Scale and Context: Issues in Ontologies to link Health- and Bio-Informatics

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Scale and Context Issues in Ontologies to link
Health- and Bio-Informatics

• Alan Rector, Jeremy Rogers, Angus Roberts, Chris
  Wroe Bio and Health Informatics Forum/Medical
  Informatics GroupDepartment of Computer Science,
  University of Manchester
• rector_at_cs.man.ac.ukwww.cs.man.ac.uk/mig
  img.man.ac.ukwww.clinical-escience.orgwww.open
  galen.org

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Organisation of Talk

• Informal presentation, motivation examples
• Intro to logic based ontologies
• How to use logic based ontologies to represent
  scales and context
• Making context modular normalisation
• Recurrent distinctions
• and tests for those distinctions
• Making logic based ontologies usable
• Views and Intermediate Representations
• Summary

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Example Problems of Context

• Classification by multiple axes
• e.g. Molecular action, physiologic, and
  pathological effects
• Chloride transport Cystic fibrosis
• Biological Scope
• eg. Normal/Abnormal, Human/Mouse
• Conceptual view
• e.g. the Digital Anatomist Foundational Model of
  organs vs Clinical convention Is
  the pericardium a part of the heart?

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Basic Approach

• Separate information into independent modules
• Normalise the ontology
• The truth, the whole truth, and nothing but the
  truth
• Add explicit contextual information
• Dont distort the structure
• Add context to it explicitly

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Why use Logic-based Ontologies?
becauseKnowledge is Fractal!
Requirements are Diverse
Coherence without Uniformity!
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Logic-based Ontologies Conceptual Lego
gene
protein
cell
expression
chronic
acute
bacterial
deletion
polymorphism
ischaemic
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Logic-based Ontologies Conceptual Lego
SNPolymorphism of CFTRGene causing Defect in
MembraneTransport of ChlorideIon causing Increase
in Viscosity of Mucus in CysticFibrosis
Hand which isanatomicallynormal
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Logic based ontologies

• A formalisation of semantic nets, frame systems,
  and object hierarchies via KL-ONE and KRL
• is-kind-of implies (logical
  subsumption)
• Dog is a kind of wolf meansAll dogs are
  wolves
• Modern examples DAMLOIL /OWL?)
• Older variants LOOM, CLASSIC, BACK, GRAIL,
  K-REP,

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Logic Based Ontologies The basics
Validating (constraining cross products)
Primitives
Descriptions
Definitions
Reasoning
Thing
red partOf Heart
red partOf Heart
(feature pathological)
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Bridging Bio and Health Informatics

• Define concepts with pieces from different
  scales and disciplines and then combine them
• Polymorphism which causes defect which causes
  disease
• Use concepts which make context explicit
• Hand which is anatomically normal ? has five
  fingers Normal human prostate ? has three
  lobes
• Use different subproperties for different
  contexts
• Abnormalities of clinical parts of the heart

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Bridging Scales with Ontologies
Species
Genes
Function
Disease
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Use composition to express context

• Normal and abnormal
• Hand ? isSubdivisionOf some UpperExtremity
• Hand AnatomicallyNormal ? hasSubdivision
  exactly-5 fingers
• Homologies and Orthologies
• Thumb of Hand of Human ? hasFeature Opposable
• Thumb of Hand of NonHumanPrimate ? hasFeature
  Opposable

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More detailed example
Body
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Represent context and views by variant properties
is_structurally_part_of
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What we want to avoid combinatorial explosions

• The Exploding Bicycle From phrase book to
  dictionary grammar
• 1980 - ICD-9 (E826) 8
• 1990 - READ-2 (T30..) 81
• 1995 - READ-3 87
• 1996 - ICD-10 (V10-19 Australian) 587
• V31.22 Occupant of three-wheeled motor vehicle
  injured in collision with pedal cycle, person on
  outside of vehicle, nontraffic accident, while
  working for income
• and meanwhile elsewhere in ICD-10
• W65.40 Drowning and submersion while in bath-tub,
  street and highway, while engaged in sports
  activity
• X35.44 Victim of volcanic eruption, street and
  highway, while resting, sleeping, eating or
  engaging in other vital activities

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The Cost 1 Normalising (untangling) Ontologies
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The Cost 1 Normalising (untangling)
OntologiesMaking each meaning explicit and
separate
PhysSubstance Protein ProteinHormone
Insulin Enzyme Steroid
SteroidHormone Hormone ProteinHormone
Insulin SteroidHormone
Catalyst Enzyme
PhysSubstance Protein ProteinHormone
Insulin Enzyme Steroid
SteroidHormone Hormone
ProteinHormone Insulin
SteroidHormone Catalyst Enzyme
build it all by combining simple trees
Hormone Substance playsRole-HormoneRole Pro
teinHormone Protein playsRole-HormoneRoleS
teroidHormone Steroid playsRole-HormoneRole
Catalyst Substance playsRole
CatalystRole Insulin ? playsRole HormoneRole
Enzyme ?? Protein playsRole-CatalystRole
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NormalisationBuilding ontologies from orthogonal
trees

• Each tree is homogeneous and based on subsumption
• One prinicple one of function, structure,
  cause,
• Every primitive has exactly 1 primitive parent
• All multiple classification done by the logic
• All self-standing primitives disjoint

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The Cost 2 Clean Distinctions Tests

• Repeating patterns within levels
• Structures vs Substances
• Flavours of part-whole
• Part-whole vs containment, connection, branching
• Process/Event vs Thing (Endurant vs
  Perdurant)
• Repeating patterns across levels
• Multiples at one level act as substances at the
  next
• Substances span levels structures are specific
  to a level

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Repeating Patterns within each level

• Structures vs Substances (Discrete vs Mass)
• Structures are made of substances
• Organs are made of tissue
• Parts portions
• Structures have parts subdivisions,
• Substances have portions
• Portions can have proportions concentrations

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Tests

• Structures (Discrete)
• Can you count it? Is one part different from
  another? Is it made of something(s)?
• Books, organs, ideas, individual cells,
  organisations,
• Substance (Mass)
• Are all bits the same? Can something be made of
  it? Can you talk about A piece of it? A lump
  of it? A stream of it?
• Water, sodium, tissue, blood,

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Repeating Patterns within each level

• Part-whole vs containment
• Parthood is organisational
• The wall is part of the cell
• The cornea is part of the eye
• Containment is physical
• The inclusion is contained in the cell
• The marrow is contained in the bone
• Often occur together
• Nucleus is a part of and contained in the cell
• The retina is part of and contained in the eye

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Tests

• Parts
• If I take the part away, is the whole incomplete?
• If the part is damaged is the whole damaged?
• If I do something to the part do I do something
  to the whole?
• Containment
• Is the contained thing inside the container?
• Is the relationship spatial/physical? (or
  temporal?)

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Repeating Patterns bridging levels

• Multiples of structures at one level behave as
  substances at the next
• Blood is made of in part a multiple of red
  cellsTissue is made of in part a multiple of
  cellsA rash is a multiple of spotsPolyposis
  is a multiple of polypsA flock is a multiple
  of birds
• Multiples are not Sets
• Not defined by members
• Membership can change (intensional rather than
  extensional)
• Action on the singleton is not action on the
  multipleAction on the whole is (usually) action
  on the singletons
• If I treat a spot, I do not treat the rash
• If I treat the rash, I treat the spots

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Tests

• Multiples
• Name for the singleton grain, cell, bird?
• Singletons are countable?
• Multiple is measurable rather than countable?
• Odd to say part-of This cell is part of the
  Arm?

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But make it simple

• Intermediate representations and views
• OWL Detailed Schema is the Assembler Language
• FaCT/SHIQ/ is the machine code
• Almost no one writes in assembler
• let alone machine code
• Separate terms and concepts
• Language/labels from concepts

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Layered Architecture
Protégé OilEd-II ?
DL
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ExampleAn Intermediate Representation for
Surgery

• "Open fixation of a fracture of the neck of the
  left femur"
• MAIN fixing
• ACTS_ON fracture
• HAS_LOCATION neck of long bone
• IS_PART_OF femur
• HAS_LATERALITY left
• HAS_APPROACH open

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The formal assembler version
(SurgicalProcess which isMainlyCharacterisedBy
(performance which isEnactmentOf
(SurgicalFixing which

• hasSpecificSubprocess (SurgicalAccessing
• hasSurgicalOpenClosedness
  (SurgicalOpenClosedness which
• hasAbsoluteState surgicallyOpen))

actsSpecificallyOn (PathologicalBodyStruc
ture which lt involves Bone
hasUniqueAssociatedProcess
FracturingProcess hasSpecificLocat
ion (Collum which
isSpecificSolidDivisionOf
(Femur which
hasLeftRightSelector
leftSelection))gt))))
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Result

• Training time 3 mo ? 3 days 3 days
• Productivity 25/day ? 100/day
• Central reconciliation 50 ? 10
• Local cycle time 3 months ? lt1 week
• Dependencies High ? Low
• Author satisfaction Low ? High
• Disputes Frequent ? Rare
• Repeatability Low ? High

Even Pre Web!
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Navigation vs Retrieval/ReferenceAccess
terminology Reference terminology

• Access follows model of use
• e.g. MeSH, MEDCin
• Hierarchy is what is needed next to hand
• People find easy Software hard
• Retrieval follows model of meaning
• Logic based ontologies
• Hierarchy means is-kind-of / subsumption
• People may find odd Software is easy
• Need Both - visualisations of both
• The logic based structure isnt enough
• Views and intermediate representations

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Whats in a View/ Intermediate Representation?
Language
linguisticgeneration search
User Oriented Structures
semantictransformations Filters
Explicit Context in Ontology Assembler
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SummaryLet the logic engine do the work

• Logic based ontologies can bridge granularities
  represent context explicitly
• And manage the potential combinatorial explosions
• To do so
• Views and Interface usable, flexible easy to
  learn
• Entry, Navigation, Use are different
• Structure explicit modular Normalised
• Conception clean testable distinctions
• Tools Architecture - layered comprehensive
• The logic is the assembly language

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Some Healthcare Terminologies
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Some Healthcare Terminologies

• ICD 9/10
• Traditional paper thesauri
• -CM versions essential for billing (and AM)
• CPT Clinical Procedure Terminology
• Simple list
• Clinical Terms (Read Codes) V2
• Simple hierarchy
• Still dominant in UK general practice
• SNOMED-CT
• At least logic assisted
• Political questions
• NCI Cancer Ontology
• Logic based in parts work in progress

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Others

• Standards Related
• Loinc laboratory data
• Increasingly structured logic assisted
  aspirations
• HL7 Vocabulary TC
• Specialised vocabularies Inspiration for OHT
• Links to RxNorm
• Snomed Dicom Microglossary (SDM)
• Image related information not related tNOMED
• Open Source
• OpenGALEN Common Reference Model
• Logic based multilingual a resource rather
  than a terminology
• Basis of UK Drug Ontology
• Open Health Terminology
• Watch this space
• Focusing on UMLS
• Likely to be at least logic assisted

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Special Purpose

• Anatomy
• Digital Anatomist Foundational Model of
  AnatomyFMA
• Principled frame based representation
• Superb reference point for structural anatomy
• Needs functional and clinical supplements
• http//sig.biostr.washington.edu/projects/da/
• Drugs
• RxNorm and VA projects
• See Steve Brown Stuart Nelson
• UK Primary Care Drug DictionaryUKCPRS (Secondary
  Care)Drug Ontology (OpenGALEN based)
• MEDDRA, FDA, Proprietary, , ,

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Unified Medical Language System (UMLS)

• Common reference point and link to MeSH Terms and
  literature
• De facto standard for universal identifiers
• Concept Unique Identifiers (CUIs)
• Lexical Unique Identifiers (LUIs)
• String Unique Identifiers (SUIs)
• Valuable in itselfHuge resource for mining and
  restructuring
• Udo Hahn and Stefan SchulzCoMMeT Conceptual
  Model of Medical Terminology
• http//www.coling.uni-freiburg.de/pub/schulz/comm
  et/
• Alexa McCray is speaking next