A reference ontology for biomedical informatics: the Foundatio nal Model of Anatomy

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A reference ontology for

biomedical informatics: the Foundatio nal Model of Anatomy

Cornelius Rosse, , José L.V. Mejino Jr.

J Biomed Inform. 2003 Dec;36(6):478-500.

R00945016 任立容 R00945025 何泓毅 R00945023 許自程 R00945001 陳禹恆 R00922085 張翔竣 R00945004 陳郁文 R00945007 潘建豪 R00945013 許逸堯

2012/6/11

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Introduction

Part 1 . 任立容 R00 945016

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Background

New biomedical ontologies appear without well rela ting to traditional biology vocabulary database

Gene Ontology

Built up for collecting, combining new biology inform ation together with basic biomedical information and make a systematic coordination

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Background

New biology field

Molecular biology, Genetic biology, Bioinformatics, Sy stems biology ...,etc.

Classical biomedical field

Anatomy, Pathology, Physiology...,etc.

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Introduction – Gene Ontology

• In Unified Medical Language System (UMLS)

– Provide gene product annotation data – Set of three structured vocabularies

• Cellular component, Molecular function, Biological process

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Gene Ontology Vocabularies

Cytochrome c

molecular function : oxidoreductase activity

biological process : oxidative phosphorylation , cellular respiration cellular component terms :mitochondrial matrix

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The Foundational Model of Anatomy(FMA)

• An ontology based on Anatomy

• Use anatomy for classification of all biology terms

• Try to construct the relations of existing ontologies Foundational means anatomy is fundamental to all bio medical domains

(8)

Organization of FMA

3 Components

• Anatomy Taxonomy

• Structural concept

• Developmental biology Typographies

Courier New font : name of concept -italics- font : relationship

Bold: abbreviations

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Purpose of FMA

Not an end-user application as other ontologies

But a reusable and generalizable resource of deep anat omical knowledge and other biology knowledge

(10)

Currently

70,000 anatomical concepts

ranging in size from macromolecules and cell compone nts to major body parts

More than 110,000 terms

Related to other by more than 1.5 million instantiations of over 170 kinds of relationships

By Disciplined modeling

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Disciplined modeling

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Foundational model

• a symbolic model

• non-graphical symbols

• a conceptualization of a domain

• including concepts and relationships

• serve as a reference in terms of which other vi ews (contexts) of the domain can be correlate d.

(13)

Foundational model anatomy

• Foundational model of the physical organizatio n of the human body

• anatomy (structure)—and its coherent knowle dge domain is anatomy (science).

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Disciplined modeling

• a set of declared foundational principles

• a high level scheme for representing the refer ents of concepts and relationships in the anat omy domain

• Aristotelian definitions

• a knowledge modeling environment

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FOUNDATIONAL PRINCIPLES

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1. Unified context principle.

• strictly structural context

• serve as a reference ontology for correlating o ther (e.g.,functional, clinical) contexts

(17)

2. Abstraction level principle

• Should model canonical anatomy [ anatomy (s tructure) ]

• provide a framework for anatomical variants

• exclude instantiated anatomy [ anatomy (scien ce) ]

(18)

3. Species specificity principle.

• The initial iteration of the abstraction should model the anatomy of Homo sapiens

• but at the same time it should serve as a fram ework for the anatomy of other species.

(19)

4. Definition principle.

• Aristotelian definitions

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5. Dominant concept principle.

• An ontology’s dominant class = the class in ref erence to which other classes in the ontology are defined.

• Anatomical structure (defined in Section 3.2) s hall be the dominant class in the FMA (see Sec tion 3.2.2.2).

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6. Organizational unit principle.

• The abstraction shall have two units in terms o f which subclasses of Anatomical structure are defined: Cell and Organ.

• Other subclasses of Anatomical structure shall constitute cells or organs, or be constituted by cells or organs.

(22)

7. Content constraint principle.

• The largest anatomical structure represented s hall be the whole organism

• the smallest Biological macromolecule.

• molecules not synthesized through the expres sion of the organisms own genes shall be repr esented in separate ontologies.

(23)

8. Relationship constraint principle.

• Abstraction shall model three types of relation ships

– class subsumption relationships – static physical relationships

– transformation of anatomical entities during the o ntogeny of an organism

(24)

9. Coherence principle.

• The abstraction shall have one root, Anatomic al entity, which subsumes all entities relating t o the structural organization of the body;

(25)

10. Representation principle.

• modeled as an ontology of anatomical concep ts

• accommodate all naming conventions associat ed with these concepts.

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High level scheme

• Anatomy Taxonomy

• Anatomical Structural Abstraction

• Anatomical Transformation Abstraction

• Metaknowledge

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High level scheme

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Disciplined modeling

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3.1.3 Aristotelian definitions

• the purpose of definitions is to align all concep ts in the ontology’s domain in a coherent inher itance type hierarchy or taxonomy

• the essence of an entity is constituted by two sets of defining attributes:

the genus & the differentiae

(30)

3.1.4 Knowledge modeling enviroment

• Protégé-2000 ontology editing and knowledge acquisition environment

• frame-based architecture

• compatible with the Open Knowledge Base Co nnectivity (OKBC) protocol

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3.1.4.1 Frames, slots, slot values, and facets

• Anatomical concepts are represented as frame s, a data structure that contains all the inform ation including the properties of the entity to which that concept refers and also the relation ships of that entity to other entities

(32)

• Attributes (properties) and relationships of the entity associated with the concept are express ed as slots of the frame

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3.1.4.2 Classes and instances

• A class in the AT is a collection of anatomical e ntities or collections of collections

• Instance is the technical solution for enabling t he selective inheritance of attributes

• all concepts in the AT are subclasses of a super class and also an instance of a metaclass

(34)

3.1.4.3 Selective inheritance of attributes

• It is necessary to distinguish between the attribute s that should and should not be propagated

• 每筆資料不一定所有內容都需要被傳到下一級,因此 都有兩種屬性 class 與 instance 。前者的資訊會被傳遞 到下一級,而上一級的 template slot 被傳遞到下一級 後,被該級的 instance 當作 own slot ,定義出該級的 sl ot 與限制條件,比較像是每一級的規格定義檔,而 ow n slot 顧名思義,是自己的所以不會被傳播到下一級。

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Disciplined modeling

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Attributed relationships

• FMA is particularly rich in relationships.

• It is not sufficient to state:

• Ex:

the esophagus( 食道 ) is

continuous with the pharynx( 咽 ) and stomach( 胃 ).

(37)

Attributed relationships

• Knowledge-modeling environment is a challen ge.

• The solution is a to attach to a slot.

• Ex: A-continuous with-B

• C-adjacency-D

(38)

Anatomy taxonomy

• The taxonomy in educational, research and cli nical context is a leaf structure.

educationa l

clinical research

(39)

Root of the AT

• A more restricted concept than entity will not su bsume these concepts.

• -has part- slot , and its inverse, -part of-, are introd uced at the root of the AT.

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Principal classes

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High level classes

• volumes, surfaces, lines or points spatial dimension:

(42)

High level classes

• Anatomical space, Anatomical surface,

• Anatomical line, and Anatomical point

Mass

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Metaclass and dominant concept

• Divide by inherent 3D shape.

• Exclude foreign and abnormal structures.

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Disciplined modeling

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Units of structural organization

• Cell and Organ: organizational units of the FM A

• These are two of the subclasses of Anatomical structure

• All but two of the other subclasses of Anatomi cal structure are conceptually deriver from cell or organ

(46)

Exceptions

• Acellular anatomical structure

• Biological macromolecule

• Include these macromolecules in the FMA

(47)

Cell

• A microscopic structure

• Is an anatomical structure

• Consists of cytoplasm surrounded by a plasma membrane

• May find up 10 different implied classifications of cells in the literature

• Most consistent scheme: proposed by Lovtrup

(48)

Organ

• Is an anatomical structure

• Consists of the maximal set of organ parts

• Not only liver or thymus but hand or knee

(49)

Organ part

• Is an anatomical structure

• Consists of two or more types of tissues

• Spatially related to one another

• In patterns determined by coordinated gene e xpression

(50)

Tissue

• Is an anatomical structure

• Consists of similarly specialized cells and interc ellular matrix

(51)

Function system

• Organ system

– Constituted by organs – Musculoskeletal system

• Skeletal system

• Articular system

(52)

Anatomical cluster

• Do not fit any of Anatomical structure subclass es we describe so far

• Do not constitute the whole or a subdivision o f organ system

• Like lung and the renal pedicle

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Anatomical set

• Which represent a collection of anatomical str ucture that are members of one class

• Indirect connections exist between the memb ers

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Anatomical junction

• Subsume such anatomical structures as suture

• The commissure of the mitral valve

• Gastroesophageal junction

• Anastomosis

• Nerve plexus

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Disciplined modeling

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3.2.3 Derivation of terms

• Make anatomical information available in com putable form.

• Generalizes to all application domains of anato my.

Include in the FMA all terms that currently designate anatomical entities

Include in the FMA all terms that currently designate anatomical entities

(57)

Source of terms

• Honored English language scholarly textbooks of anatomy.

• Original journal articles from the anatomy and clinical literature.

(58)
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Naming convention

• Singular form

• Conjunctions and homonyms are not allowed

• Anatomical sets (Set of spinal nerves)

• Muscle (tissue) and Muscle(organ)

• Macroscopic parts of the body that have not p reviously been named (Upper uterine segmen t)

• “Left fifth intercostal space”

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3.3 Anatomical Structural Abstraction

• ASA is an aggregate of the structural

relationships that exist between the entities.

(61)

ASA are sets of interacting networks

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Example

• The surface of the heart forms the boundary o f the heart in the boundary network (Bn) (not Pn)

• the diaphragmatic surface of the heart is a par t of the surface of the heart (Pn)

- also part of the boundary of the heart (Pn) - also boundary of right ventricle (Bn)

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Disciplined modeling

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Anatomical Transformation Abstraction

• Definition

– Anatomical Transformation Abstraction describes the time-dependent morphological transformations of the concepts represented in the tax onomy during the human life cycle, which includes prenatal developm ent, postnatal growth and aging

• ATA scheme

– Scheme for prenatal development, not for the morphological transfor mations associated with the processes of growth and aging

– Associated with an anatomical entity in order to comprehensively conc eptualize and symbolically represent its development starting from the fertilized egg.

(65)

ATA Scheme

(66)

Phenotypic transformation

• Phenotypic transformation(PTr)

– developmental states of one individual

– Precursor, successor, a change in phenotype

For example:

Mesodermal primordium of humerus >

Cartilaginous primordium of humerus >

Ossifying humerus with primary ossification center > Ossifying humerus with secondary ossification center > Fully formed humerus

(67)

Developmental Lineage

• Developmental lineage (DL)

– an ancestor replicates itself and gives rise to two or more d escendants, each of which is phenotypically distinct from it s immediate ancestor

– ancestor, descendant, change in phenotype

(68)

Regulatory networks

• Transforming agent (TAg)

– Gene product, effect the expression of a new phenotype(Δ PT)

– ΔPT depends on the activity of Gf (facilitated ) or Gr (repres sed) within its source(Sc)

– TAg must be propagated (Prop) from the source to the targ et, which may occur within cells

(69)

Accessing FMA

(70)

Evaluating and current usage

• Low level

– Internal consistency – Comprehensiveness

• High Level

– Evaluated for its generalizability and usefulness to other projects in knowledge representation and a pplication development

(71)

Evaluating and current usage

• Comprehensiveness seems a relatively trivial problem compar ed to evaluating the FMA’s overall semantic structure and the extensive modeling of relationships.

– Difficulties: mapping of large symbolic models to one another, taking i nto account their structure as well as their terms

• GALEN’s common reference model

– there are surprisingly few homologies

• Conclusion

– the FMA has a strictly structural orientation

– We hope that the development of knowledge-based – applications calling for anatomical knowledge will be

– stimulated by access to the comprehensive FMA, pro-viding opportuni ties for its higher level evaluation

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Scaling of FMA

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6. Scaling of FMA

• FMA is to fulfill its potential as a reference ontology, it should be feasible to readily align other existing and evolving biomedi cal ontologies with it.

1. macroscopic anatomy and…

histology and the representation of cells, subcellular entities, a nd biological macromolecules

2. development of the neuroanatomical component of the FMA

Instantiation of neuroanatomical relationships is in progress

(74)

3. using the FMA as a template for the representation of the anatomy of non-human species as experimental models of human disease

The challenge is to formally represent interspecies similarities and differences at the various levels of structural organization

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7. Discussion

• FMA expresses a theory of anatomy that provides a view of th e domain consonant with the requirements of formal knowledg e and also accommodates traditional views of the domain

• The FMA’s theory of anatomy is articulated by its high level s cheme:

the semantic structure of the AT ***

the schemes of the models ASA and ATA components

(76)

7. Discussion

7.1. Salient features of the AT

• Anatomy Taxonomy

– incorporate all concepts that relate to the structure of body – including those first identified in the contemporary literatur

e and those that are newly discovered.

(77)

7. Discussion

7.1. Salient features of the AT

• specific attributes that are shared by anatomical structures ar e propagated from the root of the taxonomy to its leaves.

• semantic structure of the AT assures that all anatomical entiti es are encompassed by one attributed graph.

• The structure of the AT is a dynamic abstraction that is modi fied as a result of new insights gain into the structure of anato mical knowledge.

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7. Discussion

7.2. Relevance to bio- and biomedical informatics

1. The FMA is a domain ontology that represents deep know ledge of the structure of the human body

① large number and specificity of the structural relationships between these concepts.

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7. Discussion

7.2. Relevance to bio- and biomedical informatics

2. continuous conceptual and implementation framework

① FMA anatomical entities down to the cell level and provi de a framework for linking to the FMA ontologies and oth er data repositories.

3. adheres in its modeling to one context

① FMA is intended to meet the needs of diverse user groups

② designed as a reusable reference ontology rather than an a pplication ontology.

(80)

7. Discussion

• Such context-specific modeling results in a number of benefit s:

1. obviates duplication and redundancy in ontology developmen t, since the FMA’s contents can be reused

2. provides for consistency among independent ontologies that r ely on the FMA’s contents

3. serves as a template for the development of other ontologies

(81)

8. Conclusions

1. Anatomical knowledge represented in the FMA parallels in it s complexity and depth the knowledge.

2. FMA’s contents are processable by computers and provide fo r machine-based inference, which is a prerequisite for the dev elopment of knowledge-based applications.

3. Serving as a reference ontology for bioinformatics, the FMA may facilitate such a process.

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Thanks for your attention

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