1. OncoTrack Bioinformatics Workshop Max Planck Institute for Molecular Genetics, Berlin Wednesday 6 th November 2013 TimeSubject 13:30-15:00 Introduction to Enzymes and the Enzyme portal Tutorial exercises 15:00-15:30Tea & Coffee break 15:30-16:30Introduction to Enzymes and the Enzyme portal (cont.) Tutorial exercises 16:30-17:00 Discussions and Feedback

2. Cheminformatics and Metabolism Team The EBI Enzyme Portal

3. Problem Case Diabetes  Insulin  Insulin enzyme “Look for an enzyme that acts as a receptor to “insulin”, understand how its Deficiency relates to “Diabetes Mellitus, Type 2, and explore more on its enzymatic reaction and pathways”.

4. Solution ? MACiE

5. Enzyme-related resources at EBI MACiE

6. Enzyme-related resources at EBI Protein Data Bank in Europe Protein structure Provides access to Biological macromolecular structure data Database of biomedical research literatures Europe PMC

7. Enzyme-related resources at EBI Chemical Entities with Biological Interest Freely available repository of molecular entities. Main focus is on small chemical compounds Database of bioactive drug-like small molecules Contains calculated properties and abstracted bioactivities.

8. Enzyme-related resources at EBI MACiE Curated pathway database Manually annotated database of chemical reactions Mechanism, Annotation and Classification in Enzymes database of catalytic metal ions

9. Enzyme-related resources at EBI Universal Protein Resource catalog of information on proteins Integrated relational Enzyme database enzyme nomenclature

10. Enzyme-related resources at EBI MACiE

11. Enzyme-related resources at EBI MACiE

12. Enzyme-related resources at EBI MACiE

13. Enzyme-related resources at EBI MACiE Enzyme Portal

14. Enzyme-related resources at EBI MACiE Enzyme Portal

15. Enzyme-related resources at EBI MACiE Enzyme Portal

16. Stakeholders' Requirements  Data source to be acknowledged  Free and open access to the data  Scope: Enzyme related resources

17. User Requirements - Functionalities Search Free text Protein sequence Chemical structure Browse EC classification Expression Taxonomy Disease Chemical compound Compare enzymes Customized downloads

18. User Requirements - Content  Enzyme Headline  Pathway  Reaction  Structure-Function  Diseases and Drugs  References

19. Searching The initial query is resolved into UniProt accessions: Keyword search: Uses EBI search web service Protein sequence search: Uses NCBI-BLAST web service UniProt accessions are filtered for enzymes and grouped as orthologs. A summary is built for every ortholog group using UniProt and IntEnz web services. Search results include ‘tags’ for related species, chemical compounds and diseases, which allow their filtering.

20. Enzyme data Retrieved on demand from the source: Enzyme highlight  IntEnz and UniProt WS Structure  PDBe WS (DAS) Reactions and pathways  Rhea and Reactome WS Small molecules  UniProt, ChEMBL, IntEnz, ChEBI WS Disease  UniProt and BioPortal WS (EFO, OMIM, MeSH) Literature  Europe PubMed Central, UniProt and PDBe WS

21. No releases, no curation Data is retrieved fresh from the source on demand. Only a minimal map of cross-references is kept in a database in order to speed up the building of search filters. The map is rebuilt immediately after every UniProt release.

22. Enzyme portal cross-references

23. Enzyme Portal home page

24. Enzyme Portal Results Page

29. Enzyme Portal Entry Summary

30. Enzyme Portal Protein Structure

31. Enzyme Portal Reactions/Pathways

33. Enzyme Portal Small Molecules

36. Enzyme Portal Diseases

37. Enzyme Portal Literature

38. Enzyme Portal Advanced Search

40. Enzyme Portal Advanced Result

41.  Search by sequence or chemical structure  Browsing  Enzyme comparison  Customised downloads Next Release date : January 2014 Enzyme Portal – Work in Progress

42. Acknowledgements  Data providers  Testers  User Experience Analysts  Everyone who has contributed to the Enzyme Portal  You Paula de MatosRafael Alcántara http://www.ebi.ac.uk/enzymeportal Christoph SteinbeckJoseph Onwubiko Jenny Cham

43. Time for exercises……. http://www.ebi.ac.uk/enzymeportal/