Integrated Corridor Analysis Tool (ICAT) William W. Stoeckert I-95 Corridor Coalition.
Sharing Microarray Experiment Knowledge Chips to Hits Oct. 28, 2002 Chris Stoeckert, Ph.D. Dept. of...
-
Upload
meagan-norton -
Category
Documents
-
view
216 -
download
0
Transcript of Sharing Microarray Experiment Knowledge Chips to Hits Oct. 28, 2002 Chris Stoeckert, Ph.D. Dept. of...
![Page 1: Sharing Microarray Experiment Knowledge Chips to Hits Oct. 28, 2002 Chris Stoeckert, Ph.D. Dept. of Genetics & Center for Bioinformatics University of.](https://reader036.fdocuments.net/reader036/viewer/2022062801/56649e755503460f94b7626e/html5/thumbnails/1.jpg)
Sharing Microarray Experiment Knowledge
Chips to Hits Oct. 28, 2002
Chris Stoeckert, Ph.D.
Dept. of Genetics & Center for Bioinformatics
University of Pennsylvania
![Page 2: Sharing Microarray Experiment Knowledge Chips to Hits Oct. 28, 2002 Chris Stoeckert, Ph.D. Dept. of Genetics & Center for Bioinformatics University of.](https://reader036.fdocuments.net/reader036/viewer/2022062801/56649e755503460f94b7626e/html5/thumbnails/2.jpg)
Nature, October 3, 2002
http://plasmodb.org/David Roos, Jessie Kissinger, Bindu Gajria, Martin Fraunholz, Jules Milgram, Phil
Labo, Amit Bahl, Dave Pearson, Dinesh Gupta, Hagai GinsburgJonathan Crabtree, Jonathan Schug, Brian Brunk, Greg Grant, Trish Whetzel, Matt
Mailman, Li Li
![Page 3: Sharing Microarray Experiment Knowledge Chips to Hits Oct. 28, 2002 Chris Stoeckert, Ph.D. Dept. of Genetics & Center for Bioinformatics University of.](https://reader036.fdocuments.net/reader036/viewer/2022062801/56649e755503460f94b7626e/html5/thumbnails/3.jpg)
![Page 4: Sharing Microarray Experiment Knowledge Chips to Hits Oct. 28, 2002 Chris Stoeckert, Ph.D. Dept. of Genetics & Center for Bioinformatics University of.](https://reader036.fdocuments.net/reader036/viewer/2022062801/56649e755503460f94b7626e/html5/thumbnails/4.jpg)
Desirable Microarray Queries
• Return all experiments using developmental stage X.– Sort by platform type– Which are untreated? Treated?
• Treated by what
• How comparable are these?
• What can these experiments tell me?
![Page 5: Sharing Microarray Experiment Knowledge Chips to Hits Oct. 28, 2002 Chris Stoeckert, Ph.D. Dept. of Genetics & Center for Bioinformatics University of.](https://reader036.fdocuments.net/reader036/viewer/2022062801/56649e755503460f94b7626e/html5/thumbnails/5.jpg)
Microarray Information to be Shared
Figure from:David J. Duggan et al. (1999) Expression Profiling using cDNA microarrays. Nature Genetics 21: 10-14
![Page 6: Sharing Microarray Experiment Knowledge Chips to Hits Oct. 28, 2002 Chris Stoeckert, Ph.D. Dept. of Genetics & Center for Bioinformatics University of.](https://reader036.fdocuments.net/reader036/viewer/2022062801/56649e755503460f94b7626e/html5/thumbnails/6.jpg)
The Computational View of Microarray Information
Need an ontology to unambiguously represent this information.
![Page 7: Sharing Microarray Experiment Knowledge Chips to Hits Oct. 28, 2002 Chris Stoeckert, Ph.D. Dept. of Genetics & Center for Bioinformatics University of.](https://reader036.fdocuments.net/reader036/viewer/2022062801/56649e755503460f94b7626e/html5/thumbnails/7.jpg)
What is an Ontology?• In philosophy, an ontology is a systematic account of
Existence.• In AI, an ontology is a systematic account of what can
be represented.• The knowledge of a domain is represented in a
declarative formalism.– Classes, relations, functions, or other objects are defined
with human-readable text describing what the names mean, and formal axioms that constrain the interpretation.
• A common ontology defines the vocabulary with which queries and assertions are exchanged.
Excerpted and adapted from: http://www-ksl.stanford.edu/kst/what-is-an-ontology.html
![Page 8: Sharing Microarray Experiment Knowledge Chips to Hits Oct. 28, 2002 Chris Stoeckert, Ph.D. Dept. of Genetics & Center for Bioinformatics University of.](https://reader036.fdocuments.net/reader036/viewer/2022062801/56649e755503460f94b7626e/html5/thumbnails/8.jpg)
An Experimental Ontology
• An ontology for microarray experiments– Not an ontology of life but of experiments – Parts are applicable to describing experiments in
general
• Our approach to interfacing with other ontologies is “experimental”– Not mapping terms from related ontologies– Provide a framework to hang other ontologies off of
• Know where to find different types of annotation• How to interpret that annotation
![Page 9: Sharing Microarray Experiment Knowledge Chips to Hits Oct. 28, 2002 Chris Stoeckert, Ph.D. Dept. of Genetics & Center for Bioinformatics University of.](https://reader036.fdocuments.net/reader036/viewer/2022062801/56649e755503460f94b7626e/html5/thumbnails/9.jpg)
http://www.mged.org
![Page 10: Sharing Microarray Experiment Knowledge Chips to Hits Oct. 28, 2002 Chris Stoeckert, Ph.D. Dept. of Genetics & Center for Bioinformatics University of.](https://reader036.fdocuments.net/reader036/viewer/2022062801/56649e755503460f94b7626e/html5/thumbnails/10.jpg)
Relationship of MGED Efforts
MAGEMIAMEDB
MIAMEDBExternal
Ontologies/CVs
MGED Ontology
Software and database developers
Investigators annotating experiments
![Page 11: Sharing Microarray Experiment Knowledge Chips to Hits Oct. 28, 2002 Chris Stoeckert, Ph.D. Dept. of Genetics & Center for Bioinformatics University of.](https://reader036.fdocuments.net/reader036/viewer/2022062801/56649e755503460f94b7626e/html5/thumbnails/11.jpg)
The MGED Ontology Home Page
http://www.cbil.upenn.edu/Ontology
![Page 12: Sharing Microarray Experiment Knowledge Chips to Hits Oct. 28, 2002 Chris Stoeckert, Ph.D. Dept. of Genetics & Center for Bioinformatics University of.](https://reader036.fdocuments.net/reader036/viewer/2022062801/56649e755503460f94b7626e/html5/thumbnails/12.jpg)
The MGED Ontology Home Page
http://mged.sourceforge.net/ontologies/
![Page 13: Sharing Microarray Experiment Knowledge Chips to Hits Oct. 28, 2002 Chris Stoeckert, Ph.D. Dept. of Genetics & Center for Bioinformatics University of.](https://reader036.fdocuments.net/reader036/viewer/2022062801/56649e755503460f94b7626e/html5/thumbnails/13.jpg)
The MGED Ontology Provides a Listing of Resources for Many Species
![Page 14: Sharing Microarray Experiment Knowledge Chips to Hits Oct. 28, 2002 Chris Stoeckert, Ph.D. Dept. of Genetics & Center for Bioinformatics University of.](https://reader036.fdocuments.net/reader036/viewer/2022062801/56649e755503460f94b7626e/html5/thumbnails/14.jpg)
The MGED Ontology Organizes the Resources According to Concepts
![Page 15: Sharing Microarray Experiment Knowledge Chips to Hits Oct. 28, 2002 Chris Stoeckert, Ph.D. Dept. of Genetics & Center for Bioinformatics University of.](https://reader036.fdocuments.net/reader036/viewer/2022062801/56649e755503460f94b7626e/html5/thumbnails/15.jpg)
The MGED Ontology is Structured in DAML+OIL using OILed 3.4
![Page 16: Sharing Microarray Experiment Knowledge Chips to Hits Oct. 28, 2002 Chris Stoeckert, Ph.D. Dept. of Genetics & Center for Bioinformatics University of.](https://reader036.fdocuments.net/reader036/viewer/2022062801/56649e755503460f94b7626e/html5/thumbnails/16.jpg)
MGED Ontology: BiomaterialDescription: BiosourceProperty: Age
![Page 17: Sharing Microarray Experiment Knowledge Chips to Hits Oct. 28, 2002 Chris Stoeckert, Ph.D. Dept. of Genetics & Center for Bioinformatics University of.](https://reader036.fdocuments.net/reader036/viewer/2022062801/56649e755503460f94b7626e/html5/thumbnails/17.jpg)
MGED Ontology: BiosourceOntologyEntry: DiseaseState
![Page 18: Sharing Microarray Experiment Knowledge Chips to Hits Oct. 28, 2002 Chris Stoeckert, Ph.D. Dept. of Genetics & Center for Bioinformatics University of.](https://reader036.fdocuments.net/reader036/viewer/2022062801/56649e755503460f94b7626e/html5/thumbnails/18.jpg)
External References ©-BioMaterialDescription
©-Biosource Property
©-Organism
©-Age
©-DevelopmentStage
©-Sex
©-StrainOrLine
©-BiosourceProvider
©-OrganismPart
©-BioMaterialManipulation
©-EnvironmentalHistory
©-CultureCondition
©-Temperature
©-Humidity
©-Light
©-PathogenTests
©-Water
©-Nutrients
©-Treatment
©-CompoundBasedTreatment
(Compound)
(Treatment_application)
(Measurement)
MGED Ontology Instances
NCBI TaxonomyNCBI Taxonomy
Mouse Anatomical DictionaryMouse Anatomical Dictionary
International Committee on Standardized Genetic Nomenclature for Mice
International Committee on Standardized Genetic Nomenclature for Mice
Mouse Anatomical DictionaryMouse Anatomical Dictionary
ChemIDplusChemIDplus
Mus musculus musculus id: 39442
7 weeks after birth
Stage 28
Female
C57BL/6N
Charles River, Japan
Liver
22 2C
55 5%
12 hours light/dark cycle
Specified pathogen free conditions
ad libitum
MF, Oriental Yeast, Tokyo, Japan
Fenofibrate, CAS 49562-28-9
in vivo, oral gavage
100mg/kg body weight
An example of microarray sample annotation using the MGED ontology Susanna A. Sansone, Helen Parkinson, Philippe Rocca-Serra,
Chris Stoeckert and Alvis Brazma
![Page 19: Sharing Microarray Experiment Knowledge Chips to Hits Oct. 28, 2002 Chris Stoeckert, Ph.D. Dept. of Genetics & Center for Bioinformatics University of.](https://reader036.fdocuments.net/reader036/viewer/2022062801/56649e755503460f94b7626e/html5/thumbnails/19.jpg)
The MGED Ontology in Action: MIAMExpress
![Page 20: Sharing Microarray Experiment Knowledge Chips to Hits Oct. 28, 2002 Chris Stoeckert, Ph.D. Dept. of Genetics & Center for Bioinformatics University of.](https://reader036.fdocuments.net/reader036/viewer/2022062801/56649e755503460f94b7626e/html5/thumbnails/20.jpg)
Journals are Adopting the MGED Standards
Use of Minimal Information About Microarray Experiment (MIAME)
![Page 21: Sharing Microarray Experiment Knowledge Chips to Hits Oct. 28, 2002 Chris Stoeckert, Ph.D. Dept. of Genetics & Center for Bioinformatics University of.](https://reader036.fdocuments.net/reader036/viewer/2022062801/56649e755503460f94b7626e/html5/thumbnails/21.jpg)
The MGED Ontology in Action: RAD
![Page 22: Sharing Microarray Experiment Knowledge Chips to Hits Oct. 28, 2002 Chris Stoeckert, Ph.D. Dept. of Genetics & Center for Bioinformatics University of.](https://reader036.fdocuments.net/reader036/viewer/2022062801/56649e755503460f94b7626e/html5/thumbnails/22.jpg)
![Page 23: Sharing Microarray Experiment Knowledge Chips to Hits Oct. 28, 2002 Chris Stoeckert, Ph.D. Dept. of Genetics & Center for Bioinformatics University of.](https://reader036.fdocuments.net/reader036/viewer/2022062801/56649e755503460f94b7626e/html5/thumbnails/23.jpg)
Generating Forms from the MGED Ontology
OntologyEntry
ExternalDatabases
PHP/SQL WWW
RAD Forms
MGED OntologyAnatomy
DevelopmentalStageDiseaseLineage
PATOAttributePhenotype
Taxon
SRES
RAD3
MGED Ontology
![Page 24: Sharing Microarray Experiment Knowledge Chips to Hits Oct. 28, 2002 Chris Stoeckert, Ph.D. Dept. of Genetics & Center for Bioinformatics University of.](https://reader036.fdocuments.net/reader036/viewer/2022062801/56649e755503460f94b7626e/html5/thumbnails/24.jpg)
Using the MGED standards in RAD• RAD: RNA Abundance Database
– Stoeckert et al.(2000) Bioinformatics
• RAD 3.0– MIAME compliant and MAGE supportive– Building Importers, exporters for MAGE
• Incorporates MGED ontology– Uses OntologyEntry to point to internal tables and
external resources
• Expand processing and analysis information storage– Driven by experience and new approaches
![Page 25: Sharing Microarray Experiment Knowledge Chips to Hits Oct. 28, 2002 Chris Stoeckert, Ph.D. Dept. of Genetics & Center for Bioinformatics University of.](https://reader036.fdocuments.net/reader036/viewer/2022062801/56649e755503460f94b7626e/html5/thumbnails/25.jpg)
ElementAnnotation
Analysis
AnalysisImplementationParam
AnalysisInput
AnalysisImplementation1
0..*1
0..*
1 0..*1 0..*
AnalysisInvocationParamAnalysisInvocation1
0..*1
0..*
1
0..*
1
0..*
1 0..*1 0..*
AnalysisOutput
1
0..*
1
0..*
CompositeElementAnnotation
ArrayAnnotation
CompositeElementImp
0..*0..1 0..*0..1
1
0..*
1
0..*
ElementResultImp CompositeElementResultImp
1
0..*
1
0..*
0..10..* 0..10..*
QuantificationParam
RelatedQuantification
Study
StudyDesignDescription
StudyAssay10..* 10..*
StudyDesignAssay
StudyFactorValueAssayLabeledExtract
BioMaterialImp1
0..*
1
0..*
LabelMethod
0..1
0..*
0..1
0..*
ProtocolParam
MAGEDocumentation
MAGE_ML
0..*
1
0..*
1
AcquisitionParam
Assay
1
0..*
1
0..*
1
0..*
1
0..*
1
0..*
1
0..*
1
0..*
1
0..*
Channel
1
0..*
1
0..*
0..*0..1
0..*0..1
Quantification1
0..*
1
0..*1
0..*
1
0..*
10..*
10..*
1 0..*1 0..*1 0..*1 0..*
Acquisition1
0..*
1
0..*
1
0..*
1
0..*
1
0..*
1
0..*
1
0..*
1
0..*
RelatedAcquisition1 0..*1 0..*1 0..*1 0..*
ProcessImplementationParam
ProcessIO
ProcessInvocation
1
0..*
1
0..*
ProcessInvocationParam10..* 10..*
Array
1
0..*
1
0..*
10..*
10..* 1 0..*1 0..*
BioMaterialMeasurement1 0..*1 0..*
Protocol
1
0..*
1
0..*
1
0..*
1
0..*
0..1
0..*
0..1
0..*
0..1
0..*
0..1
0..*Treatment
1
0..*
1
0..*
1
0..*
1
0..*
0..1
0..*
0..1
0..*
StudyDesign
1
0..*
1
0..*10..* 10..*
1 0..*1 0..*
BioMaterialCharacteristic1
0..*1
0..*
ProcessImplementation10..* 10..*
1
0..*
1
0..*
ElementImp
0..10..* 0..10..*
1
0..*
1
0..*
1
0..*
1
0..*
1
0..*
1
0..*
Control
1
0..*
1
0..*
ProcessResult1 0..*1 0..*
StudyFactor
1
0..*
1
0..*
10..* 10..*
OntologyEntry10..* 10..*
0..*0..1
0..*0..1
1
0..*
1
0..*
RAD schema uses MAGE/MIAMEMAGE
ExperimentArray
BioMaterialBioAssay
BioAssayData Protocol, Descr.
HigherLevelAnalysis
MAGEExperiment
ArrayBioMaterial
BioAssayBioAssayData
Protocol, Descr.HigherLevelAnalysis
MIAMEExperimental Design
Array designSamples
Hybridization, MeasureNormalization
.
MIAMEExperimental Design
Array designSamples
Hybridization, MeasureNormalization
.
![Page 26: Sharing Microarray Experiment Knowledge Chips to Hits Oct. 28, 2002 Chris Stoeckert, Ph.D. Dept. of Genetics & Center for Bioinformatics University of.](https://reader036.fdocuments.net/reader036/viewer/2022062801/56649e755503460f94b7626e/html5/thumbnails/26.jpg)
RAD is now part of GUS-3.0 GUS has 5 name spaces compartmentalizing different
types of information.
Namespace Domain Features
Core Data Provenance Workflows
Sres Shared resorurces Ontologies
DoTSsequence and
annotationCentral dogma
RAD Gene expresssion MIAME/MAGE
TESS Gene regulation Grammars
![Page 27: Sharing Microarray Experiment Knowledge Chips to Hits Oct. 28, 2002 Chris Stoeckert, Ph.D. Dept. of Genetics & Center for Bioinformatics University of.](https://reader036.fdocuments.net/reader036/viewer/2022062801/56649e755503460f94b7626e/html5/thumbnails/27.jpg)
Data Integration
• GO• Species• Tissue• Dev. Stage
Ontologies
SRes
acute myeloid leukemia
Data Provenance
• Ownership• Protection• Algorithms• Similarity• Versioning• Workflow
Core
with sequence similarity to c-fos
GenomicSequence
• Genes, gene models• STSs, repeats, etc• Cross-species analysis
TranscribedSequence
• Characterize transcripts• RH mapping• Library analysis • Cross-species analysis• DOTS
ProteinSequence
• Domains• Function• Structure• Cross-species analysis
DoTS
Transcription factors
•Arrays•SAGE•Conditions
TranscriptExpression
RAD
up-regulated in
• Binding Sites• Patterns• Grammars
Gene Regulation
TESS
and common promoter motifs
![Page 28: Sharing Microarray Experiment Knowledge Chips to Hits Oct. 28, 2002 Chris Stoeckert, Ph.D. Dept. of Genetics & Center for Bioinformatics University of.](https://reader036.fdocuments.net/reader036/viewer/2022062801/56649e755503460f94b7626e/html5/thumbnails/28.jpg)
GUS Supports Multiple ProjectsAllGenesAllGenes PlasmoDBPlasmoDB
EPConDBEPConDB
CoreSRESTESSRADDoTS
Oracle RDBMS Object Layer for Data Loading
Java ServletsOther sites,Other projects,e.g. GeneDB
Other sites,Other projects,e.g. GeneDB
Available at http://www.gusdb.org
![Page 29: Sharing Microarray Experiment Knowledge Chips to Hits Oct. 28, 2002 Chris Stoeckert, Ph.D. Dept. of Genetics & Center for Bioinformatics University of.](https://reader036.fdocuments.net/reader036/viewer/2022062801/56649e755503460f94b7626e/html5/thumbnails/29.jpg)
Summary• The MGED ontology is being developed within the microarray
community to provide consistent terminology for experiments.– Make it easier and more accurate to annotate a microarray experiment. – Use structured fields and controlled terms to query databases.
• This community effort has resulted in a list of multiple resources for many species and a machine-readable document of microarray concepts, definitions, and values.– The MGED Ontology is a work in progress but can be used now to
build forms for databases• RAD has incorporated the MGED ontology for forms
– Can export data from RAD into MAGE– RAD as part of GUS provides integration of gene expression,
annotation, and sequence.
![Page 30: Sharing Microarray Experiment Knowledge Chips to Hits Oct. 28, 2002 Chris Stoeckert, Ph.D. Dept. of Genetics & Center for Bioinformatics University of.](https://reader036.fdocuments.net/reader036/viewer/2022062801/56649e755503460f94b7626e/html5/thumbnails/30.jpg)
Acknowledgements
• MGED Ontology– Helen Parkinson (EBI)
– Trish Whetzel
– The MGED Ontology Working Group
– MAGE working group
• RAD/GUS– Brian Brunk– Jonathan Crabtree– Steve Fischer– Yongchang Gan– Greg Grant – Hongxian He– Li Li– Junmin Liu – Matt Mailman– Elizabetta Manduchi– Joan Mazzarelli– Shannon McWeeney (OHSU) – Debbie Pinney– Angel Pizarro– Jonathan Schug– Trish Whetzel
www.mged.org www.cbil.upenn.edu
![Page 31: Sharing Microarray Experiment Knowledge Chips to Hits Oct. 28, 2002 Chris Stoeckert, Ph.D. Dept. of Genetics & Center for Bioinformatics University of.](https://reader036.fdocuments.net/reader036/viewer/2022062801/56649e755503460f94b7626e/html5/thumbnails/31.jpg)
http://www.ebi.ac.uk/SOFG