2. Towards a Unified Ontology for Biomedical Modeling and Simulation
Digital Human:
Towards a Unified Ontology for Biomedical Modeling and Simulation
The Potential of the Digital Anatomist Foundational Model for “Unifying” Biomedical Ontologies Cornelius Rosse M.D., D.Sc. Structural Informatics Group University of Washington

3. in Structural Informatics Research
Motivation
in Structural Informatics Research
Role of structure in biomedical concept representation
Manifestations of health and disease are conceptualized as attributes of anatomical structures.

4. in Structural Informatics Research
Motivation
in Structural Informatics Research
Role of structure in biomedical concept representation
Manifestations of health and disease are conceptualized as attributes of anatomical structures.
Logical and comprehensive representation of anatomical knowledge provides
a foundation for other types of biomedical information.

5. Towards a Unified Ontology for Biomedical Modeling and Simulation
Digital Human:
Towards a Unified Ontology for Biomedical Modeling and Simulation
Hypothesis Correlation (“unification”) of diverse biomedical ontologies is best accomplished by mapping structural attributes of anatomical entities.

6. Agenda of talk What is the Foundational Model?
What kind of information does it represent?
How does it represent it?
How can it support organ modeling and simulation?

7. What is the Foundational Model (FM)?
The Digital Anatomist Foundational Model
is a symbolic model of the physical organization of the human body;
declares the principles
for including concepts and relationships
that are implicitly assumed
when knowledge of anatomy
is applied in different contexts;
explicitly defines
concepts and relationships
necessary and sufficient for consistently
modeling the structure of the
human body.

8. Fm = (Ao, ASA, ATA, Mk) What is the Foundational Model (FM)?
High Level Scheme
Fm = (Ao, ASA, ATA, Mk)
where:
Ao = Anatomy ontology
ASA = Anatomical Structural Abstraction
ATA = Anatomical Transformation Abstraction
Mk = Metaknowledge
(principles, rules, axioms)

9. Anatomical Structural Abstraction
FM = (Ao, ASA, ATA, Mk)
ASA
Anatomical Structural Abstraction Do
Dimensional
ontology Bn
Boundary
network Pn
Part of
SAn
Spatial Association Ln
Location network On
Orientation network Cn
Connectivity network
CTMn
Containment
network
AJn
Adjacency
QCn
Qualitative
Coordinate
CTn
Continuity
network
ATn
Attachment
SYn
Synaptic
Connectivity

10. Implementation of High Level Scheme
Principled Modeling =
Foundational Principles + Explicit Definitions
and
Knowledge modeling environment:
Protégé-2000

11. Principled Modeling Foundational Principles Definition principle
Assertions that provide the basis for reasoning and action
Unified context principle
Definition principle
Constitutive principle
Organizational unit principle

12. Principled Modeling Explicit Definitions Purpose of FM definitions:
Specify the essence of anatomical entities
in terms of two sets of structural attributes:
those of their genus
differentia
Provide the rationale for an inheritance hierarchy
in a structural context

13. Principled Modeling Foundational Principles Definition principle
Assertions that provide the basis for reasoning and action
Unified context principle
Definition principle
Constitutive principle
Organizational unit principle

14. Agenda of talk What is the Foundational Model?
What kind of information does it represent?
How does it represent it?
How can it support organ modeling and simulation?

15. Anatomy ontology: Kinds of anatomical concepts Adapted from
Bloom & Fawcett: th ed
Chapman & Hall

16. Representation of
Anatomical Entities

17. Representation of
Anatomical Entities

18. Representation of
Anatomical Entities

19. Representation of
Anatomical Entities

20. Representation of
Anatomical Entities

21. Representation of
Anatomical Entities

22. Representation of
Anatomical Entities

23. Agenda of talk What is the Foundational Model?
What kind of information does it represent?
How does it represent it?
How can it support organ modeling and simulation?

24. Ao: taxonomic classification based on
Principled Modeling
Fm = (Ao, ASA, ATA, Mk)
Ao: taxonomic classification based on
explicit definition of concepts,
inheritance of definitional
structural attributes;
consistent with foundational principles.

25. Anatomical Entity

26. Anatomical Entity
Biological entity, which forms the whole or a part of, or is an attribute of, the structural organization of a biological organism.

27. Anatomical Entity
Physical
Anatomical Entity
-is a-
Conceptual

28. Non-material Physical
Anatomical Entity
-is a-
Physical
Anatomical Entity
Conceptual
Anatomical Entity
Material Physical
Anatomical Entity
Non-material Physical

29. Non-material Physical
Anatomical Entity
-is a-
Physical
Anatomical Entity
Conceptual
Anatomical Entity
Material Physical
Anatomical Entity
Non-material Physical
Anatomical Entity
Anatomical
Space
Anatomical
Surface
Anatomical
Line
Anatomical
Point

30. Non-material Physical
Anatomical Entity
-is a-
Physical
Anatomical Entity
Conceptual
Anatomical Entity
Material Physical
Anatomical Entity
Non-material Physical
Anatomical Entity
Body
Substance
Anatomical
Structure

31. Non-material Physical
Anatomical Entity
-is a-
Physical
Anatomical Entity
Conceptual
Anatomical Entity
Material Physical
Anatomical Entity
Non-material Physical
Anatomical Entity
Body
Substance
Anatomical
Structure
Cell
Body
Part
Human
Organ
System
Organ
Organ
Part
Tissue
Organ component
Organ subdivision

32. Implementation of FM
in Protégé 2000

33. Implementation of FM in Protégé 2000
Material physical anatomical entity which has inherent 3D shape; is generated by coordinated expression of the organism's own structural genes.

34. Implementation of FM in Protégé 2000
Anatomical structure that consists of cytoplasm surrounded by a plasma membrane, with or without the cell nucleus.

35. Experiments in Cell Classification

36. Experiments in Cell Classification
Somatic cell which has intercellular junctions with homologous cells.

37. Experiments in Cell Classification

38. Experiments in Cell Classification
Somatic cell which has adhesion sites with extracellular matrix components.

39. Experiments in Cell Classification

40. Frame of Cell

41. Anatomical Structural Abstraction
FM = (Ao, ASA, ATA, Mk)
ASA
Anatomical Structural Abstraction

42. Anatomical Structural Abstraction
FM = (Ao, ASA, ATA, Mk)
ASA
Anatomical Structural Abstraction Do
Dimensional
ontology Bn
Boundary
network Pn
Part of
SAn
Spatial Association

43. Anatomical Structural Abstraction
FM = (Ao, ASA, ATA, Mk)
ASA
Anatomical Structural Abstraction Do
Dimensional
ontology Bn
Boundary
network Pn
Part of
SAn
Spatial Association Ln
Location network On
Orientation network Cn
Connectivity network

44. Anatomical Structural Abstraction
FM = (Ao, ASA, ATA, Mk)
ASA
Anatomical Structural Abstraction Do
Dimensional
ontology Bn
Boundary
network Pn
Part of
SAn
Spatial Association Ln
Location network On
Orientation network Cn
Connectivity network
CTMn
Containment
network
AJn
Adjacency
QCn
Qualitative
Coordinate

45. Anatomical Structural Abstraction
FM = (Ao, ASA, ATA, Mk)
ASA
Anatomical Structural Abstraction Do
Dimensional
ontology Bn
Boundary
network Pn
Part of
SAn
Spatial Association Ln
Location network On
Orientation network Cn
Connectivity network
CTMn
Containment
network
AJn
Adjacency
QCn
Qualitative
Coordinate
CTn
Continuity
network
ATn
Attachment
CCn
Cell
Connectivity

46. ASA = ( Do, Pn, Bn, SAn ) Dimensional Ontology Anatomy Ontology Right
Polyhedron
Volume (3-D)
Dimensional
Ontology
Cardiac
Chamber
Organ
Subdivision
Organ Part
Anatomical Structure
Anatomy Ontology
-is a-
Right
Ventricle
ASA = ( Do, Pn, Bn, SAn )

47. ASA = ( Do, Bn, Pn, SAn ) Dimensional Ontology Anatomy Ontology
Polyhedron
Volume (3-D)
Dimensional
Ontology
Cardiac
Chamber
Organ
Subdivision
Organ Part
Anatomical Structure
Anatomy Ontology
-is a-
Sternocostal
Surface
Diaphragmatic
bounded by
boundary of
Anatomical
Surface (2-D)
Right
Coronary
Sulcus
Anterior
Interventricular
Line (1-D)
Inferior margin
of heart
Apex
Boundary Network
-is a-
Posterior
IV Sulcus
Crux of heart
Landmark
Point (1-D)
Right
Ventricle
ASA = ( Do, Bn, Pn, SAn )

48. ASA = ( Do, Bn, Pn, SAn ) Dimensional Ontology Anatomy Ontology
Polyhedron
Volume (3-D)
Dimensional
Ontology
Cardiac
Chamber
Organ
Subdivision
Organ Part
Anatomical Structure
Anatomy Ontology
-is a-
Sternocostal
Surface
Diaphragmatic
bounded by
boundary of
Anatomical
Surface (2-D)
Right
Coronary
Sulcus
Anterior
Interventricular
Line (1-D)
Inferior margin
of heart
Apex
Boundary Network
-is a-
Posterior
IV Sulcus
Crux of heart
Landmark
Point (1-D)
Part-of
Network
Heart
super-
object
Inflow part
of RV
Infundibulum
Wall of RV
Cavity of RV
subobject
-is a-
has
Cavity of
infund.
infl.part
Right
Ventricle
ASA = ( Do, Bn, Pn, SAn )

49. ASA = ( Do, Bn, Pn, SAn ) Dimensional Ontology Anatomy Ontology
Polyhedron
Volume (3-D)
Dimensional
Ontology
Cardiac
Chamber
Organ
Subdivision
Organ Part
Anatomical Structure
Anatomy Ontology
-is a-
Sternocostal
Surface
Diaphragmatic
bounded by
boundary of
Anatomical
Surface (2-D)
Right
Coronary
Sulcus
Anterior
Interventricular
Line (1-D)
Inferior margin
of heart
Apex
Boundary Network
-is a-
Posterior
IV Sulcus
Crux of heart
Landmark
Point (1-D)
Part-of
Network
Heart
super-
object
Inflow part
of RV
Infundibulum
Wall of RV
Cavity of RV
subobject
-is a-
has
Cavity of
infund.
infl.part
ASA = ( Do, Bn, Pn, SAn )
Right
Ventricle
has
adjacency
anterior
inferior
to left
Left
ventricle
Pericardial
sac
Diaphragm
Spatial Association Network

50. ASA of Cell
Generic cell
Specialized cell
Skeletal
muscle fiber

51. Parts of the Cell

52. Parts of the Cell

53. Parts of the Cell

54. Parts of the Cell

55. Parts of the Cell

56. Frame of Cell

57. Cell-Specific Attributes

58. Cell-Specific Attributes

59. Agenda of talk What is the Foundational Model?
What kind of information does it represent?
How does it represent it?
How can it support
organ modeling and simulation?

60. Organ Modeling Scenario
Generic cell
Satellite
cell
Skeletal
muscle fiber

61. Muscle-specific cell markers
Myogenic Lineage
Muscle-specific cell markers
Terminally differentiated cell: Myosin
Muscle progenitor cells:
Muscle-specific transcription factors:
Myf5
MyoD
Myogenin

62. Myogenic Lineage

63. Myogenic Lineage

64. Myogenic Lineage
Gives rise to

65. Myogenic Lineage
Gives rise to
Gives rise to

66. Myogenic Lineage Embryonic stem cell Blood-borne stem cell Myogenic
(Satellite cell)
Myoblast
Myocyte
Fuses
Immature myotube
Skeletal muscle fiber

67. Myogenic Lineage
Myosin

68. Myogenic Lineage
Myf5, MyoD
Myf5
Myogenin
Myosin

69. Myogenic Lineage Myf5, MyoD Myf5 Myogenin Myosin Myogenin Myosin

70. Organ Modeling Scenario
Generic cell
Satellite
cell
Skeletal
muscle fiber

71. Agenda of talk What is the Foundational Model?
What kind of information does it represent?
How does it represent it?
How can it support
alignment (“unification”) of ontologies?

72. ASA = ( Do, Bn, Pn, SAn ) Dimensional Ontology Anatomy Ontology
Polyhedron
Volume (3-D)
Dimensional
Ontology
Cardiac
Chamber
Organ
Subdivision
Organ Part
Anatomical Structure
Anatomy Ontology
-is a-
Sternocostal
Surface
Diaphragmatic
bounded by
boundary of
Anatomical
Surface (2-D)
Right
Coronary
Sulcus
Anterior
Interventricular
Line (1-D)
Inferior margin
of heart
Apex
Boundary Network
-is a-
Posterior
IV Sulcus
Crux of heart
Landmark
Point (1-D)
Part-of
Network
Heart
super-
object
Inflow part
of RV
Infundibulum
Wall of RV
Cavity of RV
subobject
-is a-
has
Cavity of
infund.
infl.part
ASA = ( Do, Bn, Pn, SAn )
Right
Ventricle
has
adjacency
anterior
inferior
to left
Left
ventricle
Pericardial
sac
Diaphragm
Spatial Association Network

73. Myogenic Lineage Myf5, MyoD Myf5 Myogenin Myosin Myogenin Myosin

74. Anatomical Structural Abstraction
FM = (Ao, ASA, ATA, Mk)
ASA
Anatomical Structural Abstraction Do Bn Pn
SAn
Dimensional
ontology
Boundary
network
Part_of
network
Spatial Association
network Ln On Cn
Location network
Orientation network
Connectivity network
CTMn
AJn
QCn
CTn
ATn
SYn
Containment
network
Adjacency
network
Qualitative
Coordinate
network
Continuity
network
Attachment
network
Synaptic
Connectivity
network

75. Agenda of talk What is the Foundational Model?
What kind of information does it represent?
How does it represent it?
How can it support
experiment management systems (EMS)?

76. Digital Anatomist Information System
Anatomy Knowledge Sources DA
Foundational
Model
Image
Repository

77. Digital Anatomist Information System
Network
Authoring
Programs
End-User
Programs
Servers DA
Foundational
Model
Image
Repository
Anatomy Knowledge Sources

78. Digital Anatomist Information System
End User Interfaces
Network
Authoring
Programs
Digital
Anatomist
Atlases
Brain
Mapper
EMS
Servers DA
Foundational
Model
Image
Repository

79. Digital Anatomist Information System
DB(1)
DB(2)
DB(n)
Network
Authoring
Programs
EMS(n)
EMS(1)
EMS(2)
Servers DA
Foundational
Model
Image
Repository

80. Conclusions
Fm = (Ao, ASA, ATA, Mk)

81. FmBODY = {FmANATOMICAL_ENTITY}
Conclusions
Fm = (Ao, ASA, ATA, Mk)
FmBODY = {FmANATOMICAL_ENTITY}

82. Conclusions Role of Foundational Model of Anatomy
Prototype for symbolic models in other domains
e.g., physiology, pathology, cancer therapy
Core of biomedical knowledge bases
to solve problems in education, research, health care
Align (“unify”) diverse biomedical ontologies
"Foundational" because
anatomy is fundamental to all
biomedical sciences;
anatomical concepts encompassed by FM
generalize to all biomedical domains.