Post on 28-Dec-2015
transcript
Susanna-Assunta Sansone
(Toxicogenomics project coordinator)
Microarray Informatics Team
EMBL- EBI (European Bioinformatics Institute)
Transcriptome Symposium, April 2002
CHU Pitié-Salpêtrière, Université Paris VI
MIAME and ArrayExpress – a standard for microarray
gene expression data and the public database at EBI
EMBL- EBI centre for research and services in bioinformatics that makes and maintains public db:
• EMBL Nucleotide Sequence, SWISS-PROT, Ensembl, MSD, etc.
Practical reasons:• Easy data access• Resolves local storage issues• Common data exchange formats can be developed
Scientific reasons:• Curation can be applied• Annotation can be controlled • Additional info can be stored that is missing in publications• Improve data comparison !
Public standard can be applied
Why have a public database?
MIAME standard
MIAME annotation challenge:• MGED BioMaterial Ontology
Uses of MIAME concepts:• ArrayExpress:
a public repository for gene expression data
• MIAMExpress
submission and annotation tool
Talk structure
Standard for microarray data - Why?
Size of dataset Different platforms - nylon, glass
Different technologies - oligos, spotted
References to external db not stable! Array annotation Sample annotation Data sharing needs standardized way to
annotate and record the information!
Microarray Gene Expression Data Group: EBI + world’s largest microarray labs and companies
(Sanger, Stanford, TIGR, Universite D'Aix-Marseille II,
Affymetrics, Agilent, NCBI, DDBJ, etc.)
MGED Group aims to• Facilitate adoption of standards for:
– Experiment annotation– Data representation
• Introduce standard for:– Experimental controls– Data normalization methods
Standard for microarray data - MGED Group
Minimum information about a microarray experiment
NOT a formal specification BUT a set of guidelines
Sufficient information must be recorded to:• Correctly interpret and verify the results• Replicate the experiments
Structured information must be recorded to:• Query and correctly retrieve the data• Analyse the data
MIAME- Brazma et al., Nature Genetics, 2001
General MIAME principles
ArraySample
• Sample source• Sample treatments• Extraction protocol• Labeling protocol
• Array design information• Location of each element• Description of each element
Hybridization protocol
• Quantification matrix• Analysis protocol• Software specifications
• Image• Scanning protocol• Software specifications
Hybridisation
MIAME 6 parts of a microarray experiment
MIAME
MIAME
• Strategy• Algorithm• Control array elements
Final data
Normalisation
• 3 data processing levels• Lack of gene expression measurement units !
ArraySample HybridisationArraySample Hybridisation
ArraySample HybridisationArraySample Hybridisation
Experiment
MIAME 6 parts of a microarray experiment
Annotation implementations are required !• Avoid/reduce free text descriptions• Use of controlled terms• Definitions and sources for each term• Remove of synonyms, or use of synonym mappings• Data curation at source (LIMS)• Integration of controlled terms in query interfaces
Facilitate data queries-analysis…….
MIAME – Annotation challenge
Samples
Gene expression matrix
A gene expression database from the data analyst’s point of view
Gene expression levels?Gen
es
and
tran
scrip
tion
units
Samples
Gen
es
and
tran
scrip
tion
units
Gene expression matrix
A gene expression database from the data analyst’s point of view
• Array description:- Gene annotations
• Sample annotations:- Source- Treatment
Gene expression levels
MIAME - Gene annotation
Unambiguous identification
Synonyms !• Community approved names• Alternative to gene names
Usable external sources e.g.:• EMBL-GenBank - sequence accession n.• Jackson Lab - approved mouse gene names• HUGO - approved human gene names• GO categories - function, process, location
MIAME - Sample annotation Gene expression data only have a meaning in the context of detailed sample descriptions !
Usable external sources e.g.:• NCBI Taxonomy - organisms• Jackson Lab - mouse strains names
• Mouse Anatomical Dictionary – mouse anatomy
• ChemID – compounds• ICD-9 – diseases classification
More is needed…..
Annotation – implementations required!
Need an ontology to describe the sample:• Defining controlled vocabularies and……• ….Using existing external ontologies
Integrate the ontology in LIMS and databases:• Develop browser or interface for the ontology• Develop internal editing tools for the ontology
However some free text description is
unavoidable
What CV and ontology are?
Controlled Vocabulary (CV):• Set of restrictive terms used to describe
something, in the simplest case it could be a list
Ontology is more then a CV:• Describes the relationship between the terms in
a structured way, provides semantics and constraints
• Capture knowledge and make it machine processable
Sample annotation – MGED BioMaterial Ontology
Under construction by Chris Stoeckert (Univ. of Penn.) and MGED members
Use OILed (rdf, daml and html files available) Motivated by MIAME and guided by ‘case scenarios’ Defines terms, provides constraints, develops CVs for
sample annotation Links also to external CVs and ontologies Will be extended to other part of a microarray
experiment that need to be described
Sample annotation – MGED BioMaterial Ontology
an example
Sample source and treatment description, and its correct annotation using the MGED BioMaterial Ontology
classes and correspondent external references:
“Seven week old C57BL/6N mice
were treated with fenofibrate.
Liver was dissected out, RNA prepared………”
©-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 BioMaterial Ontology Instances
7 weeks after birth
Female
Charles River, Japan
22 2C
55 5%
12 hours light/dark cycle
Specified pathogen free conditions
ad libitum
MF, Oriental Yeast, Tokyo, Japan
in vivo, oral gavage
100mg/kg body weight
External References
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
Stage 28
C57BL/6
Liver
Fenofibrate, CAS 49562-28-9
MIAME standard
Sample annotation:• MGED BioMaterial Ontology
Talk structure
Uses of MIAME concepts:• ArrayExpress a
public repository for gene expression data
• MIAMEpresssubmission and annotation tool
Specifies the content of the information:• Sufficient• Structured
Uses of MIAME concepts
Uses:• Creation of MIAME-compliant LIMS or databases e.g: ArrayExpress
• Development of submission/annotation tool for generating MIAME-compliant information e.g.: MIAMExpress
Users
EBIWeb server
Browse-Query
Central database
Data warehouse
ArrayExpress
Curationdatabase
Image server
Update
MAGE-ML
OutputLoader
MIAMExpress
Submission
LIMS
Submission
MIAMExpress
ArrayExpress – data flow
Central database
Data warehouse
ArrayExpress
Implementation in ORACLE of the MAGE-OM model:• Microarray gene expression - Object Model• OMG approved standard (MGED and Rosetta, 2001)• Model developed in UML
Object model-based query mechanism:• Automatic mapping to SQL
Independent of:• Experimental platform• Image analysis method• Normalization method
MAGE-ML data loader:• Microarray gene expression - Mark-up Language generated from model
ArrayExpress - details
Final data
Normalisation
ArraySample HybridisationArraySample Hybridisation
ArraySample HybridisationArraySample Hybridisation
Experiment
MIAME 6 parts of a microarray experiment
ArrayExpress – conceptual model
ArrayExpress – simplified model
• Classes are represented by boxes
• Classes describe objects
• Related classes are grouped together in packages
• MAGE-OM has 16 packages, ~ 150 tables
• Human data - EMBL (ironchip)
• Yeast data - EMBL• S. pombe - Sanger Institute • Available as example
annotated and curated data sets
• Array descriptions - TIGR• Array description - Affymetrix• Mouse data - TIGR and HGMP• Anopheles data - EMBL• Direct pipeline - Sanger Institute
LIMS• Data - DESPRAD partners• Toxicogenomics data- ILSI HESI
Near future:Currently:
ArrayExpress -data (via MAGE-ML)
SEQLOGO
EPCLUST Expression data GENOMES
sequence, function, annotation
SPEXSdiscover patterns
URLMAPprovide links
External data, toolspathways, function,
etc.
PATMATCHvisualise patterns
EP:GOGeneOntology
EP:PPIProt-Prot ia.
ArrayExpress – link to Expression Profiler
Expression data
User support and help documentation:• Ontologies and CV’s• Minimize free text, removal of synonyms• Help on MAGE-ML format and MAGE-OM
MIAME compliance-check
Curation at source (LIMS)
To provide high-quality, well-annotated data
and allow automated data analysis
ArrayExpress – curation effort
MIAMExpress
Submission and annotation tool:• Curators will monitor the submissions
Based on MIAME concepts:• Experiment, Array and Protocol submissions • Generates MIAME-compliant information
Uses MGED BioMaterial Ontology terms:• Terms and required fields are explained
Allows user driven ontology development:• User can provide new terms and their sources
Allows browsing:• Array descriptions• Protocols
MIAMExpress - details
MIAMExpress
Version 1 launch in December 2002 Expected users:
• Limited local bioinformatic support• No LIMS on site• Small scale users with custom made arrays
Can be installed as local version:• As a lab-book to annotate your experiment • As part of a LIMS
Interfaces:• Version 1 is general• Future versions, application specific interfaces
- Species specific- Toxicogenomics specific (ILSI- HESI)
MIAMExpress - details
Load public data into ArrayExpress:• TIGR, EMBL, ILSI HESI, DESPRAD partners
Improve query interfaces
Launch MIAMExpress v.1 (Dec.2002)
MIAMExpress v.2:• Extended according to the user needs• Integrated MGED ontology• Increased usability, flexibility and scalability
Develop curation tools
ArrayExpress - future
Acknowledgments Microarray Informatics Team at EBI (19 members):
• Alvis Brazma (Team Leader and MGED President)
• Helen Parkinson (Curation Coordinator)
• Mohammad Shojatalab (MIAMExpress Database Programmer)
• Ugis Sarkans (ArrayExpress Database development coordinator)
• Jaak Vilo (Expression Profiler)
• Curators and Programmers.
MGED members and working groups:• Alvis Brazma (MGED President, MIAME)
• Chris Stoeckert, U. Penn. (MGED Ontology Working Group)
Open sources resources:• ArrayExpress and MIAMExpress schema-access to code• MIAME document and glossary• MAGE-ML dtd and annotation examples• MGED Ontology and other resources………
www.mged.org / www.ebi.ac.uk/microarraysansone@ebi.ac.uk
Be aware of MIAME !• Nature, Lancet and have already expressed their interest• Founding agencies
Join MGED meetings, tutorials and mailing lists:• MGED-5 meeting in Japan (Sept. 2002)• Ontology for BioSample description, EBI (Nov. 2002)
Resources and ….messages