2. Interest in "ontologies": Neuroinfromatics Working Group February 2001 meetings February 2001 meetings HBP PIs HBP PIs Neuroanatomy Ontology Workshop Neuroanatomy Ontology Workshop Human Brain Project

3. Neuroanatomy Ontology should Expectations: Neuroanatomy Ontology should "Index and retrieve neuroscience information by species for mouse, rat, macaque, human; Define several hierarchical schemes for grouping primary structures to support accessing information in bigger chunks; Specify the relation of several thousand synonyms to allow the retrieval of information in terms of different nomenclatures; Provide atlases of segmented coronal brain sections for warping of MRI and PET scans." Neuroanatomy Ontology Workshop Summary

4. Explaining the Brain to a Computer Cornelius Rosse M.D., D.Sc., Structural Informatics Group University of Washington Mark S. Tuttle Ph.D., Apelon Federal Services, Inc.

5. Goals: Why we need to explain the brain to a computer? What to explain about the brain to a computer? How to do it? How to do it? What uses will it have? Explaining the Brain to a Computer

6. Why to explain the Brain to a Computer? "Few researchers use existing ontologies; why do another one that no one will use?" why do another one that no one will use?" Neuroanatomy Ontology Workshop Summary ”Why do we need a standard taxonomy? May disenfranchise a substantial user community." "Neuro-ontology development is an ill-posed problem.” HBP PIs' question/comment

7. Why to explain the Brain to a Computer? Prototype problem: Cortical language mapping Human Brain Project grant: Structural Information Framework for Brain Mapping J.F. Brinkley PI.

8. Superior temporal gyrus Cortical language mapping

9. Locations tested Active language site Intra-operative language sites

10. Supramarginal gyrus Variant gyral pattern Variant gyri

11. Cortical language sites Intra-operative language sites

12. Functional MRI language sites

13. Superimposed FMRI and cortical language maps

14. recorded with surface coordinate system of Caviness et al Incidence of cortical language sites

15. Montreal Average Brain All Male Patients N=15

16. Why to explain the Brain to a Computer? Graphical models: Document existence of probabilistic structure /function correlations Cannot reveal nature of relationships meaning of relationships Requirement: Add meaning to graphical data Symbolic Model

17. Why to explain the Brain to a Computer? Symbolic model to empower the computer to make inferences about the brain; to support knowledge-based applications for addressing neuroscience problems.

18. Goals: Why we need to explain the brain to a computer? What to explain about the brain to a computer? How to do it? How to do it? What uses will it have? Explaining the Brain to a Computer

19. What to explain about the brain to a computer? "What is the knowledge we need to classify?" "What levels of knowledge are to be included?" "Explicit definition of domain of neuroscience is a daunting task." HBP PIs' question/comments

20. What to explain about the brain to a computer? Two key strategic issues: 1. Constraints 2. Priorities

21. What Constraints? Subdomains in language mapping problem at UW: Neuroanatomy Richard Martin Kate Mulligan Neuroradiology Ken Maravilla Neurosurgery George Ojemann Psychology David Corina Karen Kinbar

22. What Constraints? Subdomains in language mapping problem at UW: Neuroanatomy Structural Informatics Richard MartinGraphical modeling Kate MulliganAndrew Poliakov, Jeff Prothero, Kevin Hinshaw Neuroradiology Symbolic modeling Ken MaravillaCornelius Rosse, Richard Martin, Jose Mejino, Linda Shapiro NeurosurgeryDatabase George OjemannRex Jakobovits PsychologyInformation System design David CorinaJim Brinkley Karen Kinbar

23. What Priorities? Motivation for Structural Informatics: Manifestations of health and disease may be regarded as attributes of anatomical structures; Logical and consistent representation of anatomical structure can provide the foundation for organizing other biomedical information.

24. What Priorities? "Any integrative approach by necessity will require a neuroanatomical basis" "Neuroanatomical ontology should provide the logical framework for organizing and locating information about the brain." organizing and locating information about the brain." Neuroanatomy Ontology Workshop Summary

25. What is anatomy? "Anatomy" …….. a homonym for anatomy (structure) e.g., anatomy of the frog, hand, brain anatomy (science) systematized branch of knowledge accumulated about anatomy (structure).

26. What is structure? "Structure" ……. a homonym for something composed of parts; (e.g., a building, a cell, a plant, brain) i.e., a material object the arrangement or interrelation of all the parts of a whole. (e.g., of a sentence, a symphony, or of society, government, or of the atom, the hand) i.e., relationships

27. What is structure? Structure of a material object Structure of Structure = Subobjects (parts) + Structural Relationships The components of an object and their manner of arrangement in constituting a whole.

28. What is anatomical structure? ”Anatomical Structure" … a homonym for a material object generated by the coordinated expression of an organism's own structural genes; the arrangement (physical interrelation) of all the parts of an anatomical structure in constituting the whole. Synonym: 'biological structure'

29. What Priorities? Question: What to explain first about the brain to a computer? Answer: The structure of anatomical structures that constitute the brain. Structure Brain = ({Subobject Brain }, {Structural relationship Brain })

30. What Priorities? Question: What to enter in the computer to explain (model) the structure of the brain? Answer: Symbols for anatomical structures of the brain. Symbols for structural relationships within the brain.

32. What kind of symbols? Thought “Concept” Symbol “Term” Referent Triangle of Meaning

33. What is a symbolic model? Symbolic model, a conceptualization of a domain of discourse represented with non-graphical symbols; in computer-processible (“understandable”) form; supports inference (reasoning).

34. What is a foundational model? Foundational Model is a symbolic model; declares the principles for including concepts and relationships that are implicitly assumed when knowledge of the domain is applied in different contexts; explicitly defines concepts and relationships necessary and sufficient for consistently modeling the structure of the coherent knowledge domain.

35. What is the Foundational Model of Anatomy (FM)? Foundational Model of Anatomy 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.

36. What is the Foundational Model of Anatomy (FM)? A symbolic model of anatomy (science) represents the physical organization (structure) of biological organisms; currently limited to the human body. "Foundational" because anatomy is fundamental to all biomedical sciences; anatomical concepts encompassed by FM generalize to all biomedical domains.

37. where: Ao= Anatomy ontology ASA= Anatomical Structural Abstraction ATA= Anatomical Transformation Abstraction Mk= Metaknowledge (principles, rules, axioms) where: Ao= Anatomy ontology ASA= Anatomical Structural Abstraction ATA= Anatomical Transformation Abstraction Mk= Metaknowledge (principles, rules, axioms) Foundational Model of Anatomy Fm = (Ao, ASA, ATA, Mk)

38. ASA = (Do, Bn, Pn, SAn) (2) where: Do= Dimensional ontology Bn= Boundary network Pn= Part-of network SAn= Spatial Association network where: Do= Dimensional ontology Bn= Boundary network Pn= Part-of network SAn= Spatial Association network Fm = (Ao, ASA, ATA, Mk) (1) Anatomical Structural Abstraction Foundational Model of Anatomy

39. ASA = (Do, Bn, Pn, SAn) (2) where: Ln = Location On = Orientation Cn = Connectivity where: Ln = Location On = Orientation Cn = Connectivity Fm = (Ao, ASA, ATA, Mk) (1) Spatial Association Network SAn = (Ln, On, Cn) (3) Foundational Model of Anatomy

40. Right Ventricle Cardiac Chamber Cardiac Chamber Organ Subdivision Organ Subdivision Organ Part Anatomical Structure Anatomy Ontology -is a-

41. Right Ventricle Cardiac Chamber Cardiac Chamber Organ Subdivision Organ Subdivision Organ Part Anatomical Structure Anatomy Ontology -is a- Polyhedron Volume (3-D) Dimensional Ontology Dimensional Ontology

42. Right Ventricle Cardiac Chamber Cardiac Chamber Organ Subdivision Organ Subdivision Organ Part Anatomical Structure Anatomy Ontology -is a- Polyhedron Volume (3-D) Spatial Ontology Sternocostal Surface Sternocostal Surface Diaphragmatic Surface Diaphragmatic Surface bounded by boundary of Anatomical Feature Anatomical Feature Surface (2-D) bounded by Right Coronary Sulcus Right Coronary Sulcus Anterior Interventricular Sulcus Anterior Interventricular Sulcus Line (1-D) bounded by Coronary Sulcus Coronary Sulcus Inferior margin of heart Inferior margin of heart Apex Boundary Network -is a- Posterior IV Sulcus Posterior IV Sulcus Crux of heart Anatomical Landmark Anatomical Landmark Point (1-D) -is a-

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

44. Right Ventricle Cardiac Chamber Cardiac Chamber Organ Subdivision Organ Subdivision Organ Part Anatomical Structure Anatomy Ontology -is a- Polyhedron Volume (3-D) Spatial Ontology Sternocostal Surface Sternocostal Surface Diaphragmatic Surface Diaphragmatic Surface bounded by boundary of Anatomical Feature Anatomical Feature Surface (2-D) bounded by Right Coronary Sulcus Right Coronary Sulcus Anterior Interventricular Sulcus Anterior Interventricular Sulcus Line (1-D) bounded by Coronary Sulcus Coronary Sulcus Inferior margin of heart Inferior margin of heart Apex Boundary Network -is a- Posterior IV Sulcus Posterior IV Sulcus Crux of heart Anatomical Landmark Anatomical Landmark Point (1-D) -is a- Part-of Network Part-of Network HeartHeart super- object super- object Inflow part of RV of RV Inflow part of RV of RV Infundibulum Wall of RV Cavity of RV subobject -is a- has Cavity of infund. infund. Cavity of infund. infund. Cavity of infl.part infl.part has adjacency adjacency anterioranteriorinferiorinferior to left Left ventricle ventricle Pericardial sac sacPericardial has adjacency adjacency DiaphragmDiaphragm inferiorinferior Spatial Association Network

45. Foundational Model of Anatomy Fm = (Ao, ASA, ATA, Mk) Fm BODY = {Fm ANATOMICAL_ENTITY }

46. Goals: Why we need to explain the brain to a computer? What to explain about the brain to a computer? How to do it? How to do it? What uses will it have? Explaining the Brain to a Computer

47. What about non-anatomical information? Is it an attribute of an anatomical structure? Does it need its own symbolic model? Adopt from existing sources? Integrate with anatomy model?

48. What to explain about the brain to a computer? "What is the knowledge we need to classify?" "What levels of knowledge are to be included?" "Explicit definition of domain of neuroscience is a daunting task." HBP PIs' question/comments

49. What to explain about the brain to a computer? Summary of strategy Constrain concept domain "Divide and conquer”; Priority: Symbolic Model of anatomical structure non-ambiguitycomprehensiveness highest level of granularity Use anatomy model as the logical foundation for other concept domains.

51. Goals: Why we need to explain the brain to a computer? What to explain about the brain to a computer? How to do it? How to do it? What uses will it have? Explaining the Brain to a Computer

52. How can the FM explain the brain to a computer? "No two anatomists agree on the precise definition of an anatomical structure” HBP PIs' question/comments Principled Modeling = Foundational Principles + Explicit Definitions

53. Foundational Principles Assertions that provide the basis for reasoning and action Constraint principle Definition principle Constitutive principle Organizational unit principle Structural relationship principle Representation principle Constraint principle Definition principle Constitutive principle Organizational unit principle Structural relationship principle Representation principle How can the FM explain the brain to a computer?

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

55. Principled Modeling Prototype problems: 1.How to reconcile different naming and classification conventions? 2. How to assure inheritance? 3.How to represent different and overlapping part-whole relationships? 4.How to represent different kinds of location attributes?

56. Principled Modeling Foundational Principles + Explicit Definitions Desiderata for definitions: Consistency with declared principles and context of modeling; State the essence of concepts in terms of their characteristics (attributes); Defining attributes should be essential characteristics shared by all members of a class; Include genus and differentiae.

57. HOW does FM reconcile different naming conventions? Semantic specificity Synonyms …………….. (e.g., esophagus) Homonyms …….……… (e.g., base of heart) Semantic expressivity ( e.g., unnamed entities …. parts of right ventricle)

58. Protégé

59. Semantic Specificity: synonyms

62. Homonym: ‘Base of heart’ Anteriorview Posteriorview Semantic Specificity: homonyms

65. Foundational Model Builder

66. Foundational Model Builder

67. Preferred name: Base of heart (anatomical)

69. Preferred name: Base of heart (clinical)

70. Semantic Specificity one preferred name for each anatomical entity associate synonyms with each preferred name disallow homonyms; use extensions one preferred name for each anatomical entity associate synonyms with each preferred name disallow homonyms; use extensions Assured in FM by:

71. Semantic Expressivity Ambiguous part-whole relationships Right ventricle

72. Semantic Expressivity Ambiguous part-whole relationships Infundibulum Right ventricle

73. Semantic Expressivity Ambiguous part-whole relationships Infundibulum Right ventricle Outflow part

74. Semantic Expressivity Ambiguous part-whole relationships Right ventricle Infundibulum Outflow part Right ventricle

75. Semantic Expressivity Ambiguous part-whole relationships Right ventricle Infundibulum Outflow part Right ventricle Inflow part

78. Preferred Name: Inflow part of right ventricle

79. UMLS

80. Leaf terms (concepts)

81. Multiple layers of meaning

83. Principled Modeling Prototype problems: 1.How to reconcile different naming and classification conventions? 2. How to assure inheritance? 3.How to represent different and overlapping part-whole relationships? 4.How to represent different kinds of location attributes?

84. HOW does FM reconcile different naming conventions? Knowledge sources Traditional hard-copy sources Textbooks, term lists Controlled Medical Terminologies (CMT)

85. Traditional knowledge sources: textbooks

86. Traditional knowledge sources: Term lists

87. Controlled Medical Terminologies MeSH (Medical Subject Headings) SNOMED (Systematized Nomenclature of Medicine) The Read Codes GALEN (General Architecture for Languages Encyclopedias and Nomenclatures in Medicine) NeuroNames (University of Washington) UMLS (Unified Medical Language Systems) US National Library of Medicine MeSH (Medical Subject Headings) SNOMED (Systematized Nomenclature of Medicine) The Read Codes GALEN (General Architecture for Languages Encyclopedias and Nomenclatures in Medicine) NeuroNames (University of Washington) UMLS (Unified Medical Language Systems) US National Library of Medicine

88. Controlled Medical Terminologies Representation of Anatomy no consistent scheme for modeling anatomy all schemes are consistent with traditional hard-copy sources contain inconsistencies Why? Context for modeling is broad; Modeling principles are not declared; Explicit definitions are not formulated.

89. Esophagus Leaf concept

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

91. Definition Esophagus is an ‘organ with an organ cavity’, which connects the pharynx to the stomach

92. DefinitionDefinition Organ with organ cavity is a ‘cavitated organ’, the morphological parts of which surround a continuous cavity, which contains one or more body substances.

93. DefinitionDefinition Cavitated organ is an ‘organ’, the morphological parts of which surround one or more cavities, which contain one or more body substances.

94. DefinitionDefinition Organ is an ‘anatomical structure’,which consists of the maximal set of organ parts so connected to one another that together they constitute a self- contained unit of macroscopic anatomy, morphologically distinct from other such units.

95. DefinitionDefinition Anatomical structure is a ‘material physical anatomical entity’ which is an object generated by the coordinated expression of groups of genes; it consists of parts that are themselves anatomical structures.

96. Principled Modeling Prototype problems: 1.How to reconcile different naming and classification conventions? 2. How to assure inheritance? 3.How to represent different and overlapping part-whole relationships? 4.How to represent different kinds of location attributes?

97. Material Physical Anatomical Entity Material Physical Anatomical Entity -is a- Anatomical Structure Anatomical Structure Non-material Physical Anatomical Entity Non-material Physical Anatomical Entity

98. Material Physical Anatomical Entity Material Physical Anatomical Entity -is a- Anatomical Structure Anatomical Structure Non-material Physical Anatomical Entity Non-material Physical Anatomical Entity Physical Anatomical Entity Physical Anatomical Entity Conceptual Anatomical Entity Conceptual Anatomical Entity

99. Material Physical Anatomical Entity Material Physical Anatomical Entity -is a- Anatomical Structure Anatomical Structure Non-material Physical Anatomical Entity Non-material Physical Anatomical Entity Physical Anatomical Entity Physical Anatomical Entity Conceptual Anatomical Entity Conceptual Anatomical Entity

100. Material Physical Anatomical Entity Material Physical Anatomical Entity -is a- Anatomical Structure Anatomical Structure Non-material Physical Anatomical Entity Non-material Physical Anatomical Entity Physical Anatomical Entity Physical Anatomical Entity Conceptual Anatomical Entity Conceptual Anatomical Entity

101. Material Physical Anatomical Entity Material Physical Anatomical Entity -is a- Anatomical Structure Anatomical Structure Non-material Physical Anatomical Entity Non-material Physical Anatomical Entity Physical Anatomical Entity Physical Anatomical Entity Conceptual Anatomical Entity Conceptual Anatomical Entity Organ Part Organ Part

102. Material Physical Anatomical Entity Material Physical Anatomical Entity -is a- Anatomical Structure Anatomical Structure Non-material Physical Anatomical Entity Non-material Physical Anatomical Entity Physical Anatomical Entity Physical Anatomical Entity Conceptual Anatomical Entity Conceptual Anatomical Entity Organ Part Organ Part Organ Part Organ Part Tissue Organ component Organ subdivision

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

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

105. OrganOrgan Solid Organ Cavitated Organ Organ with cavitated organ part Organ with cavitated organ part Organ with organ cavity Organ with organ cavity HeartHeartEsophagusEsophagus -is a- Anatomy Ontology

106. 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.

107. Assurance of inheritance

111. Test What is the brain? To which Ao class would you assign the brain?

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

113. Organ Definition:Organ is an anatomical structure is an anatomical structure consists ofmaximal sets of organ parts consists ofmaximal sets of organ parts connected to one another constitute self-contained unit distinct from other units connected to other organs connected to other organs constitutesorgan system constitutesorgan system body part

114. Organ system Definition: Organ system anatomical structure is an anatomical structure members of predominantly one organ subclass; consists ofmembers of predominantly one organ subclass; interconnected by zones of continuity; interconnected by zones of continuity; connected to other organ systems constitutesthe human body

115. Definition of neuraxis NeuroNames: central nervous systemStedman’s: "the axial, unpaired part of the central nervous system....in contrast to the paired cerebral hemispheres" Dorland’s: an axon; central nervous system.

116. What is the brain?

120. Principled Modeling Prototype problems: 1.How to reconcile different naming and classification conventions? 2. How to assure inheritance? 3.How to represent different and overlapping part-whole relationships? 4.How to represent different kinds of location attributes?

121. Attributed Part-Whole Relationships

122. Shared parts Tracheobronchial tree Lungs

123. Shared parts (Cranial Nerves: Wilson-Pauwels et al.) Oculomotor Nerve

124. Shared parts

125. Anatomical/Arbitrary Parts (Netter’s Atlas of Human Anatomy)

126. Anatomical/Arbitrary Parts Cerebral vasculature of P54

127. Anatomical/Arbitrary Parts M1 M2 M3

128. Anatomical/Arbitrary Parts

134. Granularity of parts Anterior viewPosterior view Esophagus

135. Granularity of parts

149. (Alberts et al.: Molecular Biology of the Cell) Nuclear pore complex

150. ASA = (Do, Bn, Pn, SAn) (2) where: Do= Dimensional ontology Bn= Boundary network Pn= Part-of network SAn= Spatial Association network where: Do= Dimensional ontology Bn= Boundary network Pn= Part-of network SAn= Spatial Association network Fm = (Ao, ASA, ATA, Mk) (1) Anatomical Structural Abstraction Foundational Model of Anatomy

151. What is a cerebral sulcus a part of? Test

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

153. What is a cerebral sulcus a part of?

154. Principled Modeling Prototype problems: 1.How to reconcile different naming and classification conventions? 2. How to assure inheritance? 3.How to represent different and overlapping part-whole relationships? 4.How to represent different kinds of location attributes?

155. How to represent different location relationships? "Location, location, location; surface coordinates, scanner coordinates, Talairach coordinates, etc.; not standard, not universally accepted. Multiple forms of location definition need to be supported." HBP PIs' question/comment

156. ASA = (Do, Bn, Pn, SAn) (2) where: Ln = Location On = Orientation Cn = Connectivity where: Ln = Location On = Orientation Cn = Connectivity Fm = (Ao, ASA, ATA, Mk) (1) Spatial Association Network SAn = (Ln, On, Cn) (3) How to represent different location relationships?

157. How

158. How

159. How

160. How to represent different location relationships? Adjacency Anterior viewPosterior view Esophagus

161. T2-3 T8

162. Anterior Posterior How to represent different location relationships? Coordinates How

163. How How Anterior Posterior Right lateral Right lateral Left lateral Left lateral

164. How to represent different location relationships? Adjacency How Pericardial sac Pericardial sac

165. Anterior Posterior How to represent different location relationships? Coordinates How Right lateral Right lateral Left lateral Left lateral Right AnteriorLeft Anterior Right PosteriorLeft Posterior Right Antero- lateral Right Postero- lateral Left Postero- lateral Left Antero- lateral

166. T2-3 T8

167. How to represent different location relationships? Adjacency How

168. Principled Modeling Prototype problems: 1.How to reconcile different naming and classification conventions? 2. How to assure inheritance? 3.How to represent different and overlapping part-whole relationships? 4.How to represent different kinds of location attributes?

169. Goals: Why we need to explain the brain to a computer? What to explain about the brain to a computer? How to do it? How to do it? What uses will it have? Explaining the Brain to a Computer

170. ASA = (Do, Bn, Pn, SAn) (2) Ln = (Cnmt, Adj, QCrd) (4) Fm = (Ao, ASA, ATA, Mk) (1) Principled Modeling SAn = (Ln, On, Cn) (3) How can the FM explain the brain to a computer?

171. How Challenges for modeling neuroanatomy Superimposed FMRI and cortical language maps

172. How can the FM explain the brain to a computer? Challenges for modeling neuroanatomy Independent symbolic model for brain? Integrate with nervous system; Neuroanatomy model? Concept of Foundational Model valid for brain? Integrate with Foundational Model of whole body? Reuse available terminologies NeuroNames?

173. How can the FM explain the brain to a computer? Challenges for modeling neuroanatomy How to represent Individual variations in brain anatomy Classes of variants Anatomy of individuals Multiple species Selected species Vertebrate anatomy FM

174. Goals: Why we need to explain the brain to a computer? What to explain about the brain to a computer? How to do it? How to do it? What uses will it have? Explaining the Brain to a Computer

175. What uses will symbolic brain model have? Evaluation Validity of knowledge representations scheme consistency,comprehensiveness,expressivity How much anatomy does the computer know? How can we test it? Knowledge-based applications

176. Symbolic Information Image Repository 2-D Images 2-D Images 2-D Annotations 2-D Annotations 3-D Model 3-D Model 3-D Image Volumes 3-D Image Volumes Metadata Foundational Model Foundational Model

177. Symbolic Information Image Repository Protégé Annotator Brain Mapper Brain Mapper 2-D Images 2-D Images 2-D Annotations 2-D Annotations 3-D Model 3-D Model 3-D Image Volumes 3-D Image Volumes Metadata Foundational Model Foundational Model Authoring Programs

178. Symbolic Information Image Repository Protégé Annotator Brain Mapper Brain Mapper 2-D Images 2-D Images 2-D Annotations 2-D Annotations 3-D Model 3-D Model 3-D Image Volumes 3-D Image Volumes Metadata Foundational Model Foundational Model Authoring Programs Internet

179. Symbolic Information Image Repository Protégé Annotator Brain Mapper Brain Mapper 2-D Images 2-D Images 2-D Annotations 2-D Annotations 3-D Model 3-D Model 3-D Image Volumes 3-D Image Volumes Metadata Foundational Model Foundational Model Knowledge Server Knowledge Server Image Server Image Server Data Server Data Server Graphics Server Graphics Server Authoring Programs Internet

180. Symbolic Information Image Repository Protégé Annotator Brain Mapper Brain Mapper DA Atlases DA Atlases Tutor Consultant 2-D Images 2-D Images 2-D Annotations 2-D Annotations 3-D Model 3-D Model 3-D Image Volumes 3-D Image Volumes Metadata Foundational Model Foundational Model Knowledge Server Knowledge Server Image Server Image Server Data Server Data Server Graphics Server Graphics Server End User Interfaces Authoring Programs Internet

181. Symbolic Information Image Repository Protégé Annotator Brain Mapper Brain Mapper DA Atlases DA Atlases Tutor Consultant 2-D Images 2-D Images 2-D Annotations 2-D Annotations 3-D Model 3-D Model 3-D Image Volumes 3-D Image Volumes Metadata Foundational Model Foundational Model Metaknowledge Knowledge Server Knowledge Server Image Server Image Server Data Server Data Server Graphics Server Graphics Server DIGITAL ANATOMIST End User Interfaces Authoring Programs Internet

182. End User Interfaces DIGITAL ANATOMIST Knowledge Server Knowledge Server Image Server Image Server Data Server Data Server Graphics Server Graphics Server Symbolic KB Image Repository Anatomy Education Anatomy Education Brain Map Visualizer Brain Map Visualizer Radiation Oncology Radiation Oncology 2-D Images 2-D Images 2-D Annotations 2-D Annotations 3-D Model 3-D Model 3-D Image Volumes 3-D Image Volumes Clinical Info Foundational Model Foundational Model Metaknowledge Authoring Programs Clinical Applications

183. Conclusions What is a …. ? OntologyTaxonomy Symbolic Model Knowledge Base

184. Conclusions What is an ontology ? a theory about the nature of the kinds of things that exist; an academic pursuit that studies such theories; a conceptualization of a domain; a document or file that formally defines relationships among terms; an explicit formal specification of terms and the relations among them; a taxonomy plus a set of inference rules.

185. Conclusions What is Ao of FM ? taxonomic classification based on explicit definition of concepts, inheritance of definitional structural attributes; consistent with foundational principles. What is a taxonomy ? a document or file that defines classes of objects and relations among them.

186. Conclusions What is a symbolic model ? a conceptualization of a domain of discourse represented with non-graphical symbols; in computer-processible (“understandable”) form; support inference (reasoning).

187. Conclusions What is a foundational model ? is a symbolic model; declares the principles for including concepts and relationships that are implicitly assumed when knowledge of the domain is applied in different contexts; explicitly defines concepts and relationships necessary and sufficient for consistently modeling the structure of the coherent knowledge domain.

188. Conclusions What is a knowledge base ? an ontology together with sets of instances of its classes; an integration of several symbolic models that conceptualize the domains pertinent to a set of problems.

189. Conclusions Expectations Expectations (Neuroanatomy Ontology Workshop Summary) "Index and retrieve neuroscience information by species for mouse, rat, macaque, human; Define several hierarchical schemes for grouping primary structures to support accessing information in bigger chunks; Specify the relation of several thousand synonyms to allow the retrieval of information in terms of different nomenclatures; Provide atlases of segmented coronal brain sections for warping of MRI and PET scans."

190. Conclusions Traditional knowledge sources do not meet the needs of knowledge modeling in the information age; Need next-generation knowledge sources Neuro-anatomy FM Neuro-anatomy FM should be a resource for the development of knowledge-based applications Neuro-anatomy FM should be a resource for the development of knowledge-based applications

191. Conclusions Importance of and opportunity for modeling deep knowledge in a constrained domain; Collaboration between Domain experts basic and clinical neuroscientists Knowledge modelers; The future of biomedical concept representation prerequisite for knowledge-based applications enhancement of CMTs HBP's trend-setting initiative

194. Foundational Principles Constraint Principle The abstraction should model physical organization of the human body physical organization of the human body from an anatomical viewpoint from an anatomical viewpoint Physical anatomical entities generated by coordinated gene expression generated by coordinated gene expression

195. Foundational Principles Constitutive Principle: Anatomical Structures Anatomical Structures constituted by anatomical structures largest: organism smallest: macromolecule Anatomical Spatial Entities constituted by anatomical spatial entities of same dimension

196. Foundational Principles Organizational Unit Principle: Organ is the unit of macroscopic anatomy; Organ is the unit of macroscopic anatomy; Subclasses of Anatomical Structure Subclasses of Anatomical Structure constitute organs constitute organs constituted by organs constituted by organs