IMIA Working Group 6 Medical Concept Representation Focus of Meeting: Scientific developments: foundational issues rather than operational questions Scientific developments: foundational issues rather than operational questions New role of ontological research for new age of biomedical informatics New role of ontological research for new age of biomedical informatics Long-term view: ensure development of robust biomedical ontologies for the future Long-term view: ensure development of robust biomedical ontologies for the future

The Foundational Role of Anatomy for Biomedical Ontologies Cornelius Rosse M.D., D.Sc. S t r u c t u r a l I n f o r m a t i c s G r o u p University of Washington Cornelius Rosse M.D., D.Sc. S t r u c t u r a l I n f o r m a t i c s G r o u p University of Washington IMIA Working Group 6 Medical Concept Representation

What will be the take home message? What are the problems? If a science What is its theoretical foundation? What is its methodology? If a science What is its theoretical foundation? What is its methodology? We have established biomedical informatics Is it a service? Is it a new biomedical science? We have established biomedical informatics Is it a service? Is it a new biomedical science? Are theory and ontological methodology applied in the practice of biomedical informatics? Are theory and ontological methodology applied in the practice of biomedical informatics? How do applications of theory and methodology support inference about individuals (EHR)?

What will be the take home message? What are the solutions? Theoretical solution Propose a theory for biomedical reality derived from top-level ontologies Methodological solution Develop reference ontologies in domains of empirical basic biomedical science domains of empirical basic biomedical science using sound methodology using sound methodology Reuse reference ontologies in application ontologies designed for clinical specialties biomedical research education and training Theoretical solution Propose a theory for biomedical reality derived from top-level ontologies Methodological solution Develop reference ontologies in domains of empirical basic biomedical science domains of empirical basic biomedical science using sound methodology using sound methodology Reuse reference ontologies in application ontologies designed for clinical specialties biomedical research education and training

Case study: Cardiac Cycle

Atrial pressure

Case study: Cardiac Cycle Atrial pressure Left ventricular pressure

Case study: Cardiac Cycle Left ventricular volume Atrial pressure Left ventricular pressure

Case study: Cardiac Cycle Aortic pressure Atrial pressure Left ventricular volume Left ventricular pressure

Case study: Cardiac Cycle Aortic pressure Atrial pressure Left ventricular volume Left ventricular pressure

Case study: Cardiac Cycle Aortic pressure Atrial pressure Left ventricular volume Left ventricular pressure

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Case study: Cardiac Cycle Task: Generate ontological representation Resources extant terminologies: UMLS

Cardiac Cycle in UMLS

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Case study: Cardiac Cycle Task: Generate ontological representation of cardiac cycle Resources extant terminologies: UMLS textbooks, literature re-examination of cardiac cycle from ontological perspective

Diversion! Task: Generate ontological representation of cardiac cycle Resources extant terminologies: UMLS textbooks, literature re-examination of cardiac cycle from ontological perspective

Constitutents of Medical Science Basic sciences Clinical sciences

Constituents of Medical Science Basic sciences Clinical sciences PhysiologyInternal medicine PathologyPediatrics MicrobiologyPsychiatry BiochemistryAnesthesiology AnatomySurgery macroscopicgeneral surgery microscopicmaxillofacial surgery embryologyotolaryngology neuroanatomyneurosurgery

Basic Sciences Characteristics Concerned with canonical knowledge not data pertaining to individuals Concerned with canonical knowledge not data pertaining to individuals Taught/learned during first phase of professional training Taught/learned during first phase of professional training Do not target specialties in clinical medicine Need to be relearned in context of medical specialties Purpose Provide general understanding for reasoning and managing data pertaining to individuals Provide general understanding for reasoning and managing data pertaining to individuals

Basic Sciences Changing Environment 1960’s: curricular reform 1970’s: new biology

Basic Sciences Changing Environment 1960’s: curricular reform 1970’s: new biology Medicine Biomedicine; Biomedical science

Constituents of Biomedical Science Basic sciences Clinical sciences PhysiologyInternal medicine PathologyPediatrics MicrobiologyPsychiatry BiochemistryAnesthesiology AnatomySurgery macroscopicgeneral surgery microscopicmaxillofacial surgery embryologyotolaryngology neuroanatomyneurosurgery Traditional disciplines New biologyNew medicine molecular and cell biology molecular medicine molecular and cell biology molecular medicine genomics, proteomics regenerative medicine genomics, proteomics regenerative medicine developmental biology translational medicine developmental biology translational medicine systems biology nuclear medicine systems biology nuclear medicine

What is Biomedical Informatics? Basic sciences Clinical sciences PhysiologyInternal medicine PathologyPediatrics MicrobiologyPsychiatry BiochemistryAnesthesiology AnatomySurgery macroscopicgeneral surgery microscopicmaxillofacial surgery embryologyotolaryngology neuroanatomyneurosurgery Traditional disciplines New biologyNew medicine molecular and cell biology molecular medicine molecular and cell biology molecular medicine genomics, proteomics regenerative medicine genomics, proteomics regenerative medicine developmental biology translational medicine developmental biology translational medicine systems biology nuclear medicine systems biology nuclear medicine Biomedical Informatics Biomedical Informatics

What will be the take home message? What are the problems? If a science What is its theoretical foundation? What is its methodology? If a science What is its theoretical foundation? What is its methodology? We have established biomedical informatics Is it a service? Is it a new biomedical science? We have established biomedical informatics Is it a service? Is it a new biomedical science? Are theory and ontological methodology applied in the practice of biomedical informatics? Are theory and ontological methodology applied in the practice of biomedical informatics? How do applications of theory and methodology support inference about individuals (EHR)?

Attributes of Science Science has a.) theories on basis of which hypotheses can be formulated a.) theories on basis of which hypotheses can be formulated b.) methodology which can test the hypotheses b.) methodology which can test the hypotheses Best hope: Ontology

Need for theories and methodology What is ontology ? Smith (1996): “the science which deals with the nature and organization of reality” “the science which deals with the nature and organization of reality” Grenon, Smith & Goldberg (2004) “An ontology grasps the entities which exist within a given portion of the world at a given level of generality. It includes a taxonomy of the types of entities and relations that exist in that portion of the world seen from a given perspective.” “An ontology grasps the entities which exist within a given portion of the world at a given level of generality. It includes a taxonomy of the types of entities and relations that exist in that portion of the world seen from a given perspective.” Ontological theories derive from the philosophy of reality Ontological methodology creates an artifact which depicts a portion of the world creates an artifact which depicts a portion of the world seen from a given perspective

Need for theories and methodology What is ontology ? first meaning: first meaning: Smith (1996): “the science which deals with the nature and organization of reality “the science which deals with the nature and organization of reality Grenon, Smith & Goldberg (2004) “An ontology grasps the entities which exist within a given portion of the world at a given level of generality. It includes a taxonomy of the types of entities and relations that exist in that portion of the world seen from a given perspective.” “An ontology grasps the entities which exist within a given portion of the world at a given level of generality. It includes a taxonomy of the types of entities and relations that exist in that portion of the world seen from a given perspective.” second meaning: second meaning: an artifact an artifact projects to a given domain of reality projects to a given domain of reality created through the application of principles and methods of ontological science

Ambiguity -any domain discourse is full with it -humans are adapt at dealing with it - printed page tolerates it -computational inference will be crippled by it crippled by it Why base an ontology on reality?

Ambiguity -any domain discourse is full with it -humans are adapt at dealing with it - printed page tolerates it -computational inference will be crippled by it crippled by itConclusion: - we have to base ontology on reality - need to take a new look at reality Why base an ontology on reality?

What kinds of ontologies are there? 1. Formal, top-level ontologies 2. Domain reference ontologies 3. Terminology-based application ontologies

What kinds of ontologies are there? 1.Formal, top-level ontologies: DOLCE, BFO domain-independent theories framework of axioms and definitions framework of axioms and definitions high degree of representational accuracy designed to be used as controls on other types of ontologies

What kinds of ontologies are there? 1.Formal, top-level ontologies: DOLCE, BFO domain-independent theories framework of axioms and definitions framework of axioms and definitions high degree of representational accuracy designed to be used as controls on other types of ontologies 2. Domain reference ontologies: FMA declare a theory about a particular domain of reality make use of methods of top-level ontologies general purpose resources generalize to other domains anatomy generalizes to physiology, surgery anatomy generalizes to physiology, surgery

What kinds of ontologies are there? 1.Formal, top-level ontologies: DOLCE, BFO domain-independent theories framework of axioms and definitions framework of axioms and definitions high degree of representational accuracy designed to be used as controls on other types of ontologies 2. Domain reference ontologies: FMA declare a theory about a particular domain of reality make use of methods of top-level ontologies general purpose resources generalize to other domains anatomy generalizes to physiology, surgery anatomy generalizes to physiology, surgery 3. Terminology-based application ontologies: GO, other OBO, SNOMED, MeSH GO, other OBO, SNOMED, MeSH systems of terms purpose-built designed to meet particular needs annotating databases, medical data annotating databases, medical data

Basic Formal Ontology EntitiesOccurrentsContinuants Distinguishing criterion (differentia): Time

Entities Occurrents - SPAN entities Dependent entities which do not endure through time; unfold themselves in successive temporal phases (e.g., processes, actions) have temporal parts have temporal parts Basic Formal Ontology

Entities Occurrents - SPAN entities Dependent entities which do not endure through time; unfold themselves in successive temporal phases (e.g., processes, actions) have temporal parts have temporal parts Continuants- SNAP entities Entities which endure in toto in every instant of time at which they exist have spatial parts Independent continuants objects, components Dependent continuants attributes, roles, qualities, functions Basic Formal Ontology

END OF DIVERSION

Biological occurrent Biological entity Biological continuant is-a A theory of biomedical reality

Biological occurrent Extra-organismal biological continuant Extra-organismal biological continuant Biological entity Biological continuant Organismal continuant Organismal continuant is-a

Biological occurrent Independent organismal continuant Independent organismal continuant Dependent organismal continuant Dependent organismal continuant Extra-organismal biological continuant Extra-organismal biological continuant Biological entity Biological continuant Organismal continuant Organismal continuant is-a

Biological occurrent Independent organismal continuant Independent organismal continuant Dependent organismal continuant Dependent organismal continuant Extra-organismal biological continuant Extra-organismal biological continuant Material anatomical entity Material anatomical entity Material pathological entity Material pathological entity Biological entity Biological continuant Organismal continuant Organismal continuant Anatomical structure Canonical anatomical structure Variant anatomical structure Portion of canonical body substance Portion of blood Portion of cytosol Pathological structure Neoplasm Inflammatory structure Degenerated structure Portion of pathological body substance Portion of pus Portion of amyloid is-a

Biological occurrent Independent organismal continuant Independent organismal continuant Dependent organismal continuant Dependent organismal continuant Extra-organismal biological continuant Extra-organismal biological continuant Material anatomical entity Material anatomical entity Material pathological entity Material pathological entity Biological entity Immaterial anatomical continuant Immaterial anatomical continuant Physiological continuant Physiological continuant Immaterial pathological continuant Immaterial pathological continuant Biological continuant Organismal continuant Organismal continuant Anatomical structure Canonical anatomical structure Variant anatomical structure Portion of canonical body substance Portion of blood Portion of cytosol Pathological structure Neoplasm Inflammatory structure Degenerated structure Portion of pathological body substance Portion of pus Portion of amyloid Anatomical space Cavity of lysosome Anatomical surface E-face of plasma membrane Anatomical line Anatomical point Function Secrete Flex; Extend Physiological state Relaxed state Contracted state Physiological role Antagonist Pathological space Cavity of abscess Pathological surface Boundary of tumor Malfunction Atrial fibrillation Pathological state Malnutrition Pathological role is-a

Biological occurrent Independent organismal continuant Independent organismal continuant Dependent organismal continuant Dependent organismal continuant Extra-organismal biological continuant Extra-organismal biological continuant Material anatomical entity Material anatomical entity Material pathological entity Material pathological entity Biological entity Immaterial anatomical continuant Immaterial anatomical continuant Physiological continuant Physiological continuant Immaterial pathological continuant Immaterial pathological continuant Biological continuant Organismal continuant Organismal continuant Anatomical structure Canonical anatomical structure Variant anatomical structure Portion of canonical body substance Portion of blood Portion of cytosol Pathological structure Neoplasm Inflammatory structure Degenerated structure Portion of pathological body substance Portion of pus Portion of amyloid Anatomical space Cavity of lysosome Anatomical surface E-face of plasma membrane Anatomical line Anatomical point Function Secrete Flex; Extend Physiological state Systole Physiological role Antagonist Pathological space Cavity of abscess Pathological surface Boundary of tumor Malfunction Atrial fibrillation Pathological state Malnutrition Pathological role Organismal occurrent Organismal occurrent Extra-organismal biological occurrent Extra-organismal biological occurrent is-a

Biological occurrent Independent organismal continuant Independent organismal continuant Dependent organismal continuant Dependent organismal continuant Extra-organismal biological continuant Extra-organismal biological continuant Material anatomical entity Material anatomical entity Material pathological entity Material pathological entity Biological entity Immaterial anatomical continuant Immaterial anatomical continuant Physiological continuant Physiological continuant Immaterial pathological continuant Immaterial pathological continuant Biological continuant Organismal continuant Organismal continuant Anatomical structure Canonical anatomical structure Variant anatomical structure Portion of canonical body substance Portion of blood Portion of cytosol Pathological structure Neoplasm Inflammatory structure Degenerated structure Portion of pathological body substance Portion of pus Portion of amyloid Anatomical space Cavity of lysosome Anatomical surface E-face of plasma membrane Anatomical line Anatomical point Function Secrete Flex; Extend Physiological state Systole Physiological role Antagonist Pathological space Cavity of abscess Pathological surface Boundary of tumor Malfunction Atrial fibrillation Pathological state Malnutrition Pathological role Organismal occurrent Organismal occurrent Extra-organismal biological occurrent Extra-organismal biological occurrent Pathological process Pathological process Physiological process Physiological process Secreting Secreting insulin Transcribing RNA Mutating Metastasizing Necrosing is-a

Biological occurrent Independent organismal continuant Independent organismal continuant Dependent organismal continuant Dependent organismal continuant Extra-organismal biological continuant Extra-organismal biological continuant Material anatomical entity Material anatomical entity Material pathological entity Material pathological entity Biological entity Immaterial anatomical continuant Immaterial anatomical continuant Physiological continuant Physiological continuant Immaterial pathological continuant Immaterial pathological continuant Biological continuant Organismal continuant Organismal continuant Anatomical structure Canonical anatomical structure Variant anatomical structure Portion of canonical body substance Portion of blood Portion of cytosol Pathological structure Neoplasm Inflammatory structure Degenerated structure Portion of pathological body substance Portion of pus Portion of amyloid Anatomical space Cavity of lysosome Anatomical surface E-face of plasma membrane Anatomical line Anatomical point Function Secrete Flex; Extend Physiological state Systole Physiological role Antagonist Pathological space Cavity of abscess Pathological surface Boundary of tumor Malfunction Atrial fibrillation Pathological state Malnutrition Pathological role Organismal occurrent Organismal occurrent Extra-organismal biological occurrent Extra-organismal biological occurrent Pathological process Pathological process Physiological process Physiological process Secreting Secreting insulin Transcribing RNA Mutating Metastasizing Necrosing Ontology of Biomedical Reality (OBR) is-a

Definition: Material physical anatomical entity which has inherent 3D shape; generated by coordinated expression of the organism's own structural genes; Independent organismal continuant Independent organismal continuant Material anatomical entity Material anatomical entity Material pathological entity Material pathological entity Organismal continuant Organismal continuant Anatomical structure Theory of biological continuants

Body Part Body Part Human Body Human Body Organ System Organ System Organ Cell Organ Part Organ Part Portion of tissue Portion of tissue Anatomical Structure Anatomical Structure Cell Part Cell Part Biological Macromolecule Biological Macromolecule Acellular Anatomical Structure Acellular Anatomical Structure Theory of biological continuants

Material Physical Anatomical Entity Material Physical Anatomical Entity Body Part Body Part Human Body Human Body Organ System Organ System Organ Cell Organ Part Organ Part Portion of tissue Portion of tissue Anatomical Structure Anatomical Structure Portion of body substance Portion of body substance Cell Part Cell Part Biological Macromolecule Biological Macromolecule Acellular Anatomical Structure Acellular Anatomical Structure Theory of biological continuants

Material Physical Anatomical Entity Material Physical Anatomical Entity Body Part Body Part Human Body Human Body Organ System Organ System Organ Cell Organ Part Organ Part Portion of tissue Portion of tissue Anatomical Structure Anatomical Structure Portion of body substance Portion of body substance Cell Part Cell Part Biological Macromolecule Biological Macromolecule Acellular Anatomical Structure Acellular Anatomical Structure Independent organismal continuant Independent organismal continuant Theory of biological continuants

Material Physical Anatomical Entity Material Physical Anatomical Entity Body Part Body Part Human Body Human Body Organ System Organ System Organ Cell Organ Part Organ Part Portion of tissue Portion of tissue Anatomical Structure Anatomical Structure Portion of body substance Portion of body substance Cell Part Cell Part Biological Macromolecule Biological Macromolecule Acellular Anatomical Structure Acellular Anatomical Structure Independent organismal continuant Independent organismal continuant Non-material Physical Anatomical Entity Non-material Physical Anatomical Entity Space Surface Line Dependent organismal continuant Dependent organismal continuant Theory of biological continuants

Material Physical Anatomical Entity Material Physical Anatomical Entity Body Part Body Part Human Body Human Body Organ System Organ System Organ Cell Organ Part Organ Part Portion of tissue Portion of tissue Anatomical Structure Anatomical Structure Portion of body substance Portion of body substance Cell Part Cell Part Biological Macromolecule Biological Macromolecule Acellular Anatomical Structure Acellular Anatomical Structure Independent organismal continuant Independent organismal continuant Non-material Physical Anatomical Entity Non-material Physical Anatomical Entity Space Surface Line Dependent organismal continuant Dependent organismal continuant FMA: created with ontological methods

Ontological methods

Somatic cell which has as direct parts of its cytoplasm myofibrils organized in various patterns.

Muscle cell which has as its direct parts myofilaments organized into sarcomeres.

Striated muscle cell which has as its direct parts one or two centrally placed nuclei.

Continuants in Cardiac Cycle Participants Biatrial part of heart Biventricular part of heart

Fibrous pericardium Pericardial cavity How do we represent pathological continuants?

Will the processes remain normal?

Can we propose a theory of biological processes? Rationale for theory of continuants: based on gene expression of dependent continuants compatible with theory of OBR Rationale for theory of processes: need to formulate a hypothesis evaluate it through instantiation of physiological and pathological processes

Can we propose a theory of biological processes? A process is an occurrent which is realized through the conversion of physical energy of one kind to another or to a change in structural order. Start with a hypothesis:

Theory of biological processes A process is an occurrent which is realized through the conversion of physical energy of one kind to another or to a change in structural order. Hypothesis: Rationale: processes involve movement of their participants caused by some force generated by dissipation of energy

Where is energy generated?

Sarcomere

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Sarcomere Ca++

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Conversion of energy from one kind to another Liberated energy Conversion of chemical to mechanical energy Molecular conformational change

Transmission of force by participants in cardiac cycle Macromolecule

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OPERATORS

How do we classify processes? Process is - an occurrent which is realized through the conversion of physical energy of one kind to another or to a change in structural order - a transformation of one state of an occurrent into another state. - a change in the values of the set of attributes that define a state. Definition

How do we classify processes? Process is - an occurrent which is realized through the conversion of physical energy of one kind to another or to a change in structural order. - a transformation of one state of an occurrent into another state. - a change in the values of the set of attributes that define a state State is a dependent continuant specified by the values of a set of attributes. Definition

How do we classify processes? Process is - an occurrent which is realized through the conversion of physical energy of one kind to another or to a change in structural order. - a transformation of one state of an occurrent into another state. - a change in the values of the set of attributes that define a state State is a dependent continuant specified by the values of a set of attributes A biological process is a process the direct participants of which are one or more anatomical entities Definition

Can OBR accommodate constituents of cardiac cycle? Biological occurrent Organismal occurrent Organismal occurrent Extra-organismal biological occurrent Extra-organismal biological occurrent Pathological process Pathological process Physiological process Physiological process Need to deal with non-biological participants non-biological participantsCa++ non-biological processes chemical bonding and bond breaking attributes and operators generalize to non-biological domains Laws of physics and chemistry operate in biological and non-biological domains of reality

Conflict with OBR Biological occurrent Organismal occurrent Organismal occurrent Extra-organismal biological occurrent Extra-organismal biological occurrent Pathological process Pathological process Physiological process Physiological process Need to deal with non-biological participants non-biological participantsCa++ non-biological processes chemical bonding and bond breaking attributes and operators generalize to non-biological domains Laws of physics and chemistry operate in biological and non-biological domains of reality OBR hypothesis must be modified

Acyclic process How do we classify processes? Process Cyclic process

Acyclic process Myosin-actin binding-unbinding Myosin-actin binding-unbinding Myosin head flexure-unflexure Myosin head flexure-unflexure How do we classify processes? Process Cyclic process Calcium-troponin binding-unbinding Calcium-troponin binding-unbinding Sliding of myofilaments Sliding of myofilaments Shortening of sarcomere Shortening of sarcomere Contraction myocyte myocardial loop Contraction myocyte myocardial loop Increase in LV blood pressure Increase in LV blood pressure Flowing of LV blood to aorta Flowing of LV blood to aorta Cardiac cycling

Acyclic process Chemical-to- chemical energy Chemical-to- chemical energy Molecular conformational change Molecular conformational change Myosin-actin binding-unbinding Myosin-actin binding-unbinding Myosin head flexure-unflexure Myosin head flexure-unflexure How do we classify processes? Process Cyclic process Chemical-to- mechanical energy Chemical-to- mechanical energy Calcium-troponin binding-unbinding Calcium-troponin binding-unbinding Mechanical-to- mechanical energy Mechanical-to- mechanical energy Sliding of myofilaments Sliding of myofilaments Shortening of sarcomere Shortening of sarcomere Contraction myocyte myocardial loop Contraction myocyte myocardial loop Mechanical-to- fluid potential energy Mechanical-to- fluid potential energy Increase in LV blood pressure Increase in LV blood pressure Flowing of LV blood to aorta Flowing of LV blood to aorta Fluid potential-to- fluid kinetic energy Fluid potential-to- fluid kinetic energy Chemical-to- fluid dynamic energy Chemical-to- fluid dynamic energy Cardiac cycling

How do we classify processes?

Testing the ‘Process’ hypothesis A process is an occurrent which is realized through the conversion of physical energy of one kind to another or to a change in structural order. Hypothesis: Rationale: processes involve movement of their participants caused by some force generated by dissipation of energy Testing of hypothesis: rooted in non-equilibrium thermodynamics first classification trial yields results intuitive at the operational level conform to single inheritance

How do we classify non-biological entities?

How do we classify physical attributes?

How do we classify operators?

Fibrous pericardium Pericardial cavity How do we represent pathological pathological processes?

Biological occurrent Independent organismal continuant Independent organismal continuant Dependent organismal continuant Dependent organismal continuant Extra-organismal biological continuant Extra-organismal biological continuant Material anatomical entity Material anatomical entity Material pathological entity Material pathological entity Biological entity Immaterial anatomical continuant Immaterial anatomical continuant Physiological continuant Physiological continuant Immaterial pathological continuant Immaterial pathological continuant Biological continuant Organismal continuant Organismal continuant Anatomical structure Canonical anatomical structure Variant anatomical structure Portion of canonical body substance Portion of blood Portion of cytosol Pathological structure Neoplasm Inflammatory structure Degenerated structure Portion of pathological body substance Portion of pus Portion of amyloid Anatomical space Cavity of lysosome Anatomical surface E-face of plasma membrane Anatomical line Anatomical point Function Secrete Flex; Extend Physiological state Systole Physiological role Antagonist Pathological space Cavity of abscess Pathological surface Boundary of tumor Malfunction Atrial fibrillation Pathological state Malnutrition Pathological role Organismal occurrent Organismal occurrent Extra-organismal biological occurrent Extra-organismal biological occurrent Pathological process Pathological process Physiological process Physiological process Secreting Secreting insulin Transcribing RNA Mutating Metastasizing Necrosing Ontology of Biomedical Reality (OBR) is-a

Physical occurrent Entity of Physical Reality Entity of Physical Reality Physical continuant Process Dimensional continuant Dimensional continuant Non-dimensional continuant Non-dimensional continuant Spatio- temporal worm Spatio- temporal worm

Physical occurrent Entity of Physical Reality Entity of Physical Reality Physical continuant Process Dimensional continuant Dimensional continuant Immaterial dimensional continuant Immaterial dimensional continuant Biological material continuant Non-biological material continuant Material dimensional continuant Material dimensional continuant Non-biological immaterial continuant Biological immaterial continuant Non-dimensional continuant Non-dimensional continuant Spatio temporal worm Spatio temporal worm

Physical occurrent Entity of Physical Reality Entity of Physical Reality Physical continuant Process Dimensional continuant Dimensional continuant Immaterial dimensional continuant Immaterial dimensional continuant Biological material continuant Non-biological material continuant Material dimensional continuant Material dimensional continuant Non-biological immaterial continuant Biological immaterial continuant Non-dimensional continuant Non-dimensional continuant Attribute Operator Structural operator Attribute operator Biological operator Material attribute Process attribute Spatial attribute State Function Role Spatio temporal worm Spatio temporal worm

Physical occurrent Entity of Physical Reality Entity of Physical Reality Physical continuant Process Cyclic process Acyclic process Dimensional continuant Dimensional continuant Immaterial dimensional continuant Immaterial dimensional continuant Biological material continuant Non-biological material continuant Material dimensional continuant Material dimensional continuant Non-biological immaterial continuant Biological immaterial continuant Non-dimensional continuant Non-dimensional continuant Attribute Operator Structural operator Attribute operator Biological operator Material attribute Process attribute Spatial attribute State Function Role Spatio- temporal worm Spatio- temporal worm Cardiac cycling Kreb’s cycle Control process Morphogenetic process Replication process Degeneration process Ontology of Physical Reality (OPR)

Physical occurrent Entity of Physical Reality Entity of Physical Reality Physical continuant Process Cyclic process Acyclic process Dimensional continuant Dimensional continuant Immaterial dimensional continuant Immaterial dimensional continuant Biological material continuant Non-biological material continuant Material dimensional continuant Material dimensional continuant Non-biological immaterial continuant Biological immaterial continuant Non-dimensional continuant Non-dimensional continuant Attribute Operator Structural operator Attribute operator Biological operator Material attribute Process attribute Spatial attribute State Function Role Spatio temporal worm Spatio temporal worm Cardiac cycle Kreb’s cycle Control process Morphogenetic process Replication process Degeneration process Ontology of Physical Reality (OPR) Anatomical Structure

What about our case study: Cardiac Cycle?

Protégé a physiological-chemical to fluid kinetic energy change which has as its direct anatomical participants the heart and the portion of blood in the heart

What will be the take home message? What are the problems? If biomedical informatics is to be a science What is the theoretical foundation? What is its methodology? If biomedical informatics is to be a science What is the theoretical foundation? What is its methodology? We have established biomedical informatics Is it a service? Is it a new biomedical science? We have established biomedical informatics Is it a service? Is it a new biomedical science? Are theory and ontological methodology applied in the practice of biomedical informatics? Are theory and ontological methodology applied in the practice of biomedical informatics? How do applications of theory and methodology support inference about individuals (EHR)?

Basic Sciences Characteristics Concerned with canonical knowledge not data pertaining to individuals Concerned with canonical knowledge not data pertaining to individuals Taught/learned during first phase of professional training Taught/learned during first phase of professional training Do not target specialties in clinical medicine Need to be relearned in context of medical specialties Purpose Provide general understanding for reasoning and managing data pertaining to individuals Provide general understanding for reasoning and managing data pertaining to individuals

What kinds of ontologies are there? 1. Formal, top-level ontologies 2. Domain reference ontologies 3. Terminology-based application ontologies

What will be the take home message? What are the solutions? Theoretical solution Propose a theory for biomedical reality derived from top-level ontologies Methodological solution Develop reference ontologies in domains of empirical basic biomedical science using sound methodology using sound methodology Reuse reference ontologies in application ontologies designed for clinical specialties biomedical research education and training Theoretical solution Propose a theory for biomedical reality derived from top-level ontologies Methodological solution Develop reference ontologies in domains of empirical basic biomedical science using sound methodology using sound methodology Reuse reference ontologies in application ontologies designed for clinical specialties biomedical research education and training

Attribute Operator Material or Spatial Attribute Structural operator Biological operator Process Attribute Dimensional continuant Process Attribute Continuant Operator Process Need for dynamically defining disciplinary boundaries

Traditional basic science: anatomy Attribute Operator Material or Spatial Attribute Structural operator Biological operator Process Attribute Dimensional continuant Process Attribute Continuant Operator Process

Traditional basic science: Physiology and Pathophysiology Attribute Operator Material or Spatial Attribute Structural operator Biological operator change attribute values has participants has role-player attributes has attributes has part Process Attribute has attribute Dimensional continuant create or destroy create or destroy Process Attribute Continuant Operator Process

The Foundational Role of Anatomy for Biomedical Ontologies Cornelius Rosse M.D., D.Sc. S t r u c t u r a l I n f o r m a t i c s G r o u p University of Washington Cornelius Rosse M.D., D.Sc. S t r u c t u r a l I n f o r m a t i c s G r o u p University of Washington IMIA Working Group 6 Medical Concept Representation