BHF-UCL December 2013

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BHF-UCL

December, 2013

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. BHF-UCL has been a GOC member since July 2008.

1. Staff:

  • Dr Ruth Lovering, 1 FTE – UCL-based curator, BHF scholarship to February 2014, UCL funding to July 2018
  • Dr Anna Melidoni, 1 FTE – UCL-based curator, BHF grant to July 2018
  • Dr Nancy Campbell, 1 FTE – UCL-based curator, BHF grant to July 2018
  • Tony Sawford, 0.25 FTE – EBI-based Software engineer, BHF grant to BHF grant to July 2018

No funding via GOC NIHGRI grant

2. Annotation Progress

The annotation progress reflects the priority of this project to annotate human genes, with 20,503 GO terms associated to 2,322 human proteins (1st November 2007 to 7th December 2013). Across all species BHF-UCL have annotated 4,083 proteins with 29,835 GO terms.

3. Methods and strategies for annotation

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

a. 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. The protein-centric annotation is undertaken when annotating proteins on a specific cardiovascular relevant list, such as a Genome-Wide Association Study. In addition, we annotate proteins following requests from cardiovascular scientists or when annotated by attendees of our MSc module or 2-day annotation workshops. 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.

b. Computational annotation strategies: None used

c. Priorities for annotation: Human genes involved in cardiovascular-related processes, as agreed by the International Scientific Advisory Panel. During the past year we have been focusing on the annotation of cardiac conduction associated genes and the human orthologs of genes that are associated with the process of heart jogging in zebrafish. We are now funded to spend our time equally between annotating using GO terms proteins, microRNAs and capturing protein-protein interactions through the submission of PPIs to IntAct. Currently we are revisiting previously annotated papers to capture PPIs that had been submitted to GO which we are now adding to IntAct.

==4. Presentations and Publications== (Tony Sawford’s publications not listed here as these will be include in the GOA report)

a. Papers with substantial GO content Asselbergs, F. W., Lovering, R. C., & Drenos, F. (2013). Progress in genetic association studies of plasma lipids. Curr Opin Lipidol, 24 (2), 123-128. doi:10.1097/MOL.0b013e32835df2d6

b. Presentations including Talks and Tutorials and Teaching

Annotating the Genome - BCGES Annual Meeting in conjunction with Statistics and South of England Genetic Epidemiology Group London, 12th June 2013 Ruth was invited to give a 20 min presentation entitled: Gene Ontology: progress and priorities for annotating the human genome.

The BHF-UCL GO curators are closely associated with the Cardiovascular Genetics group at UCL and the UCL-London-School-Edinburgh-Bristol (UCLEB) consortium of population-based prospective studies and have given 7 presentations at their group meetings.

The BHF-UCL team is teaching a ‘bioinformatics’ module for Genetics of Human Disease MSc students this year. By focusing on the review of a GWAS risk-associated SNP the students constructively apply their newly acquired knowledge of a variety of online biological resources, including Ensembl, EntrezGene, IntAct, Cytoscape, UniProt, QuickGO, AmiGO, HCOP and functional analysis tools. In addition, the students learn the importance of including full experimental detail in scientific publications.

In April 2013 the BHF-UCL team ran a 2-day GO annotation workshop at UCL. This workshop was attended by 20 UCL scientists who learn how to use some of the freely available biological databases, how to analyse high-throughput datasets and also contributed GO annotations to the GOA database.

c. Poster presentations

Computational Life & Medical Sciences 3rd Annual Symposium London, 28th June 2013 Poster presented by Ruth: The impact of focused Gene Ontology annotation efforts on high-throughput data analysis.

Innovations in Cardiovascular Science Symposium London, 22nd April 2013 Poster presented by Ruth: The impact of focused Gene Ontology annotation efforts on high-throughput data analysis.

Biocuration 2013 Cambridge, 07-10th April 2013 Poster presented by Ruth: The impact of focused Gene Ontology annotation efforts on high-throughput data analysis.

RA Fisher Centre Meeting London, 8th November 2013 Poster presented by Nancy: Gene Annotation at UCL

5. Other Highlights:

A. Ontology Development Contributions:

During the past year Ruth has been involved in the cardiac conduction development working group. The initial working group met in November 2011 at UCL, this meeting brought together GO curators, editors and several UCL based expert scientists. To date 110 GO terms have been created as part of this ontology effort. In addition, since 13th December 2012 the BHF-UCL team have made 31 Source Forge request (to 17/12/13), the majority of which were relevant to cardiovascular processes, for example VEGF-activated neuropilin signalling pathway, structural constituent conferring elasticity and intrinsic apoptotic signaling pathway in response to hypoxia. This brings the total number of GO terms created by the BHF-UCL team to almost 1,800.

B. Annotation Outreach and User Advocacy Efforts:

The BHF-UCL team is teaching a ‘bioinformatics’ module for Genetics of Human Disease MSc students this year. By focusing on the review of a GWAS risk-associated SNP the students constructively apply their newly acquired knowledge of a variety of online biological resources, including Ensembl, EntrezGene, IntAct, Cytoscape, UniProt, QuickGO, AmiGO, HCOP and functional analysis tools. In addition, the students learn the importance of including full experimental detail in scientific publications.

In April 2013 the BHF-UCL team ran a 2-day GO annotation workshop at UCL. This workshop was attended by 20 UCL scientists who learn how to use some of the freely available biological databases, how to analyse high-throughput datasets and also contributed GO annotations to the GOA database.

C. Other Highlights: This year the Initiative has circulated four newsletters, in January, April, August, and November 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 and to the UCL Department of Medicine mailing list and through our web site.

The UCL annotation team was awarded a Parkinson’s UK grant to annotate Parkinson’s disease relevant genes with GO terms. This grant will start on 1st January 2014 and employ Dr Paul Denny 0.5FTE (for 3 years) as a biocurator and to manage the project and 1FTE biocurator for 2 years.