1. CACAO Training Fall 2012

2. Community Assessment of Community Annotation with Ontologies (CACAO)

3. Spring 2010Fall 2010Spring 2011Fall 2011 InstitutionsTAMU UCL TAMU Miami (Ohio) North Texas Penn State Michigan State TAMU UCL Swarthmore Mississippi State Hofstra Houston Baptist North Dakota State Wisconsin Wisconsin-Parkside # Rounds1 round4 rounds5 rounds Annotations/ Submitted 118/153496/753723/1018Not finished with assessments/1524 What’s in it for you? – We hope you will learn how we think about protein function gain skills that will help your future career enjoy contributing to a resource used by people all over the world have fun!

4. Annotation Annotation: a note that is made while reading any form of text For scientists, 1.Nucleotide level: Where the genes are in the genome 2.Protein level: What their functions are From Wikipedia

5. Annotation Annotation: a note that is made while reading any form of text For scientists, 1.Nucleotide level: Where the genes are in the genome 2.Protein level: What their functions are From Wikipedia

6. Functional Annotation Annotation: a note that is made while reading any form of text Functional Annotation: a note in a specific format that is made based on evidence in a peer-reviewed paper about the attributes of a protein

7. Functional Annotations Allow us to: –Infer the function of genes Related by common descent Related by similar expression patterns Related by phylogenetic profiles … Allow us to: –Understand the capabilities of organisms’ genomes –Understand patterns of gene expression In different environments In different tissues In disease states …

8. Functional Annotations Finding genes faster than we can understand them

9. Functional Annotations >21 million peer-reviewed articles in PubMed Many millions of proteins recorded in UniProt http://www.uniprot.org

10. Who classically makes functional annotations? Literature Datasets Biocurators (rate limiting) Database

11. Functional Annotations Accurate functional annotation for as many genes as possible A system of assigning function that allows both humans and computers to compare, contrast, analyze, and predict gene function Curators to make and/or check these assignments – For CACAO, we will train you to be biocurators.

12. Functional Annotation Functional Annotation: a note in a specific format that is made based on evidence in a peer-reviewed paper about the attributes of a protein Specific format = GO (Gene Ontology) Annotation

13. GO (Gene Ontology) Annotations 3 aspects (ontologies) for describing protein attributes: 1. Biological Process 2. Molecular Function 3. Cellular Component Controlled vocabulary –Everyone uses the same terms –Terms have 7 digit IDs that computers can understand Relationships between terms GO:0005886

14. Molecular Function activities or “jobs” of a gene product GO:0004347 hexokinase activity From PMID:9341134, rndsystems.com GO:0016301 Kinase activity

15. Biological Process a commonly recognized series of events GO:0051301 cell division From ridge.icu.ac.jp, edtech.clas.pdx.edu, scielosp.org GO:0006351 transcription, DNA dependent GO:0009405 pathogenesis

16. Cellular Component where a gene product acts From visualphotos.com, epmm.group.shef.ac.uk, http://www.cellsignal.com/products/2415.html GO:0005739 mitochondrion GO:0009274 peptidoglycan-based cell wall GO:0005840 ribosome

17. Where can you search for GO terms? GONUTS (gowiki.tamu.edu) -http://gowiki.tamu.eduhttp://gowiki.tamu.edu -http://www.ebi.ac.uk/QuickGOhttp://www.ebi.ac.uk/QuickGO -http://amigo.geneontology.org

22. What do you actually need once you have found the correct term? GO:0004713

23. Functional Annotation Functional Annotation: a note in a specific format that is made based on evidence in a peer-reviewed paper about the attributes of a protein Specific format = GO (Gene Ontology) Annotation Peer-reviewed paper

24. Finding a scientific paper Has to be a scientific paper with experimental data in it. (Anything else is a valid reason to challenge!!) No review articles, no books, no textbooks, no wikipedia articles, no class notes… You will need the PMID number 22110029

25. Functional Annotation Functional Annotation: a note in a specific format that is made based on evidence in a peer-reviewed paper about the attributes of a protein Specific format = GO (Gene Ontology) Annotation Peer-reviewed paper Protein

26. What can you annotate? Proteins. PubMed for papers on a specific topic or protein or GO term Search UniProt for something interesting (i.e. allergen) or a protein of interest (i.e. PcnB) Check the references in the paper you are currently reading No matter what, you will need to find the protein’s accession on UniProt (http://uniprot.org) Use that accession to make a page for that protein on GONUTS (http://gowiki.tamu.edu) Add your GO annotations to the protein’s page on GONUTS

27. Why do you need an accession from UniProt (http://www.uniprot.org)? 1.UniProt is not editable by the community, but GONUTS is. 2.GONUTS can make a page that has the annotations from UniProt for any protein using it’s UniProt accession. 3.Correct & complete annotations at the end of the competition will be submitted back to UniProt. *

28. How do you make a new protein page in GONUTS? 1 1 2 2 GoPageMaker will:  Check if the page exists in GONUTS & take you there if it does.  Make a page if it does not exist in GONUTS already & pull all of the annotations from UniProt into a table that you can edit. Make as many protein pages as you would like!

30. Functional Annotation Functional Annotation: a note in a specific format that is made based on evidence in a peer-reviewed paper about the attributes of a protein Specific format = GO (Gene Ontology) Annotation Peer-reviewed paper Protein

32. Form for your annotation (when you edit the table)

33. 4 REQUIRED parts of EVERY GO annotation GO Evidence code Reference Notes (about evidence)

34. Summary of Evidence Codes for CACAO Evidence codes describe the type of work or analysis done by the authors IDA: Inferred from Direct Assay IMP: Inferred from Mutant Phenotype IGI: Inferred from Genetic Interaction ISO: Inferred from Sequence Orthology ISA: Inferred from Sequence Alignment ISM: Inferred from Sequence Model IGC: Inferred from Genomic Context If it’s not one of these 7, your annotation is incorrect!!! http://gowiki.tamu.edu/wiki/index.php/evidence_codes

35. Functional Annotation Functional Annotation: a note in a specific format that is made based on evidence in a peer-reviewed paper about the attributes of a protein Specific format = GO (Gene Ontology) Annotation Peer-reviewed paper Protein Evidence code

36. 4 REQUIRED parts of EVERY GO annotation GO Evidence code Reference Notes (about evidence)

37. 2 other parts that may rarely be required… With/From Qualifier

38. How is CACAO scored? Rounds Points for a complete AND correct annotation (1 week/round) 4 necessary parts May be additional parts NOTE: We will take away points if the annotation is not correct when assessed by an experienced CACAO biocurator Challenges are used to steal points for incorrect &/or incomplete annotations (1 week/round) Identify a problem Suggest correct alternative Refinements can be entered by any team (during any challenge week)

39. Scoreboard & Challenges

40. Team & Individual Pages challenge

41. Challenges 1.Enter the reason for your challenge here. - (i.e. What’s wrong) 2. Provide the fix(es) for it.

42. I don’t think IGI is appropriate for this annotation. IGI uses multiple strains or organisms to compare. The evidence listed is just showing mutations in the protein and it’s effects on Dynamin-1, endophilin, and GluR1. The evidence code should be changed to IMP instead, and the other two annotations will probably need to be deleted. * Example Challenge

43. Multiple Challenges = Potentially More Points!

44. Scoreboard

45. UniProt – http://uniprot.orghttp://uniprot.org –Find your protein(s) here (UniProt accession required) PubMed – http://pubmed.orghttp://pubmed.org –Find your papers about the protein’s attributes (molecular function, biological process, cellular component) GONUTS – http://gowiki.tamu.eduhttp://gowiki.tamu.edu –Search for GO terms –Make page for your protein on GONUTS (using UniProt accession) –Add your annotation to the protein’s Annotation table during first (Annotation) week of any round –Review and challenge competitors’ annotations during the second (challenge) week of any round