1. From MIAME to MAML: Microarray Gene Expression Database (MGED)^
From MIAME to MAML: Microarray Gene Expression Database (MGED)
Chris Stoeckert
Center for Bioinformatics
University of Pennsylvania
Nov. 12, 2001

2. 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.

3. Why Microarray Data Standards?
Standards are needed for:
Evaluating microarray data (standards in quality measures, protocols).
Analysing microarray data (standards in annotations, data provided)
Exchanging microarray data (standards in data exchange).

4. How to Create Microarray Data Standards
Understand thoroughly what is the minimum information about a microarray experiment that is needed to interpret it unambiguously and what is the structure of this information (objects and relationships)
Create the technical data format able to capture this information
Find or generate appropriate controlled vocabularies and ontologies
Create standards in experiments themselves (standard controls and protocols)

5. MGED Working Groups
Experiment description and data representation standards (Alvis Brazma, EMBL-EBI)
Microarray data XML exchange format (Paul Spellman, UC Berkeley)
Ontologies for sample description (Chris Stoeckert, U Penn)
Normalisation, quality control and cross-platform comparison (Frank Holstege, UMC Utrecht, Roger Bumgarner, U Wash)

6. MGED Milestones
MGED 2 meeting in Heidelberg in 2000, MGED 3 in Stanford in 2001, both ~ 300 participants
MGED 4 meeting February 2002, in Boston (satellite to AAAS meeting)
MGED will become ISCB Special Interest Group
Minimum Information About a Microarray Experiment – MIAME version 1.0 posted
Nature Genetics in press
Participation with OMG on data formats MAML+GEML = MAGE-ML and MAGE-OM

7. MIAME v1.0
Minimum Information About a Microarray Experiment Approved at MGED 3 meeting, Stanford University, March 28,
The goal of the MIAME is to specify the minimum information that must be reported about an array based gene expression monitoring experiment in order to ensure the interpretability of the results, as well as potential verification by third parties. This is to facilitate establishing repositories and a data exchange format for array based gene expression data. The MGED group will encourage scientific journals and funding agencies to adopt policies requiring data submissions to repositories, once MIAME compliant repositories and annotation tools are established.

8. MIAME Descriptions Definition:
The minimum information about a published microarray-based
gene expression experiment should include a description of the:
Experimental design: the set of hybridisation experiments as a whole
Array design: each array used and each element (spot) on the array
Samples: samples used, extract preparation and labeling
Hybridisations: procedures and parameters
Measurements: images, quantitation, specifications
Normalisation controls: types, values, specifications
An additional section dealing with the data quality assurance
will be added in the next MIAME release.

9. MIAME Section on Sample Source and Treatment
sample source and treatment ID as used in section 1
organism (NCBI taxonomy)
additional "qualifier, value, source" list; the list includes:
cell source and type (if derived from primary sources (s))
sex
age
growth conditions
development stage
organism part (tissue)
animal/plant strain or line
genetic variation (e.g., gene knockout, transgenic variation)
individual
individual genetic characteristics (e.g., disease alleles, polymorphisms)
disease state or normal
target cell type
cell 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)
compound
is additional clinical information available (link)
separation technique (e.g., none, trimming, microdissection, FACS)
laboratory protocol for sample treatment

10. MAGE SourceForge
Update this

11. MAGE BioMaterial Model

12. MAGE Programming Jamboree
Toronto Sept. 2001
Hosted by Jason Goncalves, Iobion
Held remotely
APIs, Importers, Exporters
Perl, Java, C++
Jamoboree 2 at EBI in December 2001

13. 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

14. Ontology Working Group Use Cases
Return a summary of all experiments that use a specified type of biosource.
Group the experiments according to treatment.
Return a summary of all experiments done examining effects of a specified treatment
Group the experiments according to biosource.
Return a summary of all experiments measuring the expression of a specified gene.
Indicate when experiments confirm results, provide new information, or conflict.
Generate a distance metric for experiment types
Generate an error estimation for experimental descriptions

15. Species
Resources

16. Concept
Definitions

17. Excerpts from a Sample Description courtesy of M. Hoffman, S
Excerpts from a Sample Description courtesy of M. Hoffman, S. Schmidtke, Lion BioSciences
Organism: mus musculus [ NCBI taxonomy browser ]
Cell source: in-house bred mice (contact:
Sex: female [ MGED ]
Age: weeks after birth [ MGED ]
Growth conditions: normal
controlled environment
oC average temperature
housed in cages according to German and EU legislation
specified pathogen free conditions (SPF)
14 hours light cycle
10 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 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 mouse
Compound: drug [MGED] synthetic glucocorticoid Dexamethasone, dissolved in PBS

18. MGED Biomaterial Ontology
Under construction
Using OILed (May use others)
Generate multiple formats: RDFS, DAML+OIL
Motivated by MIAME and coordinated with MAGE
Extend classes, provide constraints, provide terms to use

19. Ontology in Browseable Form

20. Example of Internal Terms

21. Example of External Terms

22. Relationship of MGED Efforts
MIAME DB
MAGE
MGED Ontology
MIAME DB
External
Ontologies/CVs

23. Microarray Normalization Standards
Check for update

24. MGED Plans MIAME MAGE Software Ontologies Normalization User’s Queries
Annotation tools
normalisation,quality assurance, data analysis
MAGE Software
Importers, exporters
Next version in months
Ontologies
Extend and apply
Ontology of entire microarray experiment
Normalization
Discussion of methods
Common controls
User’s Queries
Community needs

25. MGED-Related sites MGED: http://www.mged.org
MIAME:
MAGE:
OWG:
NWG:

26. Microarray Ontology