1. Introduction to metabolism: Compounds, Reactions, Enzymes and Pathways Kristian Axelsen, Alan Bridge Elisabeth Coudert & Anne Morgat SIB Swiss Institute of Bioinformatics Swiss-Prot, Geneva StarOmics course Nov. 19-23

2. 2, StarOmics course,Lausanne, Monday November 19 th http://education.expasy.org/cours/StarOmics2012/

3. 3, StarOmics course,Lausanne, Monday November 19 th 3 Metabolism of living organisms can be apprehended as a network of biochemical reactions, connected by the chemical compounds involved in these reactions and generally catalyzed by enzymes.

4. 4, StarOmics course,Lausanne, Monday November 19 th Thymidine kinase is a phosphotransferase. It catalyzes the reversible phosphorylation of thymidine (2'-deoxythymidine) to dTMP ( 2'-deoxythymidine monophosphate) using ATP as phosphoryl donor. 4

5. 5, StarOmics course,Lausanne, Monday November 19 th Enzyme nomenclature 5 By the late 1950's it had become evident that the nomenclature of enzymology, in the absence of any guiding authority, in a period when the number of known enzymes was increasing rapidly, was getting out of hand. The General Assembly of the International Union of Biochemistry (IUB) decided, during the third International Congress of Biochemistry in Brussels in August, 1955, to set up an International Commission on Enzymes. This step was taken in consultation with the International Union of Pure and Applied Chemistry (IUPAC). The International Commission on Enzymes was established in 1956

6. 6, StarOmics course,Lausanne, Monday November 19 th Enzyme nomenclature The Nomenclature Committee of the IUBMB (International Union of Biochemistry and Molecular Biology) is trying to categorise all known enzymes and to formalise their nomenclature. 6 http://www.chem.qmul.ac.uk/iubmb/

7. 7, StarOmics course,Lausanne, Monday November 19 th 1= Oxidoreductases 2= Transferases 3= Hydrolases 4= Lyases 5= Isomerases 6= Ligases The 1st digit = Enzyme class Depends on the type of the catalyzed reaction The 2nd digit = Subclass Defined by the reaction mechanism The 3rd digit = Subsubclass Indicates the nature of the molecules involved The 4th digit = Serial number Transferase Transferring phosphorous-containing groups Phosphotransferases with an alcohol group as acceptor Thymidine kinase. Enzyme Commission number (EC number) EC 1.2.3.4 7

8. 8, StarOmics course,Lausanne, Monday November 19 th NC-IUBMB – enzyme nomenclature The International Commission on Enzymes was established in 1956 Composed of 10 members; enzymologists and chemists (also 10 members today) Today members are also from databases: Brenda (Ida and Dietmar Schomburg), KEGG (Masaaki Kotera), MetaCyc (Ron Caspi), and SIB (Kristian Axelsen) First printed version of the EC list 1961 (712 entries) ENZYME db: First computer readable version of the EC list, April 1990 8 Historical Introduction: http://www.chem.qmul.ac.uk/iubmb/enzyme/history.html

9. 9, StarOmics course,Lausanne, Monday November 19 th Development of ENZYME nomenclature

10. 10, StarOmics course,Lausanne, Monday November 19 th StarOmics training agenda Chemicals Reactions Enzymes Pathways

11. 11, StarOmics course,Lausanne, Monday November 19 th Metabolic resources Chemicals Reactions Enzymes / Transporters Pathways StarOmics training agenda

12. 12, StarOmics course,Lausanne, Monday November 19 th Major metabolic resources used during this training BioCyc / MetaCyc KEGG SIB / EBI biocuration effort Gene Ontology Swiss project: SystemX.ch / MetaNetX European project: Microme

13. 13, StarOmics course,Lausanne, Monday November 19 th 14 octobre 2008UJF Grenoble http://biocyc.org

14. 14, StarOmics course,Lausanne, Monday November 19 th MetaCyc (http://metacyc.org/) is a database of manually curated non-redundant metabolic pathways supported by experimental evidence. MetaCyc stores pathways involved in primary and secondary metabolism. This includes chemical compounds, reactions, proteins, protein complexes, and genes associated to these pathways Stats of MetaCyc V16.1 MetaCyc

15. 15, StarOmics course,Lausanne, Monday November 19 th 14 octobre 2008UJF Grenoble http://www.genome.jp/kegg/ KEGG: Kyoto Encyclopedia of Genes and Genomes KEGG is an integrated database resource for the computational representation of biological systems from the integration of genomic and chemical information into molecular wiring diagrams of interaction, reaction and relation networks (systems information)

16. 16, StarOmics course,Lausanne, Monday November 19 th GENES (genomic information) LIGAND (chemical information) PATHWAY/BRITE (System information) KO

17. 17, StarOmics course,Lausanne, Monday November 19 th SIB & EBI biocuration effort genes and genomes complexes chemicals 17 towards sytems biology…

18. 18, StarOmics course,Lausanne, Monday November 19 th UniProt: the Universal Protein resource Since 2002 a merger and collaboration of three databases: The mission of UniProt is to provide the scientific community with a comprehensive, high-quality and freely accessible resource of protein sequence and functional information.

19. 19, StarOmics course,Lausanne, Monday November 19 th http://www.uniprot.org/ UniProt is updated and distributed every 4 weeks It can be accessed online for searches or download at

20. 20, StarOmics course,Lausanne, Monday November 19 th To support biological research by providing a freely accessible, stable, comprehensive, fully classified, richly and accurately annotated protein sequence knowledgebase, with extensive cross-references and querying interfaces. UniProt is comprised of four major components UniProt mission

21. 21, StarOmics course,Lausanne, Monday November 19 th UniProt database growth

22. 22, StarOmics course,Lausanne, Monday November 19 th http://www.geneontology.org

23. 23, StarOmics course,Lausanne, Monday November 19 th http://www.ebi.ac.uk/GOA/

24. 24, StarOmics course,Lausanne, Monday November 19 th 3 categories of GO terms

25. 25, StarOmics course,Lausanne, Monday November 19 th http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0009507&session_id=9452amigo1349170795

26. 26, StarOmics course,Lausanne, Monday November 19 th ~ 35’000 GO terms ~12’000’000 gene products are linked to GO terms: but how ? >96% of all annotations are inferred without direct manual curation ! Orthology, Paralogy and Ontologies Christoph Dessimoz Thursday Nov. 22 th

27. 27, StarOmics course,Lausanne, Monday November 19 th Importance of the ‘GO evidence tags’

28. 28, StarOmics course,Lausanne, Monday November 19 th GO annotation - manual ‘GO annotators’ read publication and infer GO terms to the corresponding genes according to the information found in the paper. Done by more than 30 external model organism and multi-species database curators including UniProtKB/Swiss-Prot, dictyBase, EcoCyc, FlyBase, Gramene, Human Protein Atlas, IntAct, LifeDB, MGI, PomBase, Reactome, RGD, TAIR, SGD, WormBase and ZFIN. Link to the corresponding paper…(PubMed ID)

29. 29, StarOmics course,Lausanne, Monday November 19 th Histone H4: annotation according to paper content

30. 30, StarOmics course,Lausanne, Monday November 19 th Histone H4: annotation according to paper content : biological mistakes ! !!! Large scale derived data (‘proteome’)

31. 31, StarOmics course,Lausanne, Monday November 19 th Lack of consistency between species

32. 32, StarOmics course,Lausanne, Monday November 19 th Be careful…

33. 33, StarOmics course,Lausanne, Monday November 19 th 33 http://www.metanetx.org/ RTD project of SystemsX.ch –J. Stelling, –I. Xenarios, –W. Gruissem, –U. Sauer, –V. Hatzimanikatis –D. Kossmann –M. Pagni

34. 34, StarOmics course,Lausanne, Monday November 19 th 34 A Knowledge-Based Bioinformatics Framework for Microbial Pathway Genomics www.microme.eu Microme is an EU Framework Programme 7 Collaborative Project. Microme is a resource for bacterial metabolism, whose aim is to support the large scale inference of metabolic flux directly from genome sequence.

35. 35, StarOmics course,Lausanne, Monday November 19 th StarOmics training agenda Chemicals Reactions Enzymes Pathways Introduction Available resources Exercises

36. 36, StarOmics course,Lausanne, Monday November 19 th http://education.expasy.org/cours/StarOmics2012/