Semantic Network (SN) and Biomedical Ontology

1
Semantic Network (SN) and Biomedical Ontology

• Barry Smith
• Department of Philosophy, University at Buffalo
• Institute for Formal Ontology and Medical
  Information Science
• ifomis.org

2
Assumption

• SN is designed to support automatic reasoning
  involving multiple UMLS source terminologies
• Conclusion
• Relations in SN are very important

3
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

4
Part_of as a relation between classes is more
problematic than is standardly supposed

• testis part_of human being ?
• heart part_of human being ?

5
Dr Humphreys SN lists possible significant
relations
6
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

8
Some non-is_a relations are exceptionless in this
sense

• Fully formed anatomical structure contains body
  substance

9

• But most are not
• Bacterium causes Experimental Model of Disease
• Experimental Model of Disease affects Fungus
• Experimental model of disease is_a Pathologic
  Function

10

• 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 peoples heads
• the problem is precisely that different user
  communities use different concepts

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Promise of evidence-based medicine in the
genomics eraintegrating 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 SNs
• 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

• ltclass, classgt is_a, part_of, ...
• ltinstance, classgt this explosion instance_of the
  class explosion
• ltinstance, instancegt Marys heart part_of Mary

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Kinds of relations

• ltclass, classgt is_a, part_of, ...
• ltinstance, classgt this explosion instance_of the
  class explosion
• ltinstance, instancegt Marys heart part_of Mary
• instance-level part_of is a primitive (you
  cant 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

22
transformation_of
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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embryological development
27
tumor development
C1
C c at t
c at t1
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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 b
• where 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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prevents

• Definition 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

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http//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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UMLS Semantic Types
Entity
Event
Physical Object
Conceptual Entity
Phenomenon or Process
Activity
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(No Transcript)
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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 doesnt 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_with
• disrupts Alters or influences an already
  existing condition, state, or situation. Produces
  a negative effect on. Inverse disrupted_by
• prevents Stops, hinders or eliminates an
  action or condition. Inverse prevented_by
• complicates Causes to become more severe or
  complex or results in adverse effects. Inverse
  complicated_by
• manages Administers, or contributes to the
  care of an individual or group of individuals.
  Inverse managed_by
• treats Applies a remedy with the object of
  effecting a cure or managing a condition.
  Inverse treated_by
• affects 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_by
• performs 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_property
• conceptual_part_of Conceptually a portion,
  division, or component of some larger whole.
  Inverse has_conceptual_part
• evaluation_of Judgment of the value or degree
  of some attribute or process. Inverse
  has_evaluation
• measures Ascertains or marks the dimensions,
  quantity, degree, or capacity of. Inverse
  measured_by
• diagnoses Distinguishes or identifies the
  nature or characteristics of. Inverse
  diagnosed_by
• issue_in Is an issue in or a point of
  discussion, study, debate, or dispute. Inverse
  has_issue
• derivative_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_location
• 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
• surrounds Establishes the boundaries for, or
  defines the limits of another physical structure.
  This includes limits, bounds, confines, encloses,
  and circumscribes. Inverse surrounded_by
• traverses Crosses or extends across another
  physical structure or area. This includes crosses
  over and crosses through. Inverse traversed_by
• spatially_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
• Discussion
• The 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 SNs 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
• Conclusion
• A number of proposals have been advanced to
  increase SNs 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 SNs 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.