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Semantic Network (SN) and Biomedical Ontology

Barry SmithDepartment of Philosophy, University at Buffalo

Institute for Formal Ontology and Medical Information Science

ifomis.org

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AssumptionSN is designed to support automatic reasoning involving multiple UMLS source terminologies

Conclusion:Relations in SN are very important

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Inheritance

Body part, Organ or Organ Component location_of Biologic Function

Therefore

Body Part, Organ or Organ Component location_of Disease or Syndrome

Alexa: “We can sometimes infer ... you have to bring some medical knowledge to bear”

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Part_of as a relation between classes is more problematic than is

standardly supposed

testis part_of human being ?

heart part_of human being ?

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Dr Humphreys: SN lists “possible significant relations”

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What we need for automatic inference is uniformly (necessarily)

significant relations

A is_a B

Every instance of A is an instance of B

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What we need for automatic inference is uniformly (necessarily)

significant relations

A is_a B

Every instance of A is an instance of B

We hope all is_a relations are exceptionless in this sense

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Some non-is_a relations are exceptionless in this sense

Fully formed anatomical structure contains body substance

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But most are not

Bacterium causes Experimental Model of Disease

Experimental Model of Disease affects Fungus

Experimental model of disease is_a Pathologic Function

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Bacterium causes Experimental Model of Disease

causes – Brings about a condition or an effect. Implied here is that an agent, such as for example, a pharmacologic substance or an organism, has brought about the effect. This includes induces, effects, evokes, and etiology.

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GALEN: Vomitus contains carrot

Gene Ontology: Menopause part_of Death

HL7: Individual Allele is_a Act of Observation

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Thesis: Biomedical ontology integration

will never be achieved through integration of meanings or concepts in people’s heads

the problem is precisely that different user communities use different concepts

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Promise of evidence-based medicine in the genomics era:

integrating biomedical terminologies with EHR data

need facility for dealing with time and instances (particulars, actual cases)

with this tumor here and now in this breast ...

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Move from associative relations between meanings to strictly

defined relations between the entities themselves

See: Smith, Ceusters, Klagges, Köhler, Kumar, Lomax, Mungall, Neuhaus, Rector, Rosse

“Relations in Biomedical Ontologies”Genome Biology, in press

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Clear instructions

Fewer mistakes

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Key idea

To define ontological relations like SN’s

part_of, contains, adjacent-to

we need also to take account of instances and time

(= link to Electronic Health Record)

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Kinds of relations

<class, class>: is_a, part_of, ...

<instance, class>: this explosion instance_of the class explosion

<instance, instance>: Mary’s heart part_of Mary

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Kinds of relations

<class, class>: is_a, part_of, ...

<instance, class>: this explosion instance_of the class explosion

<instance, instance>: Mary’s heart part_of Mary = instance-level part_of is a primitive (you can’t define everything, on pain of circularity)

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part_of

A part_of B =def.

for all a and all t,

if a is an instance of A at time t,

then there is some instance b of B

such that a is an instance-level part_of b at t

ALL-SOME STRUCTURE

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part_of

A part_of B =def.

for all a and all t,

if a is an instance of A at time t,

then there is some instance b of B

such that a is an instance-level part_of b at t

ALL-SOME STRUCTURE

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testis part_of human being - NO

human testis part_of human being - YES

human ovary part_of human being - YES

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transformation_of

c at t1

C

c at t

C1

time

same instance

mature RNA transformation_of pre-RNA

fetus transformation_of embryo

adult transformation_of child

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transformation_of

C2 transformation_of C1 =def. any instance

of C2 was at some earlier time an instance

of C1

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Note the problem of inverses here

Not every child becomes transformed into an adult

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The Granularity Gulf as an obstacle to reasoning

most existing data-sources are of fixed, single granularity

many (all?) clinical phenomena cross granularities

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C

c at t c at t1

C1

embryological development

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C

c at t c at t1

C1

tumor development

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Advantages of the methodology of enforcing commonly accepted

coherent definitions

promote quality assurance (better coding)

guarantee automatic reasoning across ontologies and across data at different granularities, from molecule to clinic

yields direct connection to times and instances in EHR

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Automatic reasoning

non-is_a relations are all-some relations A R B =def for all instances a of A there is some instance b

of B such that a r bwhere r is some instance-level relation

If you know A R B, and you know that a is an instance of A, then you know that there is some instance b of B

and inheritance is unrestrained (exceptionless)if you know B R C you can reason with this instance b to

infer that there is some C, and so on

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Conclusions for SN

Remove the merely ‘possibly significant relations’ (these are less than facts)

Reform definitions (remove circularity)

Remove those relations, such as prevents which cannot be given a coherent instance-based all-some definition

Reform treatment of inverses

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preventsDefinition: Stops, hinders or eliminates an

action or condition.Inverse: prevented_by

contraception prevents pregnancy

pregnancy prevented_by contraception

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Better treatment of prevention

contraception

causes

prevention_of_pregnancy

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Reform treatment of inverses

adjacent_to – “Close to, near or abutting another physical unit with no other structure of the same kind intervening. This includes adjoins, abuts, is contiguous to, is juxtaposed, and is close to.”

Inverse: adjacent_to

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Adjacent_to is not its own inverse

nuclear membrane adjacent_to cytoplasm

BUT NOT:

cytoplasm adjacent_to nuclear membrane

ovary adjacent_to parietal pelvic peritoneum

BUT NOT:

parietal pelvic peritoneum adjacent_to ovary

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Better treatment of inverses

Use preceded_by not precedes as primary relation

preceded_by supports inheritance (supports automatic reasoning)

embryological development precedes birth NOT EXCEPTIONLESS

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If NLM does not reform SN

in something like this way, then someone else will build a competitor to integrate the UMLS for purposes of automatic reasoning and integration across granularities

37http://ifomis.org

The End

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Human-Caused Phenomenon or Process (Environmental Effect of Humans):

Phenomenon and Process put together

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Entity Event

ActivityPhenomenon or

Process

Physical Object

Conceptual Entity

UMLS Semantic Types

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gene part_of cell component

body system conceptual_part_of

fully formed anatomical structure

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conceptual entity

idea or concept

functional concept

body system

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But:

Gene or Genome is defined as: “A specific sequence … of nucleotides along a molecule of DNA or RNA …”

and

nucleotide sequence is_a conceptual entity

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entity

physical conceptual object entity

idea or concept

functional concept

body system

confusion of entity and concept

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Functional Concept:

Body system is_a Functional Concept.

but:

Concepts do not perform functions or have physical parts.

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This:

is not a concept

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UMLS-SN Semantic Relation

producesDefinition: Brings forth, generates or creates. Inverse: produced_by

artificial insemination produces pregnancy

pregnancy produced by artificial insemination

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Definitions

conceptual_part_of – Conceptually a portion, division, or component of some larger whole.

should not be circular

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part_of – “Composes, with one or more other physical units, some larger whole. This includes component of, division of, portion of, fragment of, section of, and layer of.” Inverse: has-part

contains – “Holds or is the receptacle for fluids or other substances. This includes is filled with, holds, and is occupied by.” Inverse: contained_in

consists_of – “Is structurally made up of in whole or in part of some material or matter. This includes composed of, made of, and formed of.” Inverse: constitutes

connected_to – “Directly attached to another physical unit as tendons are connected to muscles. This includes attached to and anchored to.” Inverse: connected_to

interconnects – “Serves to link or join together two or more other physical units. This includes joins, links, conjoins, articulates, separates, and bridges.” Inverse: interconnected by

branch_of – “Arises from the division of. For example, the arborization of arteries.” Inverse: has_branch

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tributary_of – “Merges with. For example, the confluence of veins.” Inverse: has_tributary

ingrediant_of – “Is a component of, as in a constituent of a preparation.” Inverse: has_ingredient

physically_related_to – “Related by virtue of some physical attribute or characteristic.” Inverse: physically_related_to

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connected_to and connects not clearly defined

ingrediant_of doesn’t fit

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temporally_related_to – (co-occurs_with; precedes): The relevant definitions are as follows:

precedes – “Occurs earlier in time. This includes antedates, comes before, is in advance of, predates, and is prior to.” Inverse: follows

co-occurs_with – “Occurs at the same time as, together with, or jointly. This includes is co-incident with, is concurrent with, is contemporaneous with, accompanies, coexists with, and is concomitant with.” Inverse: co-occurs_with

temporally_related_to – “Related in time by preceding, co-occuring with, or following.” Inverse: temporally_related_to

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Too unspecific. KIF annotations?

affects – (interacts_with; disrupts; prevents; complicates; manages; treats): The relevant definitions are as follows:

interacts_with – “Acts, functions, or operates together with.” Inverse: interacts_withdisrupts – “Alters or influences an already existing condition, state, or situation. Produces a

negative effect on.” Inverse: disrupted_byprevents – “Stops, hinders or eliminates an action or condition.” Inverse: prevented_bycomplicates – “Causes to become more severe or complex or results in adverse effects.”

Inverse: complicated_bymanages – “Administers, or contributes to the care of an individual or group of individuals.”

Inverse: managed_bytreats – “Applies a remedy with the object of effecting a cure or managing a condition.”

Inverse: treated_byaffects – “Produces a direct effect on. Implied here is the altering or influencing of an existing

condition, state, situation, or entity. This includes has a role in, alters, influences, predisposes, catalyzes, stimulates, regulates, depresses, impedes, enhances, contributes to, leads to, and modifies.” Inverse: affected_by

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interacts_with need not be affects

occurs_in – (process_of): The relevant definitions are as follows:

process_of – “Action, function, or state of.” Inverse: has_process

occurs_in – “Takes place in or happens under given conditions, circumstances, or time periods, or in a given location or population. This includes appears in, transpires, comes about, is present in, and exists in.” Inverse: has_occurrence

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No reason why one is a subclass of the other

brings_about – (produces, causes): The relevant definitions are as follows:

produces – “Brings forth, generates or creates. This includes yields, secretes, emits, biosynthesizes, generates, releases, discharges, and creates.” Inverse: produced_by

causes – “Brings about a condition or an effect. Implied here is that an agent, such as for example, a pharmacologic substance or an organism, has brought about the effect. This includes induces, effects, evokes, and etiology.” Inverse: caused_by

brings_about – “Acts on or influences an entity.” Inverse: brought_about_by

performs – (carries_out, practices, exhibits): The relevant definitions are as follows:

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carries_out – “Executes a function or performs a procedure or activity. This includes transacts, operates on, handles, and executes.” Inverse: carried_out_by

practices – “Performs habitually or customarily.” Inverse: practiced_by

exhibits – “Shows or demonstrates.” Inverse: exhibited_byperforms – “Executes, accomplishes, or achieves an

activity.” Inverse: performed_by

Difference between “performs” and “carries out” unclear

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functionally_related_to – (manifestation_of; affects; occurs_in; uses; indicates; result_of; brings_about; performs): The relevant definitions are as follows:

manifestation_of – “That part of a phenomenon which is directly observable or concretely or visibly expressed, or which gives evidence to the underlying process. This includes expression of, display of, and exhibition of.” Inverse: has_manifestation

uses – “Employs in the carrying out of some activity. This includes applies, utilizes, employs, and avails.” Inverse: used_by

indicates – “Gives evidence for the presence at some time of an entity or process.” Inverse: indicated_by

result_of – “The condition, product, or state occurring as a consequence, effect, or conclusion of an activity or process. This includes product of, effect of, sequel of, outcome of, culmination of, and completion of.” Inverse: has_result

functionally_related_to – “Related by the carrying out of some function or activity. ” Inverse: functionally_related_to

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analyzes – (assesses_effect_of): The relevant definitions are as follows:

assesses_effect_of – “Analyzes the influence or consequences of the function or action of.” Inverse: assessed_for_effect_by

analyzes – “Studies or examines using established quantitative or qualitative methods. ” Inverse: analyzed_by

conceptually_related_to – (property_of; conceptual_part_of; evaluation_of; measures; diagnoses; issue_in; derivative_of; developmental_form_of; degree_of; measurement_of; method_of; analyzes): The relevant definitions are as follows:

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property_of – “Characteristic of, or quality of.” Inverse: has_propertyconceptual_part_of – “Conceptually a portion, division, or component of some larger whole.” Inverse:

has_conceptual_partevaluation_of – “Judgment of the value or degree of some attribute or process.” Inverse:

has_evaluationmeasures – “Ascertains or marks the dimensions, quantity, degree, or capacity of.” Inverse:

measured_bydiagnoses – “Distinguishes or identifies the nature or characteristics of.” Inverse: diagnosed_byissue_in – “Is an issue in or a point of discussion, study, debate, or dispute.” Inverse: has_issuederivative_of – “In chemistry, a substance structurally related to another or that can be made from the

other substance. This is used only for structural relationships. This does not include functional relationships such as metabolite of, by product of, nor analog of.” Inverse: has_derivative

developmental_form_of – “An earlier stage in the individual maturation of.” Inverse: has_developmental_form

degree_of – “The relative intensity of a process or the relative intensity or amount of a quality or attribute.” Inverse: has_degree

measurement_of – “The dimension, quantity, or capacity determined by measuring.” Inverse: has_measurement

method_of – “The manner and sequence of events in performing an act or procedure.” Inverse: has_method

conceptually_related_to – “Related by some abstract concept, thought, or idea.” Inverse: conceptually_related_to

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spatially_related_to – (location_of; adjacent_to; surrounds; traverses): The relevant definitions are as follows:location_of – “The position, site, or region of an entity or the site of a process.” Inverse: has_locationadjacent_to – “Close to, near or abutting another physical unit with no other structure of the same kind intervening. This includes adjoins, abuts,

is contiguous to, is juxtaposed, and is close to.” Inverse: adjacent_tosurrounds – “Establishes the boundaries for, or defines the limits of another physical structure. This includes limits, bounds,

confines, encloses, and circumscribes.” Inverse: surrounded_bytraverses – “Crosses or extends across another physical structure or area. This includes crosses over and crosses through.”

Inverse: traversed_byspatially_related_to – “Related by place or region.” Inverse: spatially_related_to

associated_with – (physically_related_to, temporally_related_to, functionally_related_to, conceptually_related_to, spatially_related_to): associated_with is defined as “has a significant or salient relationship to.” Inverse: associated_with

DiscussionThe inclusion of the opposition Chemical Viewed Structurally and Chemical Viewed Functionally raises the suggestion that SN might be better

interpreted as clas‑sifying not entities but rather the concepts we have of such entities. The concepts we use when referring to chemicals can after all be divided quite naturally un‑der these two headings. Then, however, the root nodes of SN should be not: Entity and Event, but rather: Entity Concept and Event Concept, and the latter should themselves be re-assigned to the position of daughters of a new root Concept. A restructuring along these lines would how‑ever in other ways conflict radically with SN’s current architecture. Above all, it would con‑tradict the fact that Idea or Concept is already itself a subnode of Conceptual Entity. It would also contradict explicit statements to the effect that SN is ‘an upper-level ontology … in which all concepts are given a consistent and semantically coherent representation’. [7]

ConclusionA number of proposals have been advanced to increase SN’s effectiveness as a terminology integration platform that can support enhanced

reasoning and information retrieval. Thus [8] argues that UMLS lacks the requisite granularity, semantic types and relationships for comprehensively and consistently representing anatomical concepts in machine readable form. [9] and [10] propose enhancing the efficiency of UMLS-based reasoning systems via a clustering of SN nodes to yield more coarse-grained partitions of the network.

Our proposal is that SN’s power to support terminology-based reasoning can be enhanced through a reclassification along the lines sketched in the above. As an example of how such a reclassification would support inferences currently blocked, consider the way in which SN currently views tissues and cells as physical parts of organs, but views these organs themselves as mere conceptual parts of body systems, which are in turn conceptual parts of fully-formed anatomical structures, which are in turn physical parts of organisms. When we reclassify Body System as a Physical Entity, there is no longer a need for the distinction between conceptual and physical part-of relations. Reasoning systems can thus exploit the full power of mereology, including the rules governing transitivity of part-of.