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CARO 2.0 & FUNCARO
David Osumi-Sutherland
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Review of CARO (v1)
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Many definitions are complicated and opaque:
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No explicit disjointness declarations
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‘anatomical group: “[An] anatomical structure consisting of at
least two non-overlapping organs, multi-tissue aggregates or
portion of tissues or cells of different types that does not
constitute an organism, organ, multi-tissue aggregate, or portion
of tissue.”
despite assertion of pairwise disjointness in paper.
Rigid single inheritance
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Lack of necessary and sufficient definitions means no way to
manage multiple classification
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Problems with existing
implementations
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Assuming pairwise disjointness in CARO(v1):
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Classified as both material and immaterial entities:
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Classified as both cell and ‘portion of tissue’
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pyloric chamber; scale
adult sensory neuron
disjointness violations hidden by enforced single
inheritance?
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The following are classified under ‘organism subdivision’
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'unicellular gland’; scale; vent
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Aims for CARO v2.0
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Clear definitions made for biologically defensible reasons or
to ensure good modeling practice.
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distinctions must be readily understandable by biologists
and commonly distinguishable:
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classification depending on criteria for which little data exists
should be avoided.
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Definitions should be fomalised so that auto-classification by
reasoners can be used in place of hand classification.
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Disjoint declarations must be present for error checking
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Approach for CARO v2
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Master version
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in OWL
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imports relevant BFO and RO classes and relations (object
properties)
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Provide an OBO translation, although likely to have more
limited semantics
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Focus on defining differentia
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potentially => safe multiple inheritance.
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Fundamental, disjoint classes
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material vs immaterial
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Examples
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potential importance includes
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lumen of stomach (space) vs wall of
stomach (structure) vs the outside
surface of the stomach (boundary with
the body cavity; a 2D structure)
error checking
immaterial structures can’t be
 site of gene expression
 site of functions/processes requiring
cells
formalization:
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material anatomical entity: has_quality
some mass (PATO)
DisjointWith immaterial anatomical
entity
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amorphous vs has shape
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Example
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Importance includes
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blood vs tibia
error checking, in case shape
quality mistakenly asserted or
implied for ‘anatomical
substance’
anatomical structure:
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Material anatomical entity that is a
single connected structure with
inherent 3D shape generated by
coordinated expression of the
organism's own genome.
DisjointWith ‘organism substance’
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cellularization state
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Disjoint classes:
• acellular (e.g.- cuticle)
• cell (e.g. guard cell)
• multicellular (e.g. upper
epidermis)
• multi-cell component (fanshaped body)
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Importance
• Error checking
• Cells are a fundamental unit of
structure in biology, CARO
should reflect this.
• Acellular structure:
• Can’t be site of gene
expression
• Can’t be site of
functions/processes
requiring cells
Fan shaped body (synaptic neuropil)
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cellularization state
• formalization:
• cell – import class from CL
• acellular anatomical
structure
• EquivalentTo ‘anatomical
structure’ and (has_part
only not (cell or ‘cell
part’))
• multicellular anatomical
structure
• EquivalentTo: ‘anatomical
structure’ and
has_component min 2 cell
• multi-cell part structure
• EquivalentTo: ‘anatomical
structure’ and
has_component min 2
‘cell part’ and has_part
only not cell
Fan shaped body (synaptic neuropil)
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connected vs not
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anatomical group:
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anatomical structure
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‘anatomical structure’ DisjointWith
‘anatomical group’
PATO quality – connected ?
Examples
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“A material anatomical entity consisting of a
single connected whole.”
Formalisation
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“A material anatomical entity consisting of
multiple parts that are not physically
connected to each other.”
immune system vs vasculature
Importance
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clarity about boundaries
Making good practice clear
 use class reasoning where possible, avoid
making anatomical groups that are
mereological sums of other classes (e.g.use finger not 'set of fingers')
Useful in some mereological reasoning
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Types of anatomical group
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anatomical cluster
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def: “anatomical group whose
members are in close
proximity to each other.”
aligned anatomical group
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“anatomical group whose
members are arranged in a
line”
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From the organism down:
organisms and their subdivisions.
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organism
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organism
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def: “An individual member of a species.”
How to classify?
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Make agnostic about unicellular vs
multicellular.
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This avoids confusion about fertilized egg
stage of multicellular organisms.
anatomical structure?
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rules out separated clones (e.g.
cuttings in plants; which is probably
OK)
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difficult for Dicty (but then again, Dicty
is difficult!)
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Anatomical system
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Examples:
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nervous system; immune system; musculo-skeletal system
attempt at formalization:
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the (mereological) sum of all X in a single organism,
 Where X can be:
 a functionally defined class (see FUNCARO)
 a set of high level anatomical classes
 e.g.- vertebrate muscloskeletal system might be:
 The mereological sum of all muscles, ligaments, bones,
tendons, cartillage and joints
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connected system
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An anatomical system that is
connected
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Examples:
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vertebrate circulatory system
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nervous system
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Organism subdivision
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Examples:
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insect head; insect abdominal
segment; insect leg
Some necessary conditions
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has a contiguous integumental
boundary
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has parts of multiple organ
systems
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types of multicellular structure
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Tissue
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tissue:
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“Multicellular anatomical structure that consists of many cells of
one or a few types, arranged in an extracellular matrix such that
their long-range organisation is at least partly a repetition of their
short-range organisation.”
tissue types
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by cell type
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request PATO qualities?
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lamina; mesenchymal, others?
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cell cluster organ
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def: “A multicellular anatomical strucure consisting of a few
cells of various types which forms a discrete structure with a
largely bona fide boundary.”
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Examples
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ommatidium; neuromast (of lateral line)
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compound cell cluster organ
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def: “An anatomical structure consisting of multiple cell
cluster organs and that has a largely bona-fide boundary.”
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Examples:
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compound eye
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FUNCARO – a functional extension
to CARO
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Extends CARO with functional classed defined using
relations to GO process terms
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Aims
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A set of logically defined upper level terms for classifying
anatomical structures by function.
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A reference set of design patterns for specifying the functions of
anatomical structures using GO process terms.
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Relations for defining function
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capable_of
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expands to: bearer_of some (realised_by only ?P)
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domain: ‘continuant’
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range: ‘process’
capable_of_part_of
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expands_to: bearer_of some (realized_by only (part_of some ?P)
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domain: ‘continuant’
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range: ‘process’
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property chain: bearer_of o part_of -> bearer_of_part_of
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If X bearer_of Y and Y part_of Z then X bearer_of_part_of Z
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Terms for classifying by sensory
function
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Gene Ontology classification of sensory processes:
+ Some necessary and sufficient
definitions
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*Strictly speaking, ‘some’ is a fudge. Better to use expanded forms in OWL?
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Autoclassification
capable_of
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Functional systems – autopopulating partonomies
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functional system
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respiratory system
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EquivalentTo: ‘functional system’ that capable_of some ‘respiratory
gaseous exchange’
respiratory system component
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A material anatomical entity defined by the common function of its
component parts. These parts may or may not be connected to form
a single structure.
EquivalentTo: ‘anatomical structure’ that capable_of some ‘respiratory
gaseous exchange’
SubClassOf: part_of some ‘respiratory system’
‘tracheolar cell’
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SubClassOf capable_of some ‘respiratory gaseous exchange’
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Auto-populating respiratory
system partonomy
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Inferring capable_of_part_of
If X 'capable of' Y and Y part_of Z then X capable_of_part_of Z
part_of
capable_of_part_of
capable_of
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A class for populating the
partonomy of the olfactory system
Note – in OWL this could be done without making this ugly class:
(‘anatomical structure’ that capable_of_part_of some ‘sensory
perception of smell’) SubClassOf (part_of some ‘olfactory system’)
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Challenges for FUNCARO
- GO
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Many potentially useful GO terms reference anatomical
systems:
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immune response: “Any immune system process that functions in
the calibrated response of an organism to a potential internal or
invasive threat.”
Granularity restrictions on GO terms may cause problems
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cellular process vs multicellular organismal process
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e.g.- detection of stimulus involved in sensory perception :
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“The series of events involved in sensory perception in which a
sensory stimulus is received by a cell and converted into a
molecular signal.”
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Please download, try and comment
 http://code.google.com/p/caro2/
 use
the issue tracker to comment
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Acknowledgments
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Michael Ashburner
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Chris Mungall
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Melissa Haendal
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Matt Yoder
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Andy Deans