Download - Application of OBO Foundry Principles in GO Chris Mungall Lawrence Berkeley Labs NCBO GO Consortium
Application of OBO Foundry Principles in GO
Chris MungallLawrence Berkeley Labs
NCBOGO Consortium
The GO is 3 ontologies
• Molecular function (MF)• Biological Process (BP)• Cellular component (CC)
The GO is 3 orthogonal ontologies
• Molecular function– (a kind of dependent continuant)
• Biological Process– (a kind of occurrent)
• Cellular component– (a kind of independent continuant)
The GO is 3 orthogonal ontologies of canonical
biology • Molecular function
– (a kind of dependent continuant)
• Biological Process– (a kind of occurrent)
• Cellular component– (a kind of independent continuant)
oncogenesisX
fin regeneration yesacquisition of nutrientsfrom hostyes
The GO is 3 orthogonal canonical species-neutral
ontologies• Molecular function
– many core functions• Biological Process
– core shared processes (e.g. transcription)– processes specific to organism types (e.g.
fin development, fly courtship behaviour)
• Cellular component– prokaryotes and eukaryotes
part ofthepart_oftreein GO
Granularity of the GO
Function Process Continuant
Molecular GO-MF
GO-BP GO-CC
(Sub?)Cellular
GO-BP GO-CC
Organismal GO-BP
The GO is an ontology, with rich terminological
features• GO ‘terms’ are actually representations of types
(aka kinds, universals, classes)– The actual terms (i.e. the phrases used by biologists)
are attached to the representations of types as names and synonyms
• synonyms have linguistic relations to the GO types– exact, broad, narrow, related
• distinct from ontological relations between GO types– is_a, part_of
• GO is moving to genus-differentia style definitions– Many definitions are still dictionary-style,
terminological• describe how the term is used
Genus differentia definitions
central nervous system morphogenesisGenus: morphogenesisDifferentia: has_outcome central nervous system
The process by which the anatomical structure of the central nervous system is generated and organized
The GO is both reference and application ontology
• The same artefact (i.e. file) is used for both ontology editing and data annotation
• This has worked reasonably well until now• We may encourage making a distinction
– application views (aka GO slims) • currently only used to present a very small subset
of GO• consider wider use for extracting most of ontology
Relations in GO (current)
• part_of– conforms to RO
• X part_of Y: all Xs are part_of some Y (for the entirety of the duration of the existence of the X)
– e.g. nucleus part_of cell (all nuclei are always part_of a cell, not all cells have a nucleus as part)
• for both continuants and processes– no ordering for processes
• is_a– sort-of conforms to RO
• X is_a Y: all Xs are Ys (for the entirety of Xs existence)• but there are issues with is_a in GO:
– is_a incompleteness– is_a polyhierarchies
is a has issues
• Not all GO types have is_a parents– not a problem in MF– fixed in CC (July 2006)– being fixed in BP (Sept 2006: right now, here in
Seattle)
• Still a contentious issue?– is_a completion requires new high-level types
in ontology– perceived as being too abstract by biologists– simple solution: application ontology
• remove high level terms in annotation view
is_a polyhierarchies
• is_a diamonds cause problems– tangled DAGs, easy to make mistakes
• Source of problems typically due to multiple axes of classification– e.g. due to composite terms
• Solution:– Genus - differentia (aristotelian) definitions
• aka cross-products [Hill et al]
– Always a single genus• choose consistent axis of classification
– Allow classifier/reasoner to provide different views of ontology
a tangled hierarchyin GO
problem:mixes (at least)two axes ofclassification
biosynthesisis_ametabolism
cysteineis_aserine family amino acidis_aamino acidis_aamine
cysteineis_aserine family amino acidis_aamino acidis_aserine
The solution: separate the axes
cysteine biosynthesis (GO)Genus: biosynthesisDifferentia: has_outcome cysteine
biosynthesis (GO)
metabolism (GO)
cysteine (ChEBI)
serine family amino acid (ChEBI)
computablegenus-differentiadefinition
Compute the subsumption DAG from the definition
cysteine biosynthesis (GO)Genus: biosynthesisDifferentia: has_outcome cysteine
cysteine metabolism (GO)
serine family amino acid biosynthesis (GO)
the DAG isrequiredfor applicationssuch as annotationsearch
Pre- and post- composition
• References to types can be pre-composed in ontology, prior to annotation– Ontology editor creates term, with ID– Use reasoners to classify the DAG
automatically
• References to types can be post-composed (created on the fly) at annotation time– No term with ID is created
• Computationally, it makes no difference– provided we adhere to the genus-differentia
formalism
OBO Foundry practices and pre-composition
• Pre-composition of terms in the ontology is good as it creates a map of biological reality, linking foundry ontologies– within reason
Examples
• GO Biological Process x OBO Cell– neuron migration– cone cell fate specification– T cell homeostasis– erythrocte degranulation
• OBO Cell is species-neutral
Current status
• The ability to effectively created computationally visible genus-differentia definitions is new to most OBO ontologies
• Soon to be created:– SO (many terms now done)– GO-BP definitions referencing OBO-Cell– OBO Disease definitions referencing FMA– And more…
• Difficult:– GO-BP and ChEBI (chemical entities)– GO-BP and anatomy (we need CARO!)
development in GO (current)
neural tube formation
neural tube development
neural plate formation
neural plate development
GO
part_of
neural plate morphogenesis
(is_a not shown)
development in GO (future)
presumptive spinal cord
neural plate
neural keel
neural rod
neural tube
spinal cord
transformation_of
neural tube formation
neural tube development
neural plate formation
neural plate development
has_participant
AO GO
part_of
neural tube formationGenus: tube formation Differentia: has_outcome neural tube
neural plate morphogenesis