Stuart Aitken

1

A Process Ontology for Cell Biology

• Stuart Aitken
• Artificial Intelligence Applications Institute

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Outline

• Rapid Knowledge Formation (RKF) Project
• RKF Project goals and domain
• The Cyc knowledge based-system
• RKF Tools
• Process Ontology
• General approach
• Formalisation
• Example

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Rapid Knowledge Formation

• The RKF project aims to develop tools which will
  allow domain experts to enter knowledge directly
  into the KBS.
• DARPA-funded, two teams
• CYCORP
• SRI
• Organised around Challenge Problems Cell
  Biology

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RKF

• Aim To enable biologists to construct an
  ontology/KB from a textbook source

formalise
Ontology
Alberts et al, Essential Cell Biology, 1998
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Rapid Knowledge Formation

• Key techniques
• The KBS has knowledge of the KA process
• Knowledge of salience
• Knowledge of the requirements of an adequate
  formalisation
• There is a dialogue between expert and system,
  which clarifies the concept being defined.

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Rapid Knowledge Formation

• Evaluation
• After a period of tool development,
• trials are organised, both
• expert performance, and
• KE performance is measured,
• and assessed independently.
• The evaluation is extensive over a period of 2
  weeks

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The Cyc KBS

• Cyc (Doug Lenat) is a knowledge-based system,
  under development since 1984, aiming to
  represent common sense knowledge.
• Cyc uses a large upper-level ontology
• Uses a logical language based on first-order logic

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The Cyc KBS

• Concepts in the Upper Ontology
• Thing, Agent, Event
• TangibleThing, InformationBearingObject
• . Dog, Book
• subclass(genls), instance-of(isa)
• parts, subevent, role predicates
• 1600 concepts in total in the public release
  (1998) - small of Cyc
• Classification
• Stuff-like vs Object-like
• Individual vs Set

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The Cyc KBS

• The upper-ontology supports application
  development

Thing
Upper-level
Intermediate-level
Application-level
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The Cyc KBS

• Cyc includes
• An inference engine,
• GUI,
• tools for ontology development.
• Until the RKF project, ontology development was
  by trained knowledge engineers, working with
  domain experts.

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RKF

• New tools in Cyc
• Define a new concept, and place it correctly in
  the ontology
• Refine a concept definition
• Define a new predicate
• Assert a new fact
• Define a new rule
• State an analogy
• Construct a new process

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RKF

• User interaction
• Selection of items in the interface
• Choice determined intelligently, KBS has
  knowledge of salience, and the KA process, this
  knowledge must be authored
• Browsing of the ontology
• Search
• Natural language dialogue

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Process Models
RNA Transcription
BindsTogether
Move
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Process Descriptor

• Q Name the process
• A RNA Transcription
• QSelect the type of Process that describes the
  category best
• event localised
• creation or destruction event
• say this _ _ _ _ _ _
• Q Define
• affected object _ _ _ _ _
• location _ _ _ _ _
• actor _ _ _ _ _

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Process Models

• Describing Processes
• Complex expressions at the instance level
• Simpler to describe in terms of types

subevent(Event,Event) doneBy(Event,Agent)
Upper-level
Intermediate-level
?
Application-level
ForAll ?E ?F ?G implies (subevent(?E,?G) and
isa(?E,BindsTogether) subevent(?F,?G) and
isa(?F,Move)) before(startOf(?E),startOf(?F))
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Script Vocabulary

• The Script theory defines the semantics of
  Type-Level assertions
• (typePlaysRoleInScene RNATranscription
• DNAMolecule BindsTogether
• objectActedOn)
• Requires rules for identity
• Can require complex reasoning
• Good for user input
• Can be extended to cover pre and postconditions
  of actions

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Scripts

• subevents

RNA Transcription
startsAfterStartingOfInScript
BindsTogether
Move
t
e
f
Forall subevents f of t, of type Move, and all
subevents e of t, of type BindsTogether, (startsA
fterStartingof f e) where t is of type
RNATranscription
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Scripts

• Type playing role

BindsTogether
Nucleotide
Types
Instance
N
e
objectActedOn
For some n in N, (objectActedOn e n)
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New Script Vocabulary

• Pre and Post conditions

(preconditionOfScene-negated BindsTogether
touchingDirectly ltRibonucleotide
Nucleotidegt) (postconditionOfScene
BindsTogether connectedTo ltRibonucleotide
Nucleotidegt)
BindsTogether
N
N
R
not touchingDirectly
R
connectedTo
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New Script Vocabulary
BindsTogether
Ribonucleotide
Nucleotide
Types
Set of Instances
role
role
N
R
e
Postcondition
Precondition
Some ?n in N, some ?r in R (not (touchingDirectly
?n ?r))
Some ?n in N, some ?r in R (connectedTo ?n ?r)
identity
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Script Vocabulary

• The Script vocabulary forms an intermediate
  level, which
• lies behind the Process descriptor GUI (i.e. the
  textboxes)
• Not, in itself, a taxonomy of processes, but
  allows processes to be described in detail.
• Defining the subclass relation is just one task.

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Vaccinia Virus Life Cycle

• The vaccinia virus life cycle was selected as an
  example of a complex model to formalise as a set
  of Scripts.
• The model includes actions, decomposition,
  ordering, objects-playing-roles and
  pre/postconditions
• It is a good test for the Script vocabulary

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Vaccinia Virus Life Cycle
Temporal
mRNATranscription-Early
ViralGeneTranslation-Early
MovementOfProtein
OutputsmessengerRNA
Participants
mRNATranscription-Early
InputsmessengerRNA
ViralGeneTranslation-Early
MovementOfProtein
Conditions
mRNATranscription-Early
PrespatiallySubsumes Cell VirusCore
ViralGeneTranslation-Early
PostspatiallySubsumes
CellCytoplasm Vitf2
MovementOfProtein
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Evaluation

• 8 biologists were selected, and trained in the
  tools, 4 per team
• The knowledge to be formalised was selected
  (chapter 7 in Alberts)
• The knowledge base was allowed to contain
  pump-priming knowledge
• The biologists entered knowledge , using the
  tools, then tested it against a set of questions,
• Ontology/KB was revised

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Evaluation

• Results (outline)
• A huge amount of data was collected, but analysis
  is complex (IET Inc)
• Domain experts were able to develop ontologies
  after light training
• Knowledge engineers out-perform domain experts in
  ontology construction

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Summary

• Power Tools for ontology development are being
  implemented and tested in the RKF project.
• A Script/Process vocabulary has been developed
  and applied to processes in cell biology,
  covering
• Temporal order
• Participants
• Pre/postconditions
• Repetition