+

CARO 2.0 & FUNCARODavid Osumi-Sutherland

+Review of CARO (v1)

Many definitions are complicated and opaque: ‘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.”

No explicit disjointness declarations despite assertion of pairwise disjointness in paper.

Rigid single inheritance Lack of necessary and sufficient definitions means no way

to manage multiple classification

+Problems with existing implementations Assuming pairwise disjointness in CARO(v1):

Classified as both material and immaterial entities: pyloric chamber; scale

Classified as both cell and ‘portion of tissue’ adult sensory neuron

disjointness violations hidden by enforced single inheritance? The following are classified under ‘organism subdivision’

'unicellular gland’; scale; vent

+Aims for CARO v2.0

Clear definitions made for biologically defensible reasons or to ensure good modeling practice.

distinctions must be readily understandable by biologists and commonly distinguishable: classification depending on criteria for which little data

exists should be avoided.

Definitions should be fomalised so that auto-classification by reasoners can be used in place of hand classification.

Disjoint declarations must be present for error checking

+Approach for CARO v2

Master version in OWL imports relevant BFO and RO classes and relations (object

properties)

Provide an OBO translation, although likely to have more limited semantics

Focus on defining differentia potentially => safe multiple inheritance.

+

Fundamental, disjoint classes

+material vs immaterial Examples

lumen of stomach (space) vs wall of stomach (structure) vs the outside surface of the stomach (boundary with the body cavity; a 2D structure)

potential importance includes error checking immaterial structures can’t be

site of gene expression site of functions/processes requiring

cells

formalization: material anatomical entity: has_quality

some mass (PATO) DisjointWith immaterial anatomical

entity

+amorphous vs has shape Example

blood vs tibia

Importance includes error checking, in case shape

quality mistakenly asserted or implied for ‘anatomical substance’

anatomical structure: 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’

+cellularization state• Disjoint classes:

• acellular (e.g.- cuticle)• cell (e.g. guard cell)• multicellular (e.g. upper epidermis)• multi-cell component (fan-shaped

body)

• 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)

+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)

+connected vs not anatomical group:

“A material anatomical entity consisting of multiple parts that are not physically connected to each other.”

anatomical structure “A material anatomical entity consisting of a

single connected whole.”

Formalisation ‘anatomical structure’ DisjointWith

‘anatomical group’ PATO quality – connected ?

Examples immune system vs vasculature

Importance 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

+Types of anatomical group anatomical cluster

def: “anatomical group whose members are in close proximity to each other.”

aligned anatomical group “anatomical group whose

members are arranged in a line”

+

From the organism down:organisms and their subdivisions.

+organism organism

def: “An individual member of a species.”

How to classify? Make agnostic about unicellular vs

multicellular. This avoids confusion about fertilized

egg stage of multicellular organisms. anatomical structure?

rules out separated clones (e.g. cuttings in plants; which is probably OK)

difficult for Dicty (but then again, Dicty is difficult!)

+Anatomical system

Examples: nervous system; immune system; musculo-skeletal system

attempt at formalization: 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

+connected system

An anatomical system that is connected

Examples: vertebrate circulatory system nervous system

+Organism subdivision Examples:

insect head; insect abdominal segment; insect leg

Some necessary conditions has a contiguous integumental

boundary has parts of multiple organ

systems

+

types of multicellular structure

+Tissue

tissue: “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 by cell type request PATO qualities?

lamina; mesenchymal, others?

+cell cluster organ

def: “A multicellular anatomical strucure consisting of a few cells of various types which forms a discrete structure with a largely bona fide boundary.”

Examples ommatidium; neuromast (of lateral line)

+compound cell cluster organ

def: “An anatomical structure consisting of multiple cell cluster organs and that has a largely bona-fide boundary.”

Examples: compound eye

+FUNCARO – a functional extension to CARO Extends CARO with functional classed defined using

relations to GO process terms Aims

A set of logically defined upper level terms for classifying anatomical structures by function.

A reference set of design patterns for specifying the functions of anatomical structures using GO process terms.

+Relations for defining function

capable_of expands to: bearer_of some (realised_by only ?P) domain: ‘continuant’ range: ‘process’

capable_of_part_of expands_to: bearer_of some (realized_by only (part_of

some ?P) domain: ‘continuant’ range: ‘process’ property chain: bearer_of o part_of -> bearer_of_part_of

If X bearer_of Y and Y part_of Z then X bearer_of_part_of Z

+Terms for classifying by sensory function Gene Ontology classification of sensory processes:

+Some necessary and sufficient definitions

*

*Strictly speaking, ‘some’ is a fudge. Better to use expanded forms in OWL?

+Autoclassification

capable_of

+Functional systems – auto-populating partonomies functional system

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.

respiratory system EquivalentTo: ‘functional system’ that capable_of some ‘respiratory

gaseous exchange’

respiratory system component EquivalentTo: ‘anatomical structure’ that capable_of some ‘respiratory

gaseous exchange’ SubClassOf: part_of some ‘respiratory system’

‘tracheolar cell’ SubClassOf capable_of some ‘respiratory gaseous exchange’

+Auto-populating respiratory system partonomy

+

capable_of_part_of

If X 'capable of' Y and Y part_of Z then X capable_of_part_of Z

capable_of

part_of

Inferring capable_of_part_of

+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’)

+

+Challenges for FUNCARO - GO

Many potentially useful GO terms reference anatomical systems: 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 cellular process vs multicellular organismal process e.g.- detection of stimulus involved in sensory perception :

“The series of events involved in sensory perception in which a sensory stimulus is received by a cell and converted into a molecular signal.”

+Please download, try and comment

http://code.google.com/p/caro2/use the issue tracker to comment

+Acknowledgments

Michael Ashburner Chris Mungall Melissa Haendal Matt Yoder Andy Deans