1. © University of Manchester Intermediate Representations Taming the complexity monster(s) Dr Jeremy Rogers Manchester University Jeremy.e.rogers@manchester.ac.uk BioHealth Informatics Group

2. © University of Manchester Ontology Engineering Complexity Monsters ►Computation ►The Domain ►Artefacts ►Understanding

3. © University of Manchester Domain Complexity Medicine is big ►Very large and inherently complex ►975,354 distinct UMLS concepts ►but this is still too small

4. © University of Manchester Domain Complexity Medicine is big UMLS: 975,000 different medical concepts 1980199019911992199319941995199619971998 19992000200120022003 Concepts 150,000 100,000 50,000 200,000 250,000 300,000 Pathology II (1980) (V 3.0) (V 3.1) (V 3.2) (V 3.3) (V 3.4) (V 3.5) SNOMED II (1979) SNOMED International SNOMED RT (Beta) (V 3.0) (V 3.1) (V 3.2) (V 3.3) (V 3.4) (V 3.5) SNOMED CT 344,000 (Jan 2003)

5. © University of Manchester Domain Complexity Medicine is changing New entities defined… Charcot-Marie-Tooth 1:2500 genetically determined peripheral neuropathy 1975 (ICD) - one code 1996 (Steadmans) – 3 codes 2003 (OMIM) – 46 phenotypic variants, 39 identified locus …old ones consigned to history

6. © University of Manchester Domain Complexity But this is tip of iceberg… ►15496 OMIM UIDs (1 Feb 2006) ►Conditions probably or definitely at least partly genetically determined, including: ►107700 Appendicitis ►600631 Bed Wetting ►604324 Adult Acne ►177900 Psoriasis ►103780 Alcoholism ►188890 Tobacco Addiction ►606349 Pathologic Gambling ►119915 Cluster Headache ►607504 Benign Sexual Headache ►220700 Deafness ►125480 Depression/Mania ►109200 Male pattern baldness ►179600 Raynaud Disease 10000 - 5000 - 15000 - 196519701975198019851990199520002005 10,000 14,737 15,496

7. © University of Manchester Domain Complexity Multiple User Views ►Different Purpose ►[Physician] – where is the pain (and the lesion)? ►[Pharmacologist] – what is physiology of pain receptors and conduction? ►[Neurologist] – in phantom limb pain, how is pain perceived? ►Different focus ►Ontology for diabetic Sx: ►Abscess:Locus(finger, hand, forearm, arm, shoulder, neck, face, scalp, chest, abdomen, back, thigh, calf, shin, forefoot or toe) ►Ontology for diabetic Rx: ►Penicillin – IndicatedFor – Abscess:Locus(Skin) ►Ischaemia:Locus(finger, hand, forearm, arm, shoulder, neck, face, scalp, chest, abdomen, back, thigh, calf, shin, forefoot or toe)

8. © University of Manchester Domain Complexity Needs of external KBs ►Need for lots of rules ►Form on [Hand] should have options [left, right] ►Form on [Palm of hand] should have options [left, right] ►Form on [Finger] should have options [left, right] ►Form on [Thumb] should have options [left, right] ►Form on [First metacarpal] should have options [left, right] ►Etc. etc. ►Obscure categories required for parsimony ►ALL Forms on [mirror-imaged body structures] OR [their subparts] should have option ANY [laterality] ►ALL Forms on [respiratory disease] should have options [cough, wheeze] ►ALL Forms on [symptoms] should have option ANY [severity]

9. © University of Manchester Domain Complexity Polyhierarchies ►Requirement for multiaxial classification ►World is used to monoaxial classification ►Very large domain  very large polyhierarchies ►Impossible to accurately construct by hand ►Inherently confusing to navigate ►The smallprint, if made explicit, overwhelms us

10. © University of Manchester Artefactual Complexity Unreadable notations (ClinicalSituation which )) isCharacterisedBy (presence which isExistenceOf (UrgeToVoidUrineOrFaeces which hasProcessActivity (ProcessActivity which hasQuantity (Level which hasMagnitude highLevel)))) isCharacterisedBy (presence which isExistenceOf AbdominalStraining) >) (XrayComputedTomography which hasPart (Injecting which actsOn RadioopaqueContrastMedium)) name ContrastCTScan

11. © University of Manchester Artefactual Complexity Workarounds ►Limitations in formalism  Workarounds

12. © University of Manchester Cognitive Complexity ►Scale of task ►Multiple authors ►Quality control and assurance ►Formal ontologies require great precision ►Poor debugging tools ►Natural Language can misdirect

13. © University of Manchester Complexity Effect on the user Syntactic confusion – I can’t read this Navigational Confusion – I don’t need most of this Navigational Uncertainty – where am I ? Editorial Uncertainty – atom or primitive ? Editorial Confusion – what recipe ?

14. © University of Manchester #1 Challenge for Ontology Engineering: Hide the complexity

15. © University of Manchester Intermediate Representations From this to this… (SurgicalDeed which isCharacterisedBy (performance whichG isEnactmentOf (Dividing whichG < playsClinicalRole SurgicalRole actsSpecificallyOn HeartValve hasSubprocess (TemporalFeature which < isSpecificImmediateConsequenceOf VolitionalAct involves Heart hasSpecificConsequence (BodyProcess which < isSpecificFunctionOf Heart hasProcessActivity (ProcessActivity which hasQuantity (Level which hasMagnitude undetectedLevel)) >) hasPathologicalStatus pathological >)>))) MAIN replacing ACTS_ON heart valve HAS_ FEATURE induced arrest of heart (And back again)

16. © University of Manchester Demonstration CLAW

17. © University of Manchester HOW?

18. © University of Manchester Intermediate Representation Semantic Expansion MAIN excision action HAS_APPROACH transethmoidal SITE pituitary structure transethmoidal leg excision - action pituitary structure open partial etc. ‘DESCRIPTORS’ (Route which passesThrough EthmoidSinus) LowerExtremity Excising PituitaryGland surgicallyOpen partial GALEN Common Reference Model HAS_APPROACH ACTS_ON SITE HAS_EXTENT HAS_LOCATION IS_PART_OF etc. ‘LINKS’... hasSubprocess (Approaching hasMeans......hasSubprocess (Approaching hasMeans (Route passesThrough......hasSubprocess (Approaching hasMeans (TranstubalRoute hasDirection... GALEN Common Reference Model

19. © University of Manchester Intermediate Representation Context sensitive substitution (SurgicalDeed which isMainlyCharacterisedBy (performance whichG isEnactmentOf ((Excising which playsClinicalRole SurgicalRole) whichG < hasSpecificSubprocess (SurgicalApproaching whichG hasPhysicalMeans ((Route which passesThrough EthmoidBone))) actsSpecificallyOn PituitaryGland>))) hasProjection (('READ' schemeVersion 'default') code '71000' 'code'); extrinsically hasDissectionRubric 'READ 71000 Transethmoidal hypophysectomy'. RUBRIC ‘Transethmoidal hypophysectomy’ SOURCE ‘READ’ CODE ‘71000’ MAIN excision action HAS_APPROACH transethmoidal SITE pituitary structure Descriptor Mappings Link Mappings

20. © University of Manchester Intermediate Representation Supporting Infrastructure Dissection Library Expanded Dissections Mapping Descriptors Links Expansion Algorithm Existing Classification Dissections New Descriptors New Links ClaW: Check & Iterate Derived Classification GRAIL Expansion compare So where did the complexity go?

21. © University of Manchester Demonstration TIGGER

22. © University of Manchester Demonstration DOPAMINE

23. © University of Manchester Drug Ontology & Dopamine

24. © University of Manchester Demonstration CLINERGY 2

25. © University of Manchester Ontologies in Action IndicationCodeRubric Atrial fibrillation14AN.H/O atrial fibrillation 3272.ECG: atrial fibrillation 3273.ECG: atrial flutter 7936AIV pacer control of A Fib G573.Atrial fibrillation / flutter Patient ID: 4578 Medication: DITA906 DISR10514B Problem List: 183... (Oedema) 1B17.. (Depressed) G5732. (Paroxysmal Atrial fibrillation) G73z0. (Intermittent claudication) H3.... (Chronic obstructive pulm.dis.) 137S.. (Ex smoker) 246... (O/E - blood pressure reading) 442... (Thyroid hormone tests) 44P... (Serum cholesterol) 7L172. (Blood withdrawal for testing) Ontology IDProductRubric 345031(oral dig)DITA905Digoxin 125 mcg tab 345031DITA906Digoxin 250 mcg tab 345031DITA908Digoxin 62.5 mcg tab IDENT “9099269” MAIN digoxin PROPERTIES HAS_DRUG_FEATURE physiological action WHICH_IS process ACTS_ON heart HAS_DRUG_FEATURE indication FOR treating ACTS_ON supraventricular arrhythmia HAS_DRUG_FEATURE indication FOR treating ACTS_ON atrial fibrillation HAS_DRUG_FEATURE information source IS_PART_OF interaction appendix 345031 Oral Digoxin tablet 305075 Digoxin injection 305084 Digoxin Liquid 329308 Digoxin elixir 305093 Digoxin Paed inj 9099269 Systemic Digoxin G57.. Cardiac dysrhythmias G573. Atrial fibrillation and flutter G5730 Atrial fibrillation G5731 Atrial flutter G5732 Paroxysmal atrial fibrillation G573z Atrial fibrillation and flutter NOS