The MGED Ontology:A framework for describing

functional genomics experiments

SOFG Nov. 19, 2002

Chris Stoeckert, Ph.D.

Dept. of Genetics & Center for Bioinformatics

University of Pennsylvania

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

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?

Microarray Information to be Shared

Figure from:David J. Duggan et al. (1999) Expression Profiling using cDNA microarrays. Nature Genetics 21: 10-14

The Computational View of Microarray Information

Need an ontology to unambiguously represent this information.

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

http://www.mged.org

Relationship of MGED Efforts

MAGEMIAMEDB

MIAMEDBExternal

Ontologies/CVs

MGED Ontology

Software and database developers

Investigators annotating experiments

The MGED Ontology Home Page

http://mged.sourceforge.net/ontologies/

The MGED Ontology Provides a Listing of Resources for Many Species

The MGED Ontology Organizes the Resources According to Concepts

The MGED Ontology is Structured in DAML+OIL using OILed 3.4

MGED Ontology: BiomaterialDescription: BiosourceProperty: Age

MGED Ontology: BiosourceOntologyEntry: DiseaseState

ArrayExpress

MIAMExpress

RADMAGE-ML data exchange

Ontology instances propagated to submission/annotation web forms

Curation of user defined terms, before inclusion in the ontology

User defined terms collected via forms

MGED Ontology

BiomaterialDescription

SexC

C

C

C Gender

documentation: Subclass of sex applicable to heterogametic species (i.e., those in which the sexes produce gametes of markedly different size). Males produce small numerous gametes. Females produce small numbers of large gametes. Hermaphrodites are individuals with both male and female characteristics. Mixed refers to a population of individuals with more than one type of gender.

used in individuals: female, hermaphrodite,male,mixed_sex,unknown_sex

The MGED Ontology in Action: MIAMExpress

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

.

The MGED Ontology in Action: RAD

• Add screen shot of study factor

RAD Generic Form for BioMaterial Characteristics

RAD Project-Specific Form - PlasmoDB

Acquiring New Terms

Add term from SRes

Add term from an External Database

OR

Generating Forms from the MGED Ontology

OntologyEntry

ExternalDatabases

PHP/SQL WWW

RAD Forms

MGED OntologyAnatomy

DevelopmentalStageDiseaseLineage

PATOAttributePhenotype

Taxon

SRES

RAD3

MGED Ontology

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 resources Ontologies

DoTSsequence and

annotationCentral dogma

RAD Gene expresssion MIAME/MAGE

TESS Gene regulation Grammars

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

http://www.gusdb.org

Acknowledgements

• MGED Ontology– Helen Parkinson (EBI)

– Trish Whetzel

– The MGED Ontology Working Group

– MAGE working group

– Angel Pizarro

– Nelson Axelrod

• 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