cacao training fall 2012. community assessment of community annotation with ontologies (cacao)

CACAO Training

Fall 2012

Community

Assessment of

Community

Annotation with Ontologies

(CACAO)

Spring 2010 Fall 2010 Spring 2011 Fall 2011

Institutions TAMU TAMUUCL

TAMUMiami (Ohio)North TexasPenn StateMichigan State

TAMUUCLSwarthmoreMississippi StateHofstraHouston BaptistNorth Dakota StateWisconsinWisconsin-Parkside

# Rounds 1 round 4 rounds 5 rounds 5 rounds

Annotations/Submitted

118/153 496/753 723/1018 Not 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!

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

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

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

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• …

Functional Annotations

• Finding genes faster than we can understand them

Functional Annotations

• >21 million peer-reviewed articles in PubMed• Many millions of proteins recorded in UniProt

http://www.uniprot.org

Who classically makes functional annotations?

Literature

Datasets

Biocurators(rate limiting)

Database

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.

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

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

Molecular Function• activities or “jobs” of a gene product

GO:0004347 hexokinase activity

From PMID:9341134, rndsystems.com

GO:0016301 Kinase activity

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

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

Where can you search for GO terms? GONUTS (gowiki.tamu.edu)

- http://gowiki.tamu.edu- http://www.ebi.ac.uk/QuickGO- http://amigo.geneontology.org

What do you actually need once you have found the correct term?

GO:0004713

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

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

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

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

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.

*

How do you make a new protein page in GONUTS?

1

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!

Annotations

edit table

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

Annotations

edit table

Form for your annotation (when you edit the table)

4 REQUIRED parts of EVERY GO annotation

GOEvidence

code

ReferenceNotes (about evidence)

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

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

4 REQUIRED parts of EVERY GO annotation

GOEvidence

code

ReferenceNotes (about evidence)

2 other parts that may rarely be required…

With/From

Qualifier

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)

Scoreboard & Challenges

Team & Individual Pages

challenge

Challenges

1. Enter the reason for your challenge here. - (i.e. What’s wrong)

2. Provide the fix(es) for it.

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

Multiple Challenges = Potentially More Points!

Scoreboard

• UniProt – http://uniprot.org– Find your protein(s) here (UniProt accession required)

• PubMed – http://pubmed.org– Find your papers about the protein’s attributes (molecular function,

biological process, cellular component)

• GONUTS – http://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