1. 24th Feb 2006 Jane Lomax GO Further

2. 24th Feb 2006 Jane Lomax GO annotations Where do the links between genes and GO terms come from?

3. 24th Feb 2006 Jane Lomax GO annotations Contributing databases: –Berkeley Drosophila Genome Project (BDGP)Berkeley Drosophila Genome Project (BDGP –dictyBase (Dictyostelium discoideum)dictyBase –FlyBase (Drosophila melanogaster)FlyBase –GeneDB (Schizosaccharomyces pombe, Plasmodium falciparum, Leishmania major and Trypanosoma brucei)GeneDBSchizosaccharomyces pombe –UniProt Knowledgebase (Swiss-Prot/TrEMBL/PIR-PSD) and InterPro databasesUniProt KnowledgebaseInterPro –Gramene (grains, including rice, Oryza)Gramene –Mouse Genome Database (MGD) and Gene Expression Database (GXD) (Mus musculus)Mouse Genome Database (MGD) and Gene Expression Database (GXD) –Rat Genome Database (RGD) (Rattus norvegicus) –ReactomeReactome –Saccharomyces Genome Database (SGD) (Saccharomyces cerevisiae)Saccharomyces Genome Database (SGD) –The Arabidopsis Information Resource (TAIR) (Arabidopsis thaliana)The Arabidopsis Information Resource (TAIR) –The Institute for Genomic Research (TIGR): databases on several bacterial speciesThe Institute for Genomic Research (TIGR) –WormBase (Caenorhabditis elegans)WormBase –Zebrafish Information Network (ZFIN): (Danio rerio)Zebrafish Information Network (ZFIN)

4. 24th Feb 2006 Jane Lomax Species coverage All major eukaryotic model organism species Human via GOA group at UniProt Several bacterial and parasite species through TIGR and GeneDB at Sanger –many more in pipeline

5. 24th Feb 2006 Jane Lomax Annotation coverage

6. 24th Feb 2006 Jane Lomax Anatomy of a GO annotation Three key parts: –gene name/id –GO term(s) –evidence for association

7. 24th Feb 2006 Jane Lomax Example annotation Breast cancer type 1 susceptibility protein gene in humans

8. 24th Feb 2006 Jane Lomax Types of GO annotation:  Electronic Annotation  Manual Annotation

9. 24th Feb 2006 Jane Lomax Manual annotation Created by scientific curators High quality Small number

10. 24th Feb 2006 Jane Lomax Manual annotation In this study, we report the isolation and molecular characterization of the B. napus PERK1 cDNA, that is predicted to encode a novel receptor-like kinase. We have shown that like other plant RLKs, the kinase domain of PERK1 has serine/threonine kinase activity, In addition, the location of a PERK1-GTP fusion protein to the plasma membrane supports the prediction that PERK1 is an integral membrane protein…these kinases have been implicated in early stages of wound response…

11. 24th Feb 2006 Jane Lomax Manual annotation

12. 24th Feb 2006 Jane Lomax Electronic Annotation Annotation derived without human validation –mappings file e.g. interpro2go, ec2go. –Blast search ‘hits’ Lower ‘quality’ than experimental codes

13. 24th Feb 2006 Jane Lomax Mappings files Fatty acid biosynthesis ( Swiss-Prot Keyword) EC:6.4.1.2 (EC number) IPR000438: Acetyl-CoA carboxylase carboxyl transferase beta subunit ( InterPro entry) GO:Fatty acid biosynthesis ( GO:0006633 ) GO:acetyl-CoA carboxylase activity ( GO:0003989 ) GO:acetyl-CoA carboxylase activity (GO:0003989)

14. 24th Feb 2006 Jane Lomax Evidence types ISS: Inferred from Sequence/structural Similarity IDA: Inferred from Direct Assay IPI: Inferred from Physical Interaction IMP: Inferred from Mutant Phenotype IGI: Inferred from Genetic Interaction IEP: Inferred from Expression Pattern TAS: Traceable Author Statement NAS: Non-traceable Author Statement IC: Inferred by Curator ND: No Data available IEA: Inferred from electronic annotation

15. 24th Feb 2006 Jane Lomax GO terms Where do GO terms come from? –most GO terms are added by the GO editorial office at EBI –new terms are usually only added when they are asked for by annotators –GO editors work with experts to make major ontology developments metabolism pathogenesis cell cycle

16. 24th Feb 2006 Jane Lomax GO stats almost 20,000 GO terms –10452 biological_process –1687 cellular_component –7393 molecular_function

17. 24th Feb 2006 Jane Lomax Growth of GO

18. 24th Feb 2006 Jane Lomax No GO Areas GO covers ‘ normal ’ functions and processes –No pathological processes –No experimental conditions NO evolutionary relationships NO gene products NOT a system of nomenclature

19. 24th Feb 2006 Jane Lomax Open Biomedical Ontologies (OBO) A repository for well-structured controlled vocabularies for shared use across different biological and medical domains: http://obo.sourceforge.net/

20. 24th Feb 2006 Jane Lomax Open Biomedical Ontologies (OBO) Requirements for inclusion: http://obo.sourceforge.net/crit.html

21. 24th Feb 2006 Jane Lomax AmiGO exercise

22. 24th Feb 2006 Jane Lomax Annotation exercise We have provided a Nature paper (PMID: 14961121) for you to annotate with GO terms –This will help you to understand how the information is extracted from papers and GO terms are applied by the curators –It will also give you the opportunity to use another GO browser developed at EBI: QuickGO

23. 24th Feb 2006 Jane Lomax Annotation exercise The gene you are annotating is VG5Q –To make it easier we’ve highlighted some of the most relevant passages in the text Use the GO browser QuickGO to look for the most appropriate GO terms: –http://www.ebi.ac.uk/ego/http://www.ebi.ac.uk/ego/

24. 24th Feb 2006 Jane Lomax Annotation exercise In QuickGO, you search for the GO terms by name http://www.ebi.ac.uk/ego/

25. 24th Feb 2006 Jane Lomax Annotation exercise Remember, as well as the GO term, you also need to assign an evidence code –to remind you, we’ve included a list of the evidence codes at the back of the paper

26. 24th Feb 2006 Jane Lomax Annotation exercise To see how your annotations compared to those done by the GO curator, search QuickGO for Q8N302 –This is the UniProt id for the gene VG5Q Click ‘show only manual’ and this will show you the annotations the curator made