UCL Institute of Cardiovascular Science


October 2015

Editor - Paul Denny

Gene Annotation

As a result of attending the first meeting of the UK Autophagy Network (May 2015), Paul has been annotating proteins involved in regulating autophagy, creating 85 annotations for 14 human proteins, so far.

Rebecca has begun to annotate proteins involved in WNT signalling. She has chosen this process for two reasons, firstly WNT3 is a candidate Parkinson's risk gene (PMID:21812969) and secondly there is accumulating evidence (e.g. PMID:24115276) that de-regulated WNT signalling may be one of the pathological mechanisms leading to PD. This pathway was brought to our attention by Prof. Kirsten Harvey (UCL) at last year's Neuroscience conference. As part of this process focus, Rebecca is annotating another GWAS locus candidate gene, VPS35, encoding a crucial member of the retromer complex. The retromer complex regulates WNT secretion by regulating the stability of 'Wntless/WLS', and we are improving and expanding retromer-related terms in the underlying ontology to ensure highly specific annotations can be created.

At the International Parkinson Disease Genomics Consortium (IPDGC) meeting in September, work was presented by Mark Cookson (NIH), linking together sporadic and familial forms of Parkinson's disease through a common set of genes. Intriguingly, proteins encoded by several GWAS candidate genes (RAB29/RAB7L1, BAG3, GAK) interact in vitro with LRRK2, the protein derived from the best-characterised familial Parkinson's locus. Furthermore, these four proteins function together in a shared biochemical pathway controlling the clearance of trans-Golgi-derived vesicles upstream of autophagy. Consequently, Paul has annotated the functional data for the human proteins described in PMID:24510904 and PMID:25500533; the protein interaction data had already been captured by our colleagues at Intact.

The overall annotation count for the project (September 2nd 2015), so far, is 4281 GO terms associated with 1045 proteins, including 659 human proteins.

Community Engagement

We have substantially revised our module in the MSc 'Genetics of Human Disease', including GO and other Bioinformatic Resources, in order to encourage student engagement and following the example of the UCL Connected Curriculum. This allows us to both pass on expertise and increase awareness of our work on annotating proteins relevant to Parkinson's.

During the summer, Ruth and Rebecca organised, and the whole UCL team participated in, the training of visitors from VU University, Amsterdam, in Gene Ontology (GO) annotation. The aims of this project were to improve the representation of synapse biology in the ontology and also to expand the annotation of proteins involved in synaptic functions; clearly highly relevant to our understanding of Parkinson's. This effort is part of a wider collaboration between the GO Consortium, the Neuroscience Campus at VU Amsterdam University and the Stanley Center at the Broad Institute.

Meetings Attended

Ruth attended the GO Consortium meeting in Washington, DC, giving two presentations entitled: 'PSIQUIC GO annotations' and 'Strategies and templates for independent funding of targeted projects'.

At the IPDGC meeting at the Institute of Neurology, UCL, Paul gave a presentation entitled: 'Parkinson's Disease and Gene Ontology Annotation'. The main feedback from this talk was that the community would appreciate guidance on the choice of the best tools for GO term enrichment analysis; Paul pointed out that some tools are both user-friendly and use up-to-date GO data e.g. VLAD, gprofiler.

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