1. MIAMExpress and the development of annotation ontologies for gene expression experiments Ele Holloway Microarray Informatics European Bioinformatics Institute Microarrays and Data Mining 10 th -11 th December 2002

2. Outline  Capturing information  Ontologies  MIAMExpress

3. Capturing information  Lab book – only useful for the individual  Annotate in a controlled way  Submit information to a database / LIMS Need information understandable by all Allows easy retrieval Available to other researchers

4. What is an ontology?  A kind of controlled vocabulary (CV) expressed in a structured way.

5. Components of an ontology  Class  Instance Has a definition and a relationship to other classes (is-a, part-of, kind-of). Terms that are contained within a class. = container for information. e.g. An exon is part of a gene

6. An ontology – what can it do?  Captures knowledge  Shared understanding  Structure enriches CV  Computer ‘readable’

7. Why do we need an ontology for the database?  To help users annotate their data usefully and easily  To perform structured queries  To accurately compare data  To avoid problems with free text searching  To avoid excessive curation workload in future

8. Annotation Data mining Controlled vocabulary Free text Database Natural language processing

9. Standards and Ontologies for Functional Genomics Aim: To bring together scientists (biologists and bioinformaticians) developing standards and ontologies 17 – 20 th November 2002 Hinxton http://www.ebi.ac.uk/SOFG

10. Examples of ontologies and CVs  MGED Ontology – For describing samples used in microarray experiments – Gene Ontology – Edinburgh Mouse Atlas Project – Drosophila genome database  NCBI Taxonomy  GO  EMAP  FlyBase - All organisms represented in the genetic databases

11. Infrastructure EBI Expression Profiler External bioinformatics databases www Submissions Queries www Data analysis www MAGE-ML Local MIAMExpress installations Array manufacturers LIMS Data pipelines ArrayExpress (Oracle) Other microarray databases Data analysis software Microarray software MAGE-ML import/export MIAMExpress MAGE-ML

12. MIAME requirements  Experimental design  Array design  Samples  Measurements  Normalization controls  Hybridizations Nature Genetics 29(4): 365-371

13. External links NormalizationData ArrayHybridizationSample Experiment 6 parts of a microarray experiment MEDLINE Publication details MGED Experiment details NCBI taxonomy CAS/ Merck EMAP Mouse stage Species Chemical compd. EMBL Gene acc. n o. Gene name GO Genew

14. MGED Ontology  Community effort  Supports efforts of MAGE - MGED Society  Describes the parts of a microarray experiment  References out to external ontologies

16. MGED Ontology  Structured in DAML+OIL using OilEd 3.4

18. MIAMExpress  Submission and annotation tool  Based on MIAME concepts  Array, Experiment and Protocol submissions  Perl-CGI, MySQL database

19. Submission process

20. http://www.ebi.ac.uk/miamexpress Tour of MIAMExpress  Login +Password  Multi-user environment  Control over data access

24. Login New/Pending Experiment Sample 1Sample 2Sample 3Sample 4

26. Login New/Pending Experiment Sample 1Sample 2Sample 3Sample 4 Extracts 1….n E1E1 E1E1 E1E1 E1E1 E2E2 E2E2 E2E2 E2E2 EnEn EnEn EnEn EnEn

27. Login New/Pending Experiment Sample 1Sample 2Sample 3Sample 4 Extracts 1….n E1E1 E1E1 E1E1 E1E1 E2E2 E2E2 E2E2 E2E2 EnEn EnEn EnEn EnEn LE Lab. Extr. 1….n

29. Login New/Pending Experiment Sample 1Sample 2Sample 3Sample 4 Extracts 1….n E1E1 E1E1 E1E1 E1E1 E2E2 E2E2 E2E2 E2E2 EnEn EnEn EnEn EnEn LE Lab. Extr. 1….n Hybridizations Array 1 Array 2 Array 3 Array n Data 1 Data 2 Data 3 Data n

33. Submission successful  Curation  Export of MAGE-ML  Loading to ArrayExpress

34. ArrayExpress MIAMExpress RAD MAGE-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 Sex C 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

35. Resources  Microarray Informatics Group http://www.ebi.ac.uk/microarray/  MIAMExpress http://www.ebi.ac.uk/miamexpress/  MGED Ontology Working Group http://mged.sourceforge.net/ontologies/  Sourceforge  http://sourceforge.net/ http://sourceforge.net/

36. Acknowledgements ArrayExpress  Ugis Sarkans  Gonzalo Garcia  Ahmet Oezcimen  Anjan Sharma Curation  Helen Parkinson  Gaurab Mukherjee  Philippe Rocca-Serra  Susanna Sansone MIAMExpress  Mohammad Shojatalab  Niran Abeygunawardena  Sergio Contrino Alvis Brazma MGED Ontology  Chris Stoeckert (U. Penn)

37.  GO http://www.geneontology.org  EMAP http://genex.hgu.mrc.ac.uk/  FlyBase http://flybase.bio.indiana.edu/  NCBI Taxonomy http://www.ncbi.nlm.nih.gov/Taxonomy/taxonomyhome.html/