The Functional Gene Annotation team captures the following functional information for cardiovascular-relevant gene products.
Gene Ontology (GO)
We use the GOA curation tool to associate terms from the GO to gene products including proteins, RNAs and macromolecular complexes. The data we produce is incorporated into the GOA and GO Consortium databases.
the IntAct editing tool to capture interactions at a very detailed level as described in the IMEx guidelines. These annotations are directly incorporated
into the IntAct database, from where they are exported to the IMEx Consortium
We are manually capturing protein-protein interaction (PPI) experimental data from the cardiovascular-related literature and submitting this to the IntAct public dataset at EBI. This data is then incorporated into the IMEx Consortium dataset. These annotations will contribute to the expansion and development of the existing PPI network and advance our knowledge about protein interactions within the cardiovascular system.
We are currently focusing on re-annotating papers which we had previously identified as including PPI experimental data, during the previous cardiovascular GO annotation Initiative. For example, the interaction between DVL1 and DVL3 described by Kishida et al, 1999, was captured as a GO annotation in 2008. This interaction is now in the IntAct and IMEx datasets and can therefore be included in software creating PPI networks.
Current PPI annotation projects:
- Cardiac conduction (Ruth)
- Lipid traits (Nancy, Mila)
- Telomeres (Nancy)
- Wnt signalling (Anna)
- Heart development (Mila)
Annotation progress can be viewed either using this link or using the IntAct browser, with the advanced fields search option and selecting from 2 drop down menus field: dataset, cardiac. These approaches both retrieve a list of interactions, which can either be downloaded or viewed using the graph tab.
Our additional PPIs have improved the networks
available for individual proteins, for example the number of PPIs associated
with ABCA1 has more than doubled by increasing from 21 to 54 interactions (including duplicated and self-interactions).
We are manually annotating proteins thought or known to play a role in cardiovascular systems through the application of Gene Ontology (GO) terms. Manual annotation is a time-consuming process but provides highly descriptive annotations. The UCL team in general takes a process-focused approach when prioritising which gene products to annotate. The advantage of a process-focused annotation approach is that it gives the curators time to fully understand the biological area they are annotating and consequently provide highly descriptive annotations. In addition, the curators request very descriptive GO terms, because they are keen to improve the annotation of this domain. Finally each paper is fully annotated, which may not happen when curators are taking a gene product focused approach.
Current GO annotation projects:
- Cardiac conduction (Ruth)
- Telomerase and telomere-related proteins (Nancy and Jess)
- Heart development (Alexander Deng, MSc project student)
Previous GO annotation projects:
- Proteins involved in miRNA processing (Rachael)
- Folic acid metabolism (Hadil Alrohaif, MSc project student)
- Hereditary hemochromatosis (Klaus Mitchell, MSc project student)
- Apoptosis (Ruth)
- Heart development (Varsha, Ruth)
- Insulin signaling (Ruth)
- Lipid metabolism (Ruth)
- Immunity (Evelyn)
- Notch Pathway in Cardiac Development (Greg Rowe, MSc project student)
- Transcription factors associated with heart development (Varsha)
- Heart jogging (Varsha)
- BMP signalling pathway (Varsha)
- Inhibitory SMAD signalling pathway (Varsha)
- Growth factor regulated SMAD signalling pathway (Varsha)
- TGF-beta regulated SMAD signalling pathway (Varsha)
- Inositol 1,4,5-triphosphate-sensitive calcium-release channel pathway (Varsha)
- Growth hormone release pathway (Varsha)
- Reverse cholesterol transport (Ruth)
- Ryanodine-sensitive calcium-release channel activity (Varsha)
- Telomere maintenance (Ruth, Nancy)
- Transcriptional regulation by TCF7L2 (Ruth)
- Vitamin D metabolism (Varsha)
- Lipid trait risk associated genes (Ruth)
- CAFA2 project list (Anna, Ruth)
Since January 2015 we have been using the Gene Ontology (GO) to describe the biological roles of microRNAs (miRNAs). Our aim is to to curate miRNAs involved in
cardiovascular development and related processes. Alongside this we have curated the roles of the key human proteins involved in
miRNA processing, such as Drosha and Dicer.
Any queries about the miRNA project should be directed to Rachael Huntley.
Current annotation projects
- BHF-funded research papers (Rachael)
- Cardiac regeneration (Rachael and Barbara)
- Aortic aneurysm (Zara Umrao, MSc project student)
Past annotation projects
- Cardiac conduction (Rachael)
How we annotate miRNAs
miRNA curation guidelines
As part of this project we have drawn up miRNA curation guidelines, in consultation with the Gene Ontology Consortium and experts in miRNA research, which cover how a curator should translate into GO annotations the common experimental assays used to investigate miRNA function, including how to annotate experimentally verified targets of miRNAs as well as the physiological effects that silencing has on the cell or organism.
View the miRNA curation guidelines