BHF-UCL December 2009

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BHF-UCL Summary, 2009

Overview

The aim of the Cardiovascular GO Annotation Initiative (BHF-UCL, British Heart Foundation – University College London) is to provide GO annotation to human cardiovascular-associated genes. This project represents a successful collaboration between University College London (UCL) and the European Bioinformatics Institute (EBI); the annotations created by the UCL-based curators are made directly into the GOA database at the EBI. 4000 human genes have been identified as associated with cardiovascular processes and annotation priorities are agreed on an annual basis in consultation with the Co-Grant holders, the International Scientific Advisory Committee and the UCL-based GO curators. The Initiative aims to comprehensively annotate 1500 genes in 5 years. BHF-UCL has been a GOC member since July 2008.

Staff

Dr Ruth Lovering, 1 FTE – Curator, BHF grant to November 2012

Dr Varsha Khodiyar, 0.8 FTE – Curator, BHF grant to May 2013

No funding by GOC NIHGRI grant

Annotation Progress

The annotation progress reflects the priority of this project to annotate human genes, with 5710 GO terms associated to 882 human proteins (1st November 2007 to 20th November 2009). Across all species BHF-UCL have annotated 1,439 proteins with almost 11,000 GO terms.

Methods and strategies for annotation

(please note % effort on literature curation vs. computational annotation methods)

Literature curation: 100%

The aim of this Initiative is to provide complete and deep annotation of 300 human proteins per year. This is achieved through both protein-centric and process-centric targeting of proteins to annotate. The process-centric annotation enables the curators to gain a better understanding of the targeted a process and using the GONUTs table ensure that relevant terms are associated with all proteins involved in a particular process. The protein-centric annotation is undertaken when annotating proteins on the reference genome list. The following approaches are taken to achieve this:

  • To ensure a rapid improvement in the annotations available for a large number of cardiovascular associated proteins the curators spend a maximum of one day researching the literature associated with each protein.
  • The protein will be marked as ‘complete’ if the curator feels there are no further terms to add.
  • If complete annotation cannot be achieved in a day, the protein record is marked as first pass complete. The intention is to revisit these first pass proteins, hopefully with some expert scientist input, in the following year.
  • The approved gene symbol (and relevant gene and protein aliases) are used to query a variety of biomedical search engines, including NCBI PubMed, iHOP and GOPubMed, to identify suitable papers for the GO annotation of each target protein (with highly researched genes the search is usually limited to human entries only).
  • The curators will usually associate GO terms to all of the human proteins mentioned in each paper read, depending on the experimental evidence available (occasionally GO terms are associated with non-human proteins too).
  • Preference is given to the use of experimental-based evidence codes, however these are only used when the curator is completely confident of the identity of the protein and its derivative species.
  • Reviews are also used to provide an overview of the characteristics of a protein and an insight into the complete set of GO terms required.
  • Experimental data relating to model organism proteins maybe included in our GO annotation process, through the direct annotation of the model organism protein and the use of the ‘inferred by sequence similarity’ evidence code to transfer the information to the orthologous human protein.
  • When experimentally supported literature is unobtainable, due to insufficient information about the species the protein is derived from, the lack of access to a referenced paper, or simply because the knowledge is considered so well accepted that references are not supplied, author statements are used.
  • When possible we associate the chronologically first paper that provides experimental evidence for the characteristic features of a given human protein.
  • We aim to capture the knowledge about each protein using a limited number of papers, with experimental evidence.
  • We do not annotate all relevant papers, if this will lead to repeated duplication of GO terms associated to the protein.
  • GO terms are chosen by querying the GO files with QuickGO or AmiGO.
  • Before assigning a GO term, its definition and position within the ontology are checked to ensure its suitability.
  • The GO editorial office is contacted, via SourceForge, when a new GO term is required, or modifications are needed to an existing GO term.

Computational annotation strategies

None used

Priorities for annotation

Human genes involved in cardiovascular-related processes, as agreed by the International Scientific Advisory Panel

Presentations and Publications

GO 2009 Publications, Tutorials & Workshops, Presentations, Posters, and Resources

Other Highlights

Ontology Development Contributions

Varsha organized a heart development ontology workshop at UCL, in September 2009, which led to the creation of 250 new heart development GO terms.

In addition, since 18/09/08 the BHF-UCL team have made 246 Source Forge request (to 09/12/09), which have led to the creation of 323 new GO terms. The majority of these requests were relevant to cardiovascular processes, for example heart septum morphogenesis, aorta smooth muscle tissue morphogenesis, sarcoplasmic reticulum calcium ion transport, lipoprotein receptor binding, triglyceride homeostasis, beta-catenin-TCF7L2 complex, detection of hypoxia, thrombin receptor signaling pathway and cholesterol import. Varsha’s review of SMAD signalling pathways has led to a discussion about revising the TGF-beta signalling, BMP signalling and SMAD signalling ontologies.

Annotation Outreach and User Advocacy Efforts

The BHF-UCL GO curators are closely associated with the Cardiovascular Genetics group at UCL and have given 6 presentations at their group meetings.

Other Highlights

This year the Initiative has circulated four newsletters, in January, April, July, and October by direct email to the International Advisory Committee and individuals who have expressed an interest in this project; by indirect email, though the mailing lists of several cardiovascular related societies, as hardcopies at meetings and through our web site. In March, Ruth and Varsha attended the London Hypertension Society and London Vascular Biology Forum and distributed leaflets describing the Cardiovascular GO Annotation Initiative project.