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

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.

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.

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.

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?

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.

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)

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

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

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

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

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

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?

Anatomy ontology: Kinds of anatomical concepts Adapted from Bloom & Fawcett: 1994 12th ed Chapman & Hall

Representation of Anatomical Entities

Representation of Anatomical Entities

Representation of Anatomical Entities

Representation of Anatomical Entities

Representation of Anatomical Entities

Representation of Anatomical Entities

Representation of Anatomical Entities

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?

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.

Anatomical Entity

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

Anatomical Entity Physical Anatomical Entity -is a- Conceptual

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

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

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

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

Implementation of FM in Protégé 2000

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.

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

Experiments in Cell Classification

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

Experiments in Cell Classification

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

Experiments in Cell Classification

Frame of Cell

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

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

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

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

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

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 )

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 )

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 )

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

ASA of Cell Generic cell Specialized cell Skeletal muscle fiber

Parts of the Cell

Parts of the Cell

Parts of the Cell

Parts of the Cell

Parts of the Cell

Frame of Cell

Cell-Specific Attributes

Cell-Specific Attributes

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?

Organ Modeling Scenario Generic cell Satellite cell Skeletal muscle fiber

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

Myogenic Lineage

Myogenic Lineage

Myogenic Lineage Gives rise to

Myogenic Lineage Gives rise to Gives rise to

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

Myogenic Lineage Myosin

Myogenic Lineage Myf5, MyoD Myf5 Myogenin Myosin

Myogenic Lineage Myf5, MyoD Myf5 Myogenin Myosin Myogenin Myosin

Organ Modeling Scenario Generic cell Satellite cell Skeletal muscle fiber

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?

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

Myogenic Lineage Myf5, MyoD Myf5 Myogenin Myosin Myogenin Myosin

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

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)?

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

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

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

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

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

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

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.