1. From MIAME to MAML: Microarray Gene Expression Database (MGED) Chris Stoeckert Center for Bioinformatics University of Pennsylvania Sept. 19, 2001 GE ^

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 academia, government, and industry from around the world. www.mged.org

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

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 Minimum Information About a Microarray Experiment – MIAME version 1.0 posted Collaboration with OMG on data formats MAML+GEML = MAGE-ML and MAGE-OM MGED 4 meeting in 2001, in Boston in February MGED will become ISCB Special Interest Group

7. MIAME v1.0 Minimum Information About a Microarray Experiment Approved at MGED 3 meeting, Stanford University, March 28, 2001 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: 1.Experimental design: the set of hybridisation experiments as a whole 2.Array design: each array used and each element (spot) on the array 3.Samples: samples used, extract preparation and labeling 4.Hybridisations: procedures and parameters 5.Measurements: images, quantitation, specifications 6.Normalisation controls: types, values, specifications An additional section dealing with the data quality assurance will be added in the next MIAME release.

9. 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 MIAME Section on Sample Source and Treatment

10. MAGE SourceForge

11. MAGE BioMaterial Model

12. MAGE Programming Jamboree Toronto Sept. 2001 Hosted by Jason Goncalves, Iobion APIs, Importers, Exporters Perl, Java, C++

13. MGED OWG home page

14. What is an ontology? An ontology is a specification of concepts that includes the relationships between those concepts. Provides semantics and constraints Allows for computational inferences and reliable comparisons

15. OWG 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

16. Species Resources

18. Concept Definitions

20. 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: norma.howells@itg.fzk.de) Sex: female [ MGED ] Age: 3 - 4 weeks after birth [ MGED ] Growth conditions: normal controlled environment 20 - 22 o C 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 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 mouse Compound: drug [MGED] synthetic glucocorticoid Dexamethasone, dissolved in PBS

21. MGED Biomaterial Ontology Under construction –Using OILed (May use others) –Generating a RDF schema file Motivated by MIAME and coordinated with MAGE Extend classes, provide constraints, provide terms to use

23. MGED Plans MIAME 2.0 –Add/extend sections on normalisation,quality assurance, data analysis MAGE Software –Importers, exporters –Reflect MIAME changes and ontologies Ontologies –Identified resources –Ontology of entire microarray experiment Normalization –Discussion of methods –Common controls User’s Queries –Community needs

24. MGED Summary International grass-roots organization for microarray standards. –Public databases –Published experiments Generated MIAME and MAGE –MIAME: Guidelines for information capture –MAGE: Common object model Building ontologies and normalization standards –Ontologies: Common language –Normalization: New web page MGED 4 in Boston, MA, Feb. 13-16, 2002

25. MGED-Related sites MGED: http://www.mged.org MIAME: http://www.mged.org/Annotations-wg/ MAGE: http://www.geml.org/omg.html http://sourceforge.net/projects/mged/ OWG: http://www.cbil.upenn.edu/Ontology/ NWG: http://www.dnachip.org/mged/normalization.html