GOA December 2013

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UniProt Gene Ontology Annotation Summary, December 2013


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 430,000 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 35 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 January 2013 and November 2013, the UniProt-GOA project provided the GO Consortium with 11 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 almost 208 million GO annotations for almost 32 million proteins in over 437,000 different taxonomic groups. UniProt-GOA provides 269,426 annotations for the 20,730 proteins in the human reference proteome.

UniProt-GOA UniProt gene association file release stats (comparison of January 2013 and November 2013 releases)

GOA Stats 2013a.png GOA Stats 2013b.png


*Reduction in WormBase annotation due to cleaning up of data during migration into UniProt-GOA database

**New sources of annotation after January 2013

Methods and strategies for annotation

Literature curation:

During 2013 we started a curation project to annotate proteins that are experimentally determined to be located in the extracellular vesicular exosome (A membrane-bounded vesicle that is released into the extracellular region by fusion of the limiting endosomal membrane of a multivesicular body with the plasma membrane). The composition of exosomes can vary depending on the cell type they were released from, this information can be captured in the annotation extension to provide valuable contextual information for each protein.

We have also been involved in recuration of annotations for apoptosis and necroptosis following the ontology development projects in these areas. This involved reviewing annotations to high-level apoptosis terms and re-reading publications to determine if a more granular term could be used instead.

Finally we are annotating 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.

Computational annotation:

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 125 million annotations to almost 19 million proteins.

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

UniProt Consortium. 2013. Update on activities at the Universal Protein Resource (UniProt) in 2013. Nucleic Acids Res. 2013 Jan;41(Database issue):D43-7. PMC3531094

Tripathi S, Christie KR, Balakrishnan R, Huntley R, Hill DP, Thommesen L, Blake JA, Kuiper M, Lægreid A. Gene Ontology annotation of sequence-specific DNA binding transcription factors: setting the stage for a large-scale curation effort. 2013. Database (Oxford). 2013 Aug 27;2013:bat062. PMC3753819

Balakrishnan R, Harris MA, Huntley R, Van Auken K, Cherry JM. 2013. A guide to best practices for Gene Ontology (GO) manual annotation. Database (Oxford). 2013 Jul 9;2013:bat054. PMC3706743

The Gene Ontology Consortium. 2013. Gene Ontology Annotations and Resources. Nucleic Acids Research, 41(Database issue), D530-535. PMC3531070

Mutowo-Meullenet P, Huntley RP, Dimmer EC, Alam-Faruque Y, Sawford T, Jesus Martin M, O'Donovan C, Apweiler R. 2013. Use of Gene Ontology Annotation to understand the peroxisome proteome in humans. Database (Oxford). 2013 Jan 17;2013:bas062. PMC3548334

b. Presentations including Talks, Tutorials and Teaching

Rachael Huntley. The Gene Ontology Resource - Common Misconceptions and Improving Accuracy. Automated Function Prediction SIG at ISMB/ECCB July 20 2013, Berlin, Germany. (talk).

Rachael Huntley. Using the Gene Ontology. EMBL-EBI Industry Programme Workshop: "A practical overview of biomedical ontologies". April 17-18 2013, Hinxton, UK. (Hands-on tutorial).

Prudence Mutowo. Use of Gene Ontology Annotation to understand the peroxisome proteome in humans. 2013 International Biocuration Conference, April 7-10, Cambridge, UK. (talk).

Prudence Mutowo. EBI Bioinformatics Roadshow January 2013 Zimbabwe. (Hands-on tutorial).

c. Posters

The UniProt-GOA resource. EMBL-EBI Open Day, Hinxton. November 7 2013. Prudence Mutowo and Aleksandra Shypitsyna.

The Gene Ontology Resource - Common Misconceptions and Improving Accuracy. Automated Function Prediction SIG at ISMB/ECCB July 20 2013, Berlin, Germany. Rachael Huntley.

Protein2GO: A curation tool for Gene Ontology. 2013 International Biocuration Conference, April 7-10, Cambridge, UK. Rachael Huntley.

The UniProt-GOA resource. EMBL-EBI Open Day, Hinxton. March 14 2013. Rachael Huntley.

Ontology Development Contributions

  • Rachael Huntley was part of the cell cycle ontology development meeting to discuss changes to the cell cycle node of the ontology. This was held on 28th February-1st March in EMBL-EBI, Hinxton
  • All curators continue to request new GO terms or updates to the ontology where necessary, using either Term Genie or the SourceForge tracker

Annotation Outreach and User Advocacy Efforts

  • Rachael Huntley and Prudence Mutowo-Meullenet trained two new UniProt (EBI) curators in GO annotation
  • Rachael Huntley and Prudence Mutowo-Meullenet trained two GeneDB curators in GO annotation
  • 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, 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. Both WormBase and SGD completed this transition in 2013.
  • Access and training for the Protein2GO curation tool has been given to curators from the CamCellNet cilial protein curation project.
  • 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. Two meetings have been held at the EBI during 2013, the first (7-8 February) to discuss annotation guidelines and incorporation of annotations and second, a curation tool workshop on 26 September. This collaboration has so far resulted in one publication.
  • As part of the continuing exosome annotation project, Prudence Mutowo-Meullenet is in contact with the ExoCarta database to assist them in providing UniProt with annotations they have for exosome proteins.
  • 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

Other Highlights

i. Improvements to the QuickGO user interface

Work to improve the QuickGO user interface has continued throughout 2013. QuickGO will retain all of its current functionality but is designed to be more intuitive to use.

ii. Improvements to the Protein2GO curation tool

As more GO Consortium curation groups migrate their annotations into the UniProt database and move to using Protein2GO as their sole curation tool for protein GO annotation, we have been adding features to assist these groups in searching for MOD identifiers they are more familiar with. Protein2GO can now be used to search for specific MOD IDs and return the equivalent UniProt accession(s). An indication is given as to whether the UniProt accession is reviewed or unreviewed. Curators from other MODs are also able to put MOD identifiers into the 'with' field.

Another addition was a Literature Search link that allows GO curators to perform keyword searches on nine different Textpresso corpora from within Protein2GO.

As GO curation guidelines evolve, we continue to add quality control checks into Protein2GO to prevent incorrect annotations from being created. These include;

  • Prevention of ISS annotations to blacklisted GO term:protein combinations
  • Prevention of 'NOT' qualified annotations when an annotation extension is present
  • Warn curators if they update a UniProt accession of an annotation that has been copied to other proteins

Other features implemented include;

  • Ability to dispute electronic annotations
  • Allow ISS annotations to be made to a less granular term
  • Implemented subsets for annotation extension relations, which simplifies use of this field for the curator
  • Ability to make a comment on ISS annotations to indicate how the group of target proteins was chosen
  • Provision of a link out to Textpresso, used by various MODs
  • Ability to use the new format UniProt accession
  • Further SQL-based query reports in response to curator's needs

November 2013

In our 125th release of the multispecies UniProt file, we supplied over 200 million annotations to over 30 million proteins from all our collaborating groups.

October 2013

Manual annotations are now being integrated into our files for several bacterial and viral species as provided by the Community Assessment of Community Annotation with Ontologies (CACAO), a project to provide large-scale manual community annotation of gene function using the Gene Ontology. Details of the CACAO project can be found at: http://gowiki.tamu.edu/wiki/index.php/Category:CACAO

The CACAO annotations can be viewed in QuickGO: http://www.ebi.ac.uk/QuickGO/GAnnotation?source=CACAO

July 2013

We have rationalized the attribution display for UniProt- and Ensembl-created annotations. This attribution is shown in the 'assigned_by' column, which is column 15 of the Gene Association Files (GAF) and column 10 of the Gene Product Assocation Data files (GPAD). UniProt-created annotations all now have the attribution 'UniProt', this includes UniProt manual annotation and automatic annotation based on EC, HAMAP, UniProt keywords, UniProt subcellular location and UniPathway. Ensembl-created annotations all now have the attribution 'Ensembl', this includes the automatic annotation from Ensembl vertebrates, EnsemblFungi and EnsemblPlants/Gramene.

June 2013

Manual annotations are now being integrated into our files for the filamentous fungi, Aspergillus, that have been created by the AspGD Project, as well as manual annotations for Pseudomonas aeruginosa that have been created by the Pseudomonas aeruginosa Community Annotation Project (PseudoCAP).

Details of the AspGD project can be found at: http://www.aspgd.org/ Details of the PseudoCAP project can be found at: http://www.pseudomonas.com/

May 2013

We now release a set of species-specific annotation files that are based on UniProt reference proteomes that 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 are released in both GAF2.0 and GPAD format and there is an accompanying Gene Product Information file, which contains additional information on all the protein accessions in the species' reference proteome.

April 2013

We now supply the species-specific annotation files in GPAD1.1 format.

Manual annotations are now being integrated into our files, for archaeal and bacterial species, that have been supplied by the Microbial ENergy processes Gene Ontology Project (MENGO). Details of the MENGO project can be found at: http://mengo.vbi.vt.edu/

March 2013

We now supply the UniProt annotation file in GPAD1.1 format.

February 2013

We have changed the referencing of GO Cellular Component annotations from the Human Protein Atlas (HPA) and LIFEdb. Previously all HPA annotations were referenced by PMID:18029348 and all LIFEdb annotations by PMID:11256614. These papers describe the pilot studies and methodology used to obtain the annotations rather than experiments for the individual protein localizations. It was decided that these annotations would be more correctly described using a GO reference (GO_REF), which is an abstract describing the methodology behind a set of annotations. The HPA annotations are now referenced by GO_REF:0000052 and the LIFEdb annotations by GO_REF:0000054. Both references are described here: http://www.geneontology.org/cgi-bin/references.cgi