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

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. http://www.mged.org

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).

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)

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)

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

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.

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.

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

MAGE SourceForge Update this

MAGE BioMaterial Model

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

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

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

Species Resources

Concept Definitions

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: norma.howells@itg.fzk.de) Sex: female [ MGED ] Age: 3 - 4 weeks after birth [ MGED ] Growth conditions: normal controlled environment 20 - 22 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 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

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

Ontology in Browseable Form

Example of Internal Terms

Example of External Terms

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

Microarray Normalization Standards Check for update

MGED Plans MIAME MAGE Software Ontologies Normalization User’s Queries Annotation tools normalisation,quality assurance, data analysis MAGE Software Importers, exporters Next version in 12 - 18 months Ontologies Extend and apply Ontology of entire microarray experiment Normalization Discussion of methods Common controls User’s Queries Community needs

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

Microarray Ontology