BIRNLex and Associated Tools Maryann Martone, Bill Bug, Jeff Grethe 2007

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) Imports existing ontologies where possible, e.g., cell type ontology, Gene ontology cell components Ontology for Biomedical Investigation PATO Biological Entity Biological Continuant Biological Occurrent Dependent Continuant Independent Continuant

Animal model of Parkinson’s disease Animal models of Alzheimer’s disease Alpha synuclein overexpressor Alpha synuclein overexpressor 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

Foundational Model of Anatomy Regional part Constitutional part Systemic part Head regional part Head proper Face Head constitutional part Skin Muscle Skull

Core domain: Neuroanatomy What is the hippocampus?

DataTechnique AnalysisAnnotator Biological Entity FUGO OBI PATO BIRN

Structure of BIRNLex Protégé 3.2 OWL: Web Ontology Language Several different domains: Cognitive behaviors Human/non-human Neuroanatomy Biomedical Investigation Instruments, protocols, data MRI glossary Organisms Curatorial metadata (adopted by OBI community!) Definition Curation status Source reference Unique identifiers

Where is BIRNLex?

Browsing BIRNLex: OWLDocs nbirn.net/birnlex/1.0/OWLdocs

Why Aristotle? A is a B which has C –Defines class structure –Defines properties Electron microscope is a type of microscope which uses electrons rather than photons to form an image –Microscope Electron microscope –Has property »Image formation

Coming Soon… BIRNLex is in the process of being added to NCBO’s Bio PortalBio Portal Search and display BIRNLex is being imported into Bonfire Programmatic access MBAT Mediator

Contributing to BIRNLex Ontology is maintained and curated by the Ontology Task Force We welcome active contribution by BIRN community Curation sessions Recommend new domains/ontologies Submit/request terms Send OTF an or spreadsheet Community comment Wiki

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”

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

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 Internal capsule Corticospinal tract

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. mesencephalonmidbrain tegmentum crus cerebrisubstantia nigrapretectum Brain Info BAMS

What should we do? Adopt standard definitions –Be particularly careful when mapping microarray data to MBAT: 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 –GIS has defined spatial qualifiers like contained in, overlaps with, etc.

Next steps Finish the definitions Finish core anatomy –Priority: Badea regions Apply BIRNLex entities in databases, atlases and XCEDE Assemble instrument hierarchies for OBI Build the ontology –Assign part of’s –Create an ontology for properties of brain regions Important for homology Additional core domains –Phenotype (analysis)

New Tools for Annotation of BIRN databases Brian Sanders, Vadim Astakov, Jeff Grethe

PATO: Phenotype and Trait Ontology GenotypeEntityAttributeValue npogutstructuredysplastic gutrelative sizesmall r210retinapatternirregular brainstructurefused tm84d/v pattern formation qualitativeabnormal blood islandsrelative numbernumber increased Bsb[2]elongation of arista literal processarrested C-alpha[1D]adult behaviourbehavioral activityuncoordinated 2003 trial data: FB & ZFIN Way of expressing complex phenotypes in way that is more scientifically “sound” BIRN provides valuable test cases for PATO BIRN data immediately becomes interoperable with Zebrafish and fly communities

Expressing complex BIRN traits in PATO Bill has begun developing use cases for PATOuse cases MM to develop image-based test cases using multiscale data Begin working with annotation tools developed by PATO Phenote Develop Phenote plug in for spatial annotation of image data Work with BIRN CC to develop tools to compare animal models to human neurological disease