UniProt-GOA Dec 5-March 3

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The UniProt GO Annotation project (UniProt-GOA) at the European Bioinformatics Institute has been a member of the GO Consortium since 2001. All UniProt curators are actively involved in curating UniProtKB entries with Gene Ontology terms during the UniProt literature curation process, providing both high-quality manual GO annotations in addition to their contributions to electronic GO annotation pipelines. The multi-species nature of UniProtKB means that the GO Annotation project is able to assist in the GO curation of proteins from over 450,000 taxonomic groups.

The core UniProt-GOA project staff are primarily responsible for supplying the GO Consortium with manual and electronic GO annotations to the human proteome. UniProt-GOA staff not only manually annotate, but coordinate and check the integration of GO annotations from other curation efforts at the EBI (including from InterPro, IntAct and Reactome). The UniProt-GOA dataset is supplemented with manual annotations from 40 annotating groups, including all members of the GO Consortium, as well as a number of external groups which produce relevant functional data. Nine electronic annotation pipelines are incorporated into the UniProt-GOA dataset, which provide the vast majority of annotations for non-model organism species. UniProt-GOA is therefore able to consolidate multiple sources of specialised knowledge, ensuring the UniProt-GOA resource remains a key up-to-date reference for a large number of research communities.


Claire O'Donovan

Maria Martin

Rachael Huntley*

Prudence Mutowo-Muellenet

Tony Sawford*

Aleksandra Shypitsyna

Carlos Bonilla

UniProt contributors (EBI, Hinxton, UK; SIB, Geneva, Switzerland; and PIR, Washington DC): Ioannis Xenarios, Lydie Bougueleret

Ghislaine Argoud-Puy, Andrea Auchinchloss, Kristian Axelsen, Marie-Claude Blatter, Emmanuel Boutet, Lionel Breuza, Alan Bridge, Gayatri Chavali, Elena Cibrian-Uhalte, Elizabeth Coudert, Isabelle Cusin, Paula Duek Roggli, Anne Estreicher, Livia Famiglietti, Marc Feuermann, Arnaud Gos, Nadine Gruaz-Gumowski, Reija Hieta, Ursula Hinz, Chantal Hulo, Janet James, Florence Jungo, Guillaume Keller, Kati Laiho, Duncan Legge, Philippe Lemercier, Damien Lieberherr, Michele Magrane, Patrick Masson, Ivo Pedruzzi, Klemens Pichler, Diego Poggioli, Sylvain Poux, Catherine Rivoire, Bernd Roechert, Michel Schneider, Andre Stutz, Shyamala Sundaram, Michael Tognolli

* Funded entirely or partially by GO.

Annotation progress

Between 5 December 2013 and 3 March 2014, the UniProt-GOA project provided the GO Consortium with 3 annotation file releases, including non-redundant sets of GO annotations to 13 specific proteomes, as well as data releases for annotations of all proteins in UniProtKB.

UniProt incorporates manual annotations from other GO Consortium members and affiliates and displays these annotations in the relevant UniProtKB entries. Currently, the UniProt-GO Annotation project provides GO annotations for 65% of UniProt entries. Altogether, UniProt-GOA now provides over 246 million GO annotations for almost 35 million proteins in over 452,000 different taxonomic groups. UniProt-GOA provides 283,095 annotations for 18,380 proteins (out of a total of 20,644 proteins) in the human reference proteome.

UniProt-GOA UniProt gene association file release stats (comparison of December 2013 and February 2014 releases)

GOA Stats a.png GOA Stats b.png


*New sources of annotation after November 2013

Methods and strategies for annotation

a. Literature curation

In May 2013 we initiated the annotation of a list of approximately 400 human proteins that are targets of the Critical Assessment of Functional Annotation (CAFA) competition. We are curating the primary functions and processes of these proteins in order to populate these targets with functional annotations, which will assist in the assessment of the CAFA competition.

We continue to annotate proteins that are experimentally determined to be located in the extracellular vesicular exosome.

We have also been involved in recuration of annotations for necroptosis following ontology development in this area. This involved reviewing annotations and re-reading publications to determine if a more granular term could be used instead.

b. Computational annotation strategies

UniProt-GOA provides IEA annotations from the following methods:

  1. UniProt Keyword 2GO (SPKW2GO)1,2
  2. UniProt Subcellular Locations2GO (SPSL2GO)1,2
  3. Unipathway2GO1,2
  4. HAMAP2GO1,2
  5. InterPro2GO
  6. Ensembl Compara (vertebrates)
  7. Ensembl Genomes Compara (plants, fungi)


1: mapping tables created and maintained by UniProt

2: electronic annotations generated by UniProt

UniProt curators supply information to entries that is subsequently used in electronic GO annotation pipelines such as UniProtKB keywords2GO, UniProtKB subcellular location2GO and HAMAP2GO. Altogether, automatic annotation pipelines provide almost 245 million annotations to almost 35 million proteins.

c. Priorities for annotation

1. Proteins associated with the exosome (Prudence, Aleksandra)

2. Proteins from the CAFA target list (all curators)

3. Requests from user community (all curators)

4. Proteins annotated during Swiss-Prot curation duties (all Swiss-Prot/UniProtKB curators at the EBI and SIB)

5. Annotation corrections based on quality control reports (all curators)

Presentations and Publications

a. Publications

One publication has been accepted by GigaScience: "Understanding how and why the Gene Ontology and its annotations evolve: the GO within UniProt." Rachael P Huntley, Tony Sawford, Maria J Martin and Claire O'Donovan.

The following three publications have been submitted for publication:

"A method for increasing expressivity of Gene Ontology annotations using a compositional approach." Rachael P Huntley, Midori A Harris, Yasmin Alam-Faruque, Judith A Blake, Seth Carbon, Heiko Dietze, Emily C Dimmer, Rebecca E Foulger, David P Hill, Varsha K Khodiyar, Antonia Lock, Jane Lomax, Ruth C Lovering, Prudence Mutowo-Meullenet, Tony Sawford, Kimberly Van Auken, Valerie Wood and Christopher J Mungall. Submitted to BMC Bioinformatics.

"Representing Kidney Development Using The Gene Ontology." Yasmin Alam-Faruque; David P. Hill; Emily C. Dimmer; Midori A. Harris; Rebecca E. Foulger; Susan Tweedie; Helen Attrill; Douglas G. Howe; Stephen Randall Thomas; Duncan Davidson; Adrian S. Woolf; Judith A. Blake; Christopher J. Mungall; Claire O'Donovan; Rolf Apweiler; Rachael P. Huntley. Submitted to PlosOne.

"Taking care of DNA binding transcription factors." Sushil Tripathi, Karen R. Christie, Judith A. Blake, Rachael P. Huntley, Sandra Orchard, Henning Hermjakob, Liv Thommesen, Martin Kuiper, Astrid Lægreid. Submitted to Nature Genetics.

b. Presentations including Talks, Tutorials and Teaching

Huntley RP. Introduction to the Gene Ontology and GO annotation resources. 12 Jan 2014 Plant and Animal Genome Conference, San Diego, CA USA (Talk)

c. Posters

Other highlights

A. Ontology development contributions

  • All curators continue to request new GO terms or updates to the ontology where necessary, using either Term Genie or the SourceForge tracker

B. Annotation outreach and user advocacy efforts

  • Rachael Huntley trained eight UniProt (EBI and SIB) curators in GO annotation in January
  • Rachael Huntley demonstrated the Protein2GO curation tool to new AgBase curators
  • Rachael Huntley and Prudence Mutowo-Meullenet continue to answer queries sent to the GO Consortium helpdesk
  • Rachael Huntley, Prudence Mutowo-Meullenet and Aleksandra Shypitsyna continue to answer user queries sent to the UniProt-GOA project
  • UniProt is continuing to support external annotation groups, such as AgBase, BHF-UCL, DictyBase, SGD, CamCellNet, WormBase, DFLAT at Tuft's University, SIB and PIR by providing use of the Protein2GO curation tool.
  • UniProt is continuing to assist GO Consortium groups with migration of their annotations into the UniProt database, as well as providing access and training for the UniProt curation tool Protein2GO.
  • Access and training for the Protein2GO curation tool has been given to curators from the Parkinsons and Alzheimers protein curation projects.
  • Rachael Huntley is involved in a GO Consortium collaboration with a team at the Norwegian University of Science and Technology to assist them in making annotations for transcription factors and their target genes. A follow-up meeting was held at the EBI in January to further discuss annotation guidelines and incorporation of annotations. A second publication from this collaboration has been submitted.
  • Together with Rama Balakrishnan from SGD, Rachael Huntley is a manager for the GO Consortium's Annotation Advocacy and Coordination group. The aims of the group are to;
  * educate GO Consortium curators about best annotation practice
  * enforce the annotation rules and policies within the GOC
  * maintain the annotation and evidence code documentation
  * educate and keep all the annotating groups up-to-date with changes in GAF format and ontology development 
  * assist new groups with annotations

C. Other highlights

i. Improvements to the QuickGO user interface

Work is continuing on a new user interface for the UniProt GO browser QuickGO. New features will include the ability to view the Evidence Code Ontology in the ancestor chart view and also to display annotation extensions. This work is being carried out by Carlos Bonilla with support from Tony Sawford.

ii. Improvements to the Protein2GO curation tool

We are continuing to migrate annotations from GO Consortium curation groups into the UniProt database as needed. This also involves each group annotating to proteins using Protein2GO as their sole curation tool.

UniProt-GOA is moving towards using ECO codes in the database and curation tool. To this end, Protein2GO now displays ECO codes alongside the equivalent GO evidence codes. The next step will be to allow curators to use more granular ECO codes when creating an annotation. Tony Sawford is responsible for the development and maintenance of Protein2GO and the UniProt-GOA database.

iii. Annotation file changes

February 2014

1. We have made further improvements to the pipeline that creates the GO Consortium 'inferred' annotations to reduce redundancy. This has caused a large decrease in the number of annotations that are assigned by 'GOC'.

2. Since January we have included annotations from a new project "Parkinson's UK-UCL", which is a project led by Dr. Ruth Lovering at University College London to annotate proteins involved in Parkinson's disease. Further information on this project can be found at http://www.ucl.ac.uk/cardiovasculargeneontology/cardiovascular/newsletters.

January 2014

1. We have suspended submission to the GO Consortium (GOC) of species-specific Gene Association Files if another group is responsible for the provision of GO annotations to that species. This affects the following files:

gene_association.goa_arabidopsis gene_association.goa_mouse gene_association.goa_rat gene_association.goa_zebrafish

These files will no longer be available from the GOC annotation download webpage (http://www.geneontology.org/GO.downloads.annotations.shtml) nor the GOC ftp site (ftp://ftp.geneontology.org/pub/go/gene-associations/submission/). Users will still be able to get annotations for all of these species from the UniProt multispecies file on the GOC website (http://www.geneontology.org/GO.downloads.annotations.shtml#unfilter).

The above species-specific files will continue to be made available from the UniProt-GOA ftp site (ftp://ftp.ebi.ac.uk/pub/databases/GO/goa/).

2. All of the archived species-specific files mentioned above have been removed from the GOC CVS repository. These archived files will still be available from ftp://ftp.ebi.ac.uk/pub/databases/GO/goa/old/

3. In the January release there was a substantial increase in GO Consortium 'inferred' annotations. These annotations are automatically created based on inter-ontology links between Molecular Function and Biological Process terms and between Biological Process and Cellular Component terms. The increase is due to enhancements to the pipeline to take account of the GO hierarchy.

4. Manual annotations for Trypanosoma brucei and Leishmania major, created by the GeneDB project, are now included in the UniProt multi-species annotation files.

December 2013

Changes to the provision of UniProt GO annotation files to the GO Consortium.

1. As of the December release we are additionally supplying the GO Consortium (GOC) with a set of species-specific annotation files for human, dog, pig, cow and chicken that are based on UniProt reference proteomes and provide one protein per gene. The protein accessions included in these files are the protein sequences annotated in Swiss-Prot or the longest TrEMBL transcript if there is no Swiss-Prot record. The files will be available in both GAF2.0 and GPAD1.1 format and can be identified by the inclusion of "ref" in the file name, e.g. gp_association.goa_ref_human. The GAF2.0 files will be available from the GOC annotation downloads page (http://www.geneontology.org/GO.downloads.annotations.shtml) and the GOC ftp site (ftp://ftp.geneontology.org/pub/go/gene-associations/); the locations of the GPAD files will be announced at a later date.

These files are already available from the UniProt-GOA ftp site: ftp://ftp.ebi.ac.uk/pub/databases/GO/goa/