MGED Ontology: An Ontology of Biomaterial Descriptions for Microarrays
description
Transcript of MGED Ontology: An Ontology of Biomaterial Descriptions for Microarrays
![Page 1: MGED Ontology: An Ontology of Biomaterial Descriptions for Microarrays](https://reader035.fdocuments.us/reader035/viewer/2022062519/56814f36550346895dbcd303/html5/thumbnails/1.jpg)
MGED Ontology:An Ontology of Biomaterial Descriptions for Microarrays
Microarray Data Analysis and Management:
Bio-ontologies for Microarrays
EMBL-EBI, Hinxton, Cambridge, UK
Dec. 5, 2001
Chris Stoeckert, U. Penn
![Page 2: MGED Ontology: An Ontology of Biomaterial Descriptions for Microarrays](https://reader035.fdocuments.us/reader035/viewer/2022062519/56814f36550346895dbcd303/html5/thumbnails/2.jpg)
Ontology Usage for Genes in EpoDB
• EpoDB is a prototype system of genes expressed during erythropoiesis
• Built before microarrays were readily available
• Illustrate usage of an ontology of gene parts and controlled vocabularies of gene (and gene family) names
![Page 3: MGED Ontology: An Ontology of Biomaterial Descriptions for Microarrays](https://reader035.fdocuments.us/reader035/viewer/2022062519/56814f36550346895dbcd303/html5/thumbnails/3.jpg)
EpoDB “Gene Ontology”
![Page 4: MGED Ontology: An Ontology of Biomaterial Descriptions for Microarrays](https://reader035.fdocuments.us/reader035/viewer/2022062519/56814f36550346895dbcd303/html5/thumbnails/4.jpg)
http://www.cbil.upenn.edu/EpoDB
Stoeckert, Salas, Brunk, Overton (1999) Nucl. Acids Res. 26:288
![Page 5: MGED Ontology: An Ontology of Biomaterial Descriptions for Microarrays](https://reader035.fdocuments.us/reader035/viewer/2022062519/56814f36550346895dbcd303/html5/thumbnails/5.jpg)
EpoDB Gene Landmark Query
![Page 6: MGED Ontology: An Ontology of Biomaterial Descriptions for Microarrays](https://reader035.fdocuments.us/reader035/viewer/2022062519/56814f36550346895dbcd303/html5/thumbnails/6.jpg)
What is an ontology?(In the computer science not philosophy sense)
• An ontology is a specification of concepts that includes the relationships between those concepts.
• Removes ambiguity. Provides semantics and constraints.
• Allows for computational inferences and reliable comparisons
![Page 7: MGED Ontology: An Ontology of Biomaterial Descriptions for Microarrays](https://reader035.fdocuments.us/reader035/viewer/2022062519/56814f36550346895dbcd303/html5/thumbnails/7.jpg)
Types of Ontologies• Taxonomy
– Tree structure. IS-A hierachy– Variants - Gene Ontology (DAG)
• Frame-based (object-oriented)– Classes and attributes– EcoCyc
• Description logic (DL)– Reasoning about concept (class) relationships– Combine terms with constraints (sanctioning)– GRAIL (GALEN, TAMBIS)
• Ontology Inference Layer (OIL)– Combines Frames and DLs– Uses Web standards XML and RDF
![Page 8: MGED Ontology: An Ontology of Biomaterial Descriptions for Microarrays](https://reader035.fdocuments.us/reader035/viewer/2022062519/56814f36550346895dbcd303/html5/thumbnails/8.jpg)
Taxonomy• Terms for common usage
– Homo sapiens, not human, not homo sapeins– NCBI ID = 9606
• Hierarchy provides unambiguous levels of equivalence– Homo sapiens and Mus musculus are of the class
Mammalia but Drosophila melanogaster is not.
• Can use taxonomic hierarchies for other types of information– e.g., Human Developmental Anatomy (U. of Edinburgh)
![Page 9: MGED Ontology: An Ontology of Biomaterial Descriptions for Microarrays](https://reader035.fdocuments.us/reader035/viewer/2022062519/56814f36550346895dbcd303/html5/thumbnails/9.jpg)
Microarray Information to be Captured
Figure from:David J. Duggan et al. (1999) Expression Profiling using cDNA microarrays. Nature Genetics 21: 10-14
![Page 10: MGED Ontology: An Ontology of Biomaterial Descriptions for Microarrays](https://reader035.fdocuments.us/reader035/viewer/2022062519/56814f36550346895dbcd303/html5/thumbnails/10.jpg)
Tables Describing Samples in RAD (RNA Abundance Database)
Experiment
ExpGroupsGroups RelExperiments
Exp.ControlGenes
ControlGenes
HybridizationConditions
Label
Sample
TreatmentDiseaseDevel. Stage
ExperimentSample
Taxon
Anatomy
![Page 11: MGED Ontology: An Ontology of Biomaterial Descriptions for Microarrays](https://reader035.fdocuments.us/reader035/viewer/2022062519/56814f36550346895dbcd303/html5/thumbnails/11.jpg)
CBIL Anatomy Hierarchy
![Page 12: MGED Ontology: An Ontology of Biomaterial Descriptions for Microarrays](https://reader035.fdocuments.us/reader035/viewer/2022062519/56814f36550346895dbcd303/html5/thumbnails/12.jpg)
Anatomy Table Used by RAD
![Page 13: MGED Ontology: An Ontology of Biomaterial Descriptions for Microarrays](https://reader035.fdocuments.us/reader035/viewer/2022062519/56814f36550346895dbcd303/html5/thumbnails/13.jpg)
Usage of Anatomy Hierarchy to Query RAD
![Page 14: MGED Ontology: An Ontology of Biomaterial Descriptions for Microarrays](https://reader035.fdocuments.us/reader035/viewer/2022062519/56814f36550346895dbcd303/html5/thumbnails/14.jpg)
Standardisation of Microarray Data and Annotations -MGED Group
The MGED group is a grass roots movement initially established at the Microarray Gene Expression Database meeting MGED 1 (14-15 November, 1999, Cambridge, UK). The goal of the group is to facilitate the adoption of standards for DNA-array experiment annotation and data representation, as well as the introduction of standard experimental controls and data normalisation methods. Members are from around the world in academia, government, and industry.
http://www.mged.org
![Page 15: MGED Ontology: An Ontology of Biomaterial Descriptions for Microarrays](https://reader035.fdocuments.us/reader035/viewer/2022062519/56814f36550346895dbcd303/html5/thumbnails/15.jpg)
MGED Working Groups
• Annotation: Experiment description and data representation standards (Alvis Brazma, EMBL-EBI)
• Format: Microarray data XML exchange format (Paul Spellman, UC Berkeley)
• Ontology: Ontologies for sample description (Chris Stoeckert, U Penn)
• Normalization: Normalization, quality control and cross-platform comparison (Gavin Sherlock, Stanford U)
![Page 16: MGED Ontology: An Ontology of Biomaterial Descriptions for Microarrays](https://reader035.fdocuments.us/reader035/viewer/2022062519/56814f36550346895dbcd303/html5/thumbnails/16.jpg)
MGED Documents
• Annotation -> Minimal Information About a Microarray Experiment (MIAME)– What should go into a microarray database– Brazma et al. Nature Genetics 29:365-371, 2001
• Format -> Microarray Gene Expression (MAGE) Object Model and XML DTD– How microarray databases will talk to each other
![Page 17: MGED Ontology: An Ontology of Biomaterial Descriptions for Microarrays](https://reader035.fdocuments.us/reader035/viewer/2022062519/56814f36550346895dbcd303/html5/thumbnails/17.jpg)
Relationship of MGED Efforts
MAGEMIAMEDB
MIAMEDBExternal
Ontologies/CVs
MGED Ontology
AnnotationFormatOntologies External Internal
Ontologies provide common terms and their definitions for describing microarray experiments.
![Page 18: MGED Ontology: An Ontology of Biomaterial Descriptions for Microarrays](https://reader035.fdocuments.us/reader035/viewer/2022062519/56814f36550346895dbcd303/html5/thumbnails/18.jpg)
MGED Ontology Working Group Goals
1. Identify concepts
2. Collect available controlled vocabularies and ontologies for concepts
3. Define concepts
4. Formalize concept relationships
![Page 19: MGED Ontology: An Ontology of Biomaterial Descriptions for Microarrays](https://reader035.fdocuments.us/reader035/viewer/2022062519/56814f36550346895dbcd303/html5/thumbnails/19.jpg)
http://www.cbil.upenn.edu/Ontology/
![Page 20: MGED Ontology: An Ontology of Biomaterial Descriptions for Microarrays](https://reader035.fdocuments.us/reader035/viewer/2022062519/56814f36550346895dbcd303/html5/thumbnails/20.jpg)
SpeciesResources
![Page 21: MGED Ontology: An Ontology of Biomaterial Descriptions for Microarrays](https://reader035.fdocuments.us/reader035/viewer/2022062519/56814f36550346895dbcd303/html5/thumbnails/21.jpg)
![Page 22: MGED Ontology: An Ontology of Biomaterial Descriptions for Microarrays](https://reader035.fdocuments.us/reader035/viewer/2022062519/56814f36550346895dbcd303/html5/thumbnails/22.jpg)
ConceptDefinitions
![Page 23: MGED Ontology: An Ontology of Biomaterial Descriptions for Microarrays](https://reader035.fdocuments.us/reader035/viewer/2022062519/56814f36550346895dbcd303/html5/thumbnails/23.jpg)
![Page 24: MGED Ontology: An Ontology of Biomaterial Descriptions for Microarrays](https://reader035.fdocuments.us/reader035/viewer/2022062519/56814f36550346895dbcd303/html5/thumbnails/24.jpg)
MGED Ontology Working Group Goals
1. Identify concepts
2. Collect available controlled vocabularies and ontologies for concepts
3. Define concepts
4. Formalize concept relationships
![Page 25: MGED Ontology: An Ontology of Biomaterial Descriptions for Microarrays](https://reader035.fdocuments.us/reader035/viewer/2022062519/56814f36550346895dbcd303/html5/thumbnails/25.jpg)
Usage of Concepts and Resources for Microarrays
• MIAME glossary– Provide definitions for types of information
(concepts) listed in MIAME
• MIAME qualifier, value, source– Provide pointers to relevant sources that can be
used to
![Page 26: MGED Ontology: An Ontology of Biomaterial Descriptions for Microarrays](https://reader035.fdocuments.us/reader035/viewer/2022062519/56814f36550346895dbcd303/html5/thumbnails/26.jpg)
sample source and treatment ID as used in section 1organism (NCBI taxonomy)additional "qualifier, value, source" list; the list includes:
cell source and type (if derived from primary sources (s))sexagegrowth conditionsdevelopment stageorganism part (tissue)animal/plant strain or linegenetic variation (e.g., gene knockout, transgenic variation)individualindividual genetic characteristics (e.g., disease alleles, polymorphisms)disease state or normaltarget cell typecell line and source (if applicable)in vivo treatments (organism or individual treatments)in vitro treatments (cell culture conditions)treatment type (e.g., small molecule, heat shock, cold shock, food deprivation)compoundis additional clinical information available (link)separation technique (e.g., none, trimming, microdissection, FACS)
laboratory protocol for sample treatment
MIAME Section on Sample Source and Treatment
![Page 27: MGED Ontology: An Ontology of Biomaterial Descriptions for Microarrays](https://reader035.fdocuments.us/reader035/viewer/2022062519/56814f36550346895dbcd303/html5/thumbnails/27.jpg)
Excerpts from a Sample Descriptioncourtesy of M. Hoffman, S. Schmidtke, Lion BioSciences
Organism: mus musculus [ NCBI taxonomy browser ]Cell source: in-house bred mice (contact: [email protected]) Sex: female [ MGED ]Age: 3 - 4 weeks after birth [ MGED ]Growth conditions: normal
controlled environment20 - 22 oC average temperaturehoused in cages according to German and EU legislationspecified pathogen free conditions (SPF)14 hours light cycle10 hours dark cycle
Developmental stage: stage 28 (juvenile (young) mice) [ GXD "Mouse Anatomical Dictionary" ]Organism part: thymus [ GXD "Mouse Anatomical Dictionary" ]Strain or line: C57BL/6 [International Committee on Standardized Genetic Nomenclature for Mice]Genetic Variation: Inbr (J) 150. Origin: substrains 6 and 10 were separated prior to 1937. This substrain is now probably the most widely used of all inbred strains. Substrain 6 and 10 differ at the H9, Igh2 and Lv loci. Maint. by J,N, Ola. [International Committee on Standardized Genetic Nomenclature for Mice ]Treatment: in vivo [MGED] intraperitoneal injection of Dexamethasone into mice, 10 microgram per 25 g bodyweight of the mouseCompound: drug [MGED] synthetic glucocorticoid Dexamethasone, dissolved in PBS
![Page 28: MGED Ontology: An Ontology of Biomaterial Descriptions for Microarrays](https://reader035.fdocuments.us/reader035/viewer/2022062519/56814f36550346895dbcd303/html5/thumbnails/28.jpg)
MGED Ontology Working Group Goals
1. Identify concepts
2. Collect available controlled vocabularies and ontologies for concepts
3. Define concepts
4. Formalize concept relationships
![Page 29: MGED Ontology: An Ontology of Biomaterial Descriptions for Microarrays](https://reader035.fdocuments.us/reader035/viewer/2022062519/56814f36550346895dbcd303/html5/thumbnails/29.jpg)
MGED Biomaterial Ontology• Under construction
– Using OILed (Not wedded to any one tool)– Generate multiple formats: RDFS, DAML+OIL
• Define classes, provide relations and constraints, identify instances
• Motivated by MIAME and coordinated with MAGE
![Page 30: MGED Ontology: An Ontology of Biomaterial Descriptions for Microarrays](https://reader035.fdocuments.us/reader035/viewer/2022062519/56814f36550346895dbcd303/html5/thumbnails/30.jpg)
MAGE BioMaterial Model
![Page 31: MGED Ontology: An Ontology of Biomaterial Descriptions for Microarrays](https://reader035.fdocuments.us/reader035/viewer/2022062519/56814f36550346895dbcd303/html5/thumbnails/31.jpg)
Building a Microarray Ontology
http://www.cbil.upenn.edu/Ontology/Build_Ontology2.html
![Page 32: MGED Ontology: An Ontology of Biomaterial Descriptions for Microarrays](https://reader035.fdocuments.us/reader035/viewer/2022062519/56814f36550346895dbcd303/html5/thumbnails/32.jpg)
Ontology Available as RDFS
![Page 33: MGED Ontology: An Ontology of Biomaterial Descriptions for Microarrays](https://reader035.fdocuments.us/reader035/viewer/2022062519/56814f36550346895dbcd303/html5/thumbnails/33.jpg)
Ontology in Browseable Form
![Page 34: MGED Ontology: An Ontology of Biomaterial Descriptions for Microarrays](https://reader035.fdocuments.us/reader035/viewer/2022062519/56814f36550346895dbcd303/html5/thumbnails/34.jpg)
Example of Internal Terms
![Page 35: MGED Ontology: An Ontology of Biomaterial Descriptions for Microarrays](https://reader035.fdocuments.us/reader035/viewer/2022062519/56814f36550346895dbcd303/html5/thumbnails/35.jpg)
Example of External Terms
![Page 36: MGED Ontology: An Ontology of Biomaterial Descriptions for Microarrays](https://reader035.fdocuments.us/reader035/viewer/2022062519/56814f36550346895dbcd303/html5/thumbnails/36.jpg)
Example of Combined Internal and External: Treatment
![Page 37: MGED Ontology: An Ontology of Biomaterial Descriptions for Microarrays](https://reader035.fdocuments.us/reader035/viewer/2022062519/56814f36550346895dbcd303/html5/thumbnails/37.jpg)
OWG Use Cases• Return a summary of all experiments that use a specified
type of biosource.– Use “age” to select and order experiments– Use Mouse Anatomical Dictionary Stage 28 to pick experiments
according to “organism part”
• Return a summary of all experiments done examining effects of a specified treatment– E.g., Look for “CompoundBasedTreatment”, “in vivo”– Select “Compound” based on CAS registry number– Order based on “CompoundMeasurement”
• Build gene networks based on biomaterial description– Generate a distance metric based on biosource and use in
calculation of correlation with gene expression level– Generate an error estimation based on biosample (i.e., even when
biosources are identical, there will be variation resulting from different treatments)
![Page 38: MGED Ontology: An Ontology of Biomaterial Descriptions for Microarrays](https://reader035.fdocuments.us/reader035/viewer/2022062519/56814f36550346895dbcd303/html5/thumbnails/38.jpg)
Ontology Working Group Highlights
• First pass ontology of biomaterial descriptions
• Participated in Bio-ontologies Consortium Meeting at ISMB 2001.
• Mail list of about 200 subscribers
![Page 39: MGED Ontology: An Ontology of Biomaterial Descriptions for Microarrays](https://reader035.fdocuments.us/reader035/viewer/2022062519/56814f36550346895dbcd303/html5/thumbnails/39.jpg)
Ontology Working Group Plans
• Finish building biomaterial description ontology
• Expand efforts to include remaining parts of a microarray experiment
• Demonstrate usage to the microarray community
![Page 40: MGED Ontology: An Ontology of Biomaterial Descriptions for Microarrays](https://reader035.fdocuments.us/reader035/viewer/2022062519/56814f36550346895dbcd303/html5/thumbnails/40.jpg)
Acknowledgements
• Past and present members of CBIL for their work on EpoDB and RAD
• The members of the MGED Ontology Working Group for their contributions
• The Bio-Ontologies Consortium for encouragement and guidance
• This presentation is available at http://www.cbil.upenn.edu/Ontology/MGEDOntology1201.ppt