BIRN Ontologies
Ontology Task Force
Topics
• Building the BIRNLex
• Structure of BIRNLex
• BIRN anatomy
• Next steps
The Ontology Task Force: Cross Test Beds
Carol Bean (co-chair), NIH-NCRRMaryann Martone (co-chair), BIRN CCAmarnath Gupta, BIRN CCBill Bug, Mouse BIRNChristine Fennema-Notestine, Morph BIRNJessica Turner, FBIRN•Jeff Grethe, BIRN CC•Daniel Rubin, NCBO•David Kennedy, Morph BIRN
•Provide a dynamic knowledge infrastructure to support integration and analysis of BIRN federated data sets, one which is conducive to accepting novel data from researchers to include in this analysis
•Identify and assess existing ontologies and terminologies for summarizing, comparing, merging, and mining datasets. Relevant subject domains include clinical assessments, assays, demographics, cognitive task descriptions, neuroanatomy, imaging parameters/data provenance in general, and derived (fMRI) data
•Identify the resources needed to achieve the ontological objectives of individual test-beds and of the BIRN overall. May include finding other funding sources, making connections with industry and other consortia facing similar issues, and planning a strategy to acquire the necessary resources
Ontology efforts: July 2005-March 2006
• Created “Bonfire”: a collation of BIRN knowledge sources, e.g., UMLS and Neuronames
– Held workshop in January 2006 for 3 test beds– Each database concept was mapped to unique identifier
• Very useful for “semantic concordance”, i.e., Purkinje cell = Purkinje neuron
– If no entity existed, added entity; assigned unique ID and marked as “uncurated”• Have added ~150 terms to Bonfire
– Problems: • UMLS too inconsistent in relationships and semantic types• most terms lack definitions• Can’t assign attributes to entities• Too complicated for most domain scientists: BIRNLex
• Started development of BIRN ontology “best practices”• Evaluated existing ontology/terminology efforts
– Neuronames– BAMS: Brain Architecture Management System– Mammalian Phenotype Database– BIRN Lex– PATO– Psych Info– FUGO
• Made contact with other major groups working on ontologies to ensure that our efforts would be synergistic with other groups
Ontology Task Force Workshop with NCBO
• National Center for Biomedical Ontologies (NCBO), NCBC, Mark Musen, P. I.– Daniel Rubin from NCBO participates in OTF calls
• Carol Bean arranged for OTF to attend workshop in March 2006– Suzanna Lewis, Barry Smith, Michael Ashburner, Mark Musen, Daniel
Rubin• Educated us on efforts underway at NCBO and vice versa
• Provided their view on ontology “best practices” and what were examples of good ontologies
• Evaluated BIRN’s current efforts
Conclusions from “Fact Finding”
• Well structured ontologies promote integration across ontologies– NCBO has established the ontology foundary http://obofoundary.org
for hosting good ontologies
• Problems in current ontologies:– Mix their metaphors: structure and function– Multiple parents
• Definitions: In a well structure ontology, the human readable definition and the machine processable definition should be the same– Humans: Define according to Aristotle: A is a B which has C
• Recommended reference ontologies: Foundational Model of Anatomy for Structure; Functional Genomics Ontology (FuGO) for experimental process; PATO for phenotype
Use of Foundational Ontologies•National Center for Biomedical Ontologies
Mark Musen, PI
Stanford University
•Facilitates alignment with other ontologies across scales and modalities
•Structure not function (kept them rigorously separate)
•Adopted framework proposed by Barry Smith and colleagues for biological ontologies (Rosse et al., 2005, AMIA proceedings)
•Utilizes basic structure of the Foundational Model of Anatomy
–Regional part
–Constitutional part
–Systemmic part
•Imports existing ontologies where possible, e.g., cell type ontology, Gene ontology cell components
•Open Biomedical Ontologies
Biological Entity
Biological Continuant Biological Occurrent
Dependent Continuant
Independent Continuant
Animal model of Parkinson’s disease
Animal models ofAlzheimer’s disease
Alpha synuclein overexpressor
Alpha synucleinoverexpressor
Alzheimer’s disease
aggregate
Is it or isn’t it?
Strict rules for developing taxonomies
• Behavioral Paradigm– Oddball paradigm
• Auditory oddball paradigm• Visual oddball paradigm
• Telencephalon– Has regional part:
Amygdala
• Working memory paradigm– Serial item
recognition task– Radial maze
• Limbic system– Has systemic part:
Amygdala
Why Aristotle?
• A is a B which has C– Defines class structure– Defines properties
• Electron microscope is a type of microscope which uses electrons to form an image– Microscope
• Electron microscope– Has property
» Image formation
Foundational Model of Anatomy
•Regional part
•Constitutional part
•Systemic part
•Head
•regional part
•Head proper
•Face
•Head
•constitutional part
•Skin
•Muscle
•Skull
Core domain: NeuroanatomyWhat is the hippocampus?
BiologicalReality
Data Technique
Annotator
Data Technique
Analysis Annotator
Biological EntityBiological Entity
FUGO OBI
PATO
Unnamed Entities
• Each biological entity is an unnamed class– Preferred label
• e.g., Biomaterial_Class_1– Preferred label = amygdala– Alternative label = amygdaloid complex– Unique identifier = 000000
Structure of BIRNLex
Bill Bug
The state of Neuroanatomy in BIRN
•Assessed the usage of anatomical terms in each atlas used by BIRN
•Inconsistency in application of terms•Resolution of technique was not considered
•Create standard “atomic” definitions for core brain parts
•Create a volumetric hierarchy
•Provides a basis for accounting for resolution
•Structure not function
•no arguments about whether the amygdala exists functionally
•No arguments about whether the fornix is functionally part of the hypothalamus
•Imported Neuronames hierarchy for volummetric relations among brain parts
•e.g., hippocampal formation has part•Mostly gray matter = dentate gyrus, hippocampus•Mostly white matter = alveus
•Develop consistent application rules:•“My hippocampus” = dentate gyrus + hippocampus”
Putamen
Globus Pallidus
Caudate Nucleus
Thalamus
Ventral Diencephalon
Hippocampus
Cerebral Cortex
Cerebral White Matter
Rock Hyrax brain Llama brain
Can we develop a core high level anatomy that can span species?
Atomic Anatomy
• Modular approach for describing location in the brain• Based on structure of the adult brain
– Resolution ~ equivalent to MRI-based segmentations (~35 structures)
– Entities have to have clear definitions• Definitions will be structural with boundaries and subparts
specified
– Only those areas that have non-controversial correspondences will be identified
• Mouse fornix = Human fornix (Yes!)• M1 = Area 4 (No!)
– Strip function from the mix• Amygdala is just the name of the area, not a statement about its
function
A Man Walks into the Drycleaners…
• Man: I’d like to drop off some shirts for drycleaning• Cleaner: That’s fine, sir.• Man: When will they be ready• Cleaner: 3 days, sir• Man: 3 days! But the name of the shop is “60 Minute
Cleaners”• Cleaner: That’s just the name of the shop, sir.
Amygdala
• What is the amygdala– Mostly gray matter structure
• Where is the amygdala?– Regional part of telencephalon consisting of a non-laminar nucleus
lying anterior to the hippocampal formation in the temporal lobe and anterior to the temporal horn of the lateral ventricle in some species.
• Bona fide boundaries• Fiat boundaries
• What are its parts?– Basal lateral complex– Cortical amygdala– Central amygdala
• What does the amygdala do?
How low can we go?
Cerebral ventricle
• Neuronames: ventricles of the brain: lateral ventricle, third ventricle, fourth ventricle
• Mouse BIRN: ventricular system: lateral ventricle, third ventricle, fourth ventricle, cerebral aqueduct
• Morph BIRN: ventricle: lateral ventricle, third ventricle, fourth ventricle
• BIRNLex: Cerebral ventricle: Does anyone object to including the cerebral aqueduct in our definition of the cerebral ventricle
Cerebral Peduncle
Wikipedia: The cerebral peduncle, by most classifications, is everything in the mesencephalon except the tectum. The region includes the midbrain tegmentum, crus cerebri, substantia nigra and pretectum.
Brain Info
BAMS
Cerebral peduncle
Internal capsule
Corticospinal tract
What do we do?
• Give up?
• Adopt Neuronames definition ?– change Mouse atlas to “crus cerebri”?– Human crus cerebri = mouse cerebral
peduncle
Questions so far
• Telencephalon-diencephalon-mesencephalon-rhombencephalon
• Does thalamus include epithalamus?– Difficult to resolve habenular complex and stria medullaris– Probably don’t want the pineal gland
• Should the cerebellar peduncles be included as cerebellar white matter?
• Cerebral peduncle = crus cerebri or not?• Hippocampus = we prefer hippocampal formation• Do entities like “archicortex”, “archistriatum” serve a
purpose? What about neostriatum? What about “limbic lobe”?
What should we do?
• Adopt standard definitions• Define a volumetric hierarchy• Use BIRNLex or else define existing structures
in terms of BIRNLex entities– e.g., QAHippocampus = dentate gyrus +
hippocampus proper + alveus + subiculum + fimbria– MBATHippocampus = dentate gyrus + hippocampus
proper + alveus– Fsthalamus = thalamus + habenular nuclei + stria
medullaris
• Adopt spatial qualifiers– Overlaps with, coextensive with, contained in – Look to GIS???
Where’s the function?
• No simple mapping between brain structure and function– Most of our structures are artificial, based on
boundaries that we can see or easily reveal• Remember the extended amygdala?
• Most biological entities do not fit into “is a” hierarchies
• Provide formalized way of describing “brain voxels???” to facilitate comparison
Next steps
• Finish the definitions• Define the BIRN Core entities• Build the ontology
– Assign part of’s– Create an ontology for properties of brain regions
• Important for homology
• How should the ontology be “served”?• Community involvement
– BIRN “Wikipedia”?
• Additional core domains– Phenotype (analysis)
BIRN-Lex: What’s next?
• Image content– Anatomical regions
• Neuronames (FMA)
– Cell components• GO• Ontology for subcellular anatomy of
nervous system
– Signal• Protein, RNA, DNA
– Relationship of the label to the thing
– Relationship among these entities
• Activation
• Image Analysis– Segmentation
• Image Processing• Image data
– Image type– resolution
• Phenotype (analysis result)– Behavioral– Biochemical– Genetic– Cognitive– Morphometric– “environmental”
• Instruments– MRI– Microscopes
• Optical microscope
• Electron microscope
• Subject
• Experimental design
• Experimental platform
• Specimen preparation– Fixation– Contrast agent
• Assay– Behavioral
– Cognitive
– Biochemical etc
Comparing animal models against disease
Human holo-prosencephaly
Zebrafishshh
Zebrafishoep
Environment
Algorithm
Hypothesis
Objective
Protocol
Study Factor
Study Report
Study Design
Dependent Factor Independent Factor
Conclusion
Publication
Correlational Study Descriptive Study Experimental Study
Function
Software
Part of Instrument
Part of Microscope
Microscope Lens
Part of MR Scanner
Consumable
Reagent
Physical Datum
Instrument
Platform
Consists of
Utilizes
Investigator
Role
Study Object
Study Organism Study Population
Specimen
Study GroupGross Dissection Cell Fraction
Study Sample
Contained In
OrganCell
Sample Preparation
Is of Type
In Vivo
Ex Vivo
In Vitro
Post Mortem
InstitutionEvent
Time Point
Time Interval
Unit of Measure
Analysis Protocol Preparation Protocol
Cardinal Part of Protocol
Consists of
CP Immunolabeling Protocol
Incubation with Primary Antibody
Project
Measuring
Measurement
Observing
Observation
Setting Parameter Value
Specimen Preparation Process
Fixing
Session
Longitudinal StudyTime Independent Study
Disease Progression
Study Episode
Consists of
Data Collection Episode
Investigation
Study
Consists of
Consists of
Consists of
Consists of
Consists of
Results In
Produced Through
Participates In
Has
SiteLocated At
Participates In
Results In
Results In
Has
HasReview Board
HasProtocol Approval
Provides
Required By
Results From
Results From
Study Protocol
Has
Experimental Condition
Has
Informs
Has
Produced ViaResults In
Has
BIRN Ontology for the Multi-Scale Investigation of Neurological DisordersBIRN Ontology for the Multi-Scale Investigation of Neurological Disorders
FuGO Entity
FuGO/BIRN Conflict
BONFIRE Entity
“Is A”
Relation
“ModifiesRelation”
RelationApplies to Entity
RelationApplies to Entity and Narrower
LegendLegend
Study Group
Session
Consists of
Investigation
Study
Consists of Consists of
Consists of
Participates In
Results In