Categories Diseases Category Cardiovascular Diseases Heart Diseases Heart Defects, Congenital

8. SNOMED-CT version 2008.01.7AC

9. SNOMED-CT’s‘Fallot’s trilogy’ versus ‘Fallot’s triad’

10. Trilogy of Fallot • Definition: • Combination of pulmonary valve stenosis and atrial septal defect with right ventricular hypertrophy. • Typical representational mistake: • From (correctly, if the definition is right) : • ‘a patient which has Fallot’s triad • has a pulmonary valve stenosis, • has an atrial septal defect, • has a right ventricular hypertrophy.’ • To (wrong, even if the definition is right) : • ‘a Fallot’s triad • is a pulmonary valve stenosis, • is an atrial septal defect, • is a right ventricular hypertrophy.’

11. In general: some alarming publications • Why most published research findings are false. Ioannidis JPA (2005). PLoS Med 2(8): e124. • Institute for Clinical Research and Health Policy Studies, Department of Medicine, Tufts-New England Medical Center, Tufts University School of Medicine, Boston, Massachusetts. • Why Current Publication Practices May Distort Science. Young NS, Ioannidis JPA, Al-Ubaydli O (2008, October 7) PLoS Med 5(10): e201. doi:10.1371/journal.pmed.0050201. • Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland,

12. Key question: Why is this ?

13. ‘The spectrum of the Health Sciences’ Turning data in knowledge http://www.uvm.edu/~ccts

14. ? What is missing here ? Turning data in knowledge http://www.uvm.edu/~ccts

15. Source of all data Reality !

16. data organization model development further R&D (instrument and study optimization) add verify use Δ= outcome Generic beliefs application Today’s data generation and use observation & measurement

17. representation reality Key components data information generates generates generates influences • Players • HIT • Outcomes knowledge hypotheses about

18. Current deficiencies • At the level of reality: • Desired outcomes different for distinct players • Competing interests • Multitude of HIT applications and paradigms • At the level of representations: • Variety of formats • Silo formation • Doubtful semantics • In their interplay: • Very poor provenance or history keeping • No formal link with that what the data are about • Low quality

19. Where should we go?

20. A digital copy of the world Ultimate goal (at least mine)

21. Requirements for this digital copy • R1: A faithful representation of reality • R2 … of everything that is digitally registered, what is generic scientific theories what is specific what individual entities exist and how they relate • R3: … throughout reality’s entire history, • R4 … which is computable in order to … … allow queries over the world’s past and present, … make predictions, … fill in gaps, … identify mistakes, ...

22. In fact … the ultimate crystal ball

23. The ‘binding’ wall How to do it right ? A cartoon of the world

24. Realism-based Ontology Major problems Solutions • A mismatch between what is - and has been - the case in reality, and representations thereof in: • (generic) Knowledge repositories, and • (specific) Data and Information repositories. • An inadequate integration of a) and b). P h i l o s o p h y H I T Philosophical realism Referent Tracking

25. Realism-based Ontology

26. ‘Ontology’: one word, two meanings • In philosophy: • Ontology(no plural) is the study of what entities exist and how they relate to each other; • In computer science and (biomedical informatics) applications: • An ontology(plural: ontologies) is a shared and agreed upon conceptualization of a domain; • Our ‘realist’ view within the Ontology Research Group combines the two: • We use realism, a specific theory of ontology, as the basis for building high quality ontologies, using reality as benchmark.

27. Realism-based ontology • Basic assumptions: • reality exists objectively in itself, i.e. independent of the perceptions or beliefs of cognitive beings; • reality, including its structure, is accessible to us, and can be discovered through (scientific) research; • the quality of an ontology is at least determined by the accuracy with which its structure mimics the pre-existing structure of reality.

28. concept Embedded in Terminology Semantic Triangle object term However: the dominant view in Comp Sc is conceptualism

29. class isa P P P P P P P P P P P P The concept-based view

30. extension-of universal instance-of class member-of P P P P P P P P Defined class P P P P The realism-based view e.g. human e.g. all humans e.g. all humans in this room

31. Ontology Terminology

32. The ‘terminology / ontology divide’ • Terminology: • solves certain issues related to language use, i.e. with respect to how we talk about entities in reality (if any); • Relations between terms / concepts • does not provide an adequate means to represent independent of use what we talk about, i.e. how reality is structured; • Women, Fire and Dangerous Things (Lakoff). • Ontology (of the right sort): • Language and perception neutral view on reality. • Relations between entities in first-order reality

33. Terminological versus Ontological approach • The terminologist defines: • ‘a clinical drug is a pharmaceutical product given to (or taken by) a patient with a therapeutic or diagnostic intent’. (RxNorm) • The ontologist thinks: • Does ‘given’ includes ‘prescribed’? • Is manufactured with the intent to … not sufficient? • Are newly marketed products – available in the pharmacy, but not yet prescribed – not clinical drugs? • Are products stolen from a pharmacy not clinical drugs? • What about such products taken by persons that are not patients? • e.g. children mistaking tablets for candies.

34. Cardiovascular surgery examples • Systemic venous anomaly, SVC, Bilateral SVC • Systemic venous anomaly, SVC, Bilateral SVC, Innominate absent • Systemic venous anomaly, SVC, Bilateral SVC, Innominate present • VA valve overriding • VA valve overriding, Aortic valve • VA valve overriding, Left sided VA Valve • VA valve overriding, Pulmonary valve • VA valve overriding, Right sided VA Valve • VA valve overriding-modifier for degree of override, Override of VA valve ,50% • VA valve overriding-modifier for degree of override, Override of VA valve .90% • VA valve overriding-modifier for degree of override, Override of VA valve 50–90% JP. Jacobs et.al. The nomenclature, definition and classification of cardiac structures in the setting of heterotaxy. Cardiol Young 2007; 17(Suppl. 2): 1–28

35. Representation and Reference terms concepts about First Order Reality The semantic triangle revisited concepts objects terms

36. representational units universals particulars Terminology Realist Ontology Representation and Reference terms concepts about objects First Order Reality

37. Terminology Realist Ontology Representation and Reference terms concepts representational units about objects universals particulars First Order Reality

38. Terminology Realist Ontology Representation and Reference representational units terms concepts cognitive units communicative units about objects universals particulars First Order Reality

39. Representational units in various • forms about (1), (2) or (3) (2) Cognitive entities which are our beliefs about (1) (1) Entities with objective existence which are not about anything Three levels of reality in Realist Ontology Terminology Realist Ontology Representation and Reference representational units cognitive units communicative units universals particulars First Order Reality

40. ‘atrial septal defect’ ‘W. Ceusters’ ‘my heart defect’ DIAGNOSIS my doctor’s work plan my doctor’s diagnosis INDICATION my doctor’s computer my doctor PATHOLOGICAL STRUCTURE PERSON me my ASD DISEASE DRUG my blood pressure BLOOD PRESSURE MOLECULE The three levels in medical practice Generic Specific 3. Representation 2. Beliefs (knowledge) 1. First-order reality

41. Terminology is too reductionist What concepts do we need? How do we nameconcepts properly?

42. The power of realism in ontology design Reality as benchmark ! 1. Is the scientific ‘state of the art’ consistent with biomedical reality ?

43. The power of realism in ontology design Reality as benchmark ! 2. Is my doctor’s knowledge up to date?

44. The power of realism in ontology design Reality as benchmark ! 3. Does my doctor have an accurate assessment of my health status?

45. The power of realism in ontology design Reality as benchmark ! 4. Is our terminology rich enough to communicate about all three levels?

46. The power of realism in ontology design Reality as benchmark ! 5. How can we use case studies better to advance the state of the art?

47. Referent Tracking

48. The same type of location code used in relation to three different events might or might not refer to the same location. PtID Date ObsCode Narrative Three references of hypertension for the same patient denote three times the same disease. 5572 5572 47804 5572 5572 5572 298 298 5572 2309 5572 12/07/1990 22/08/1993 12/07/1990 01/04/1997 03/04/1993 01/04/1997 22/08/1993 17/05/1993 04/07/1990 21/03/1992 04/07/1990 58298795 9001224 26442006 81134009 9001224 26442006 79001 26442006 9001224 2909872 79001 Other lesion on other specified region Essential hypertension Closed fracture of radial head Accident in public building (supermarket) Accident in public building (supermarket) closed fracture of shaft of femur Accident in public building (supermarket) Essential hypertension Fracture, closed, spiral closed fracture of shaft of femur closed fracture of shaft of femur 5572 04/07/1990 79001 Essential hypertension 0939 24/12/1991 255174002 benign polyp of biliary tract If the same fracture code is used for the same patient on different dates, then these codes might or might not refer to the same fracture. 2309 21/03/1992 26442006 closed fracture of shaft of femur If two different fracture codes are used in relation to observations made on the same day for the same patient, they might refer to the same fracture If two different tumor codes are used in relation to observations made on different dates for the same patient, they may still refer to the same tumor. The same fracture code used in relation to two different patients can not refer to the same fracure. 0939 20/12/1998 255087006 malignant polyp of biliary tract Another problem to solve: how many disorders?

49. Requirements for a digital copy of the world • R1: A faithful representation of reality • R2 … of everything that is digitally registered, what is generic scientific theories  realism-based ontologies what is specific what individual entities exist and how they relate • R3: … throughout reality’s entire history, • R4 … which is computable in order to … … allow queries over the world’s past and present, … make predictions, … fill in gaps, … identify mistakes, ...

50. The reality: a digital copy of part of the world Applying the grid should not give a distorted representation of reality, but only an incomplete representation !!!