Using Gene Ontology (GO) to Characterise
GENEONTOLOGY
Key Players in Parkinson’s Disease
Unifying Biology
Rebecca E. Foulger1, Paul Denny1, Claire O’Donovan3, John Hardy2 and Ruth C. Lovering1
1. Centre for Cardiovascular Genetics, Institute of Cardiovascular Science, University College London, Rayne Building, 5 University Street, London, WC1E 6JF
2. Department of Molecular Neuroscience, Institute of Neurology, University College London, Queen Square, London, WC1N 3BG
3. European Bioinformatics Institute (EMBL-EBI), European Molecular Biology Laboratory, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SD
Introduction to GO
Symptoms and Genetics of Parkinson’s Disease
•  The Gene Ontology (GO) project is a collaborative effort to provide consistent
descriptions of gene products across all Kingdoms of life, and is a key resource for
researchers wishing to understand the biological role of a gene product.
•
Parkinson’s Disease is a progressive neurological condition resulting from loss
of dopamine-producing neurons in the substantia nigra, a region of the brain
controlling balance and movement.
•  GO contains three structured controlled vocabularies (ontologies) that describe gene
products in terms of their associated biological processes, cellular location and
molecular functions, in a species-independent manner.
•
One in every 500 people have Parkinson’s Disease, and the complex condition
can affect different people in different ways.
•
Motor symptoms of Parkinson’s Disease include:
•  Originally developed in 1998, the ontologies have grown to include nearly 40,000
terms describing a wide range of concepts to differing levels of specificity.
Figure 1: Placement of ‘negative
regulation of neuron apoptotic
process (GO:0043524)’ in the
Gene Ontology.
•
Tremor (shaking)
•
Slowed movement (bradykinesia) or loss of movement (akinesia)
•
Rigidity (stiffness)
•
Non-motor symptoms also affect the day-to-day life of sufferers and include
problems with the bladder, bowel and eyes, sleeping problems, loss of
cognition, depression, dementia, and other mental health effects.
•
There’s currently no cure, but drugs are the main treatment for managing the
symptoms of Parkinson’s.
•
Blue arrows represent is_a relationships
between GO terms
The role genetics plays in the cause and development of Parkinson’s is an
active area of research. Researchers have identified a small number of cases
(less than 5%) where Parkinson’s Disease is inherited and caused by a single
mutation in a gene. These ‘risk’ genes include LRRK2, PARK7 and SNCA (αsynuclein).
•
Purple arrows represent regulates and
negatively_regulates relationships between
GO terms
For most Parkinson’s patients, it is likely that genetic and environmental factors
interact to cause Parkinson’s Disease.
•
Studying the genes involved in Parkinson’s can help identify the cellular
mechanisms and machinery underlying disease risk, onset and progression.
Image taken from OBO-Edit, version 2.3.1
The Parkinson’s UK GO Annotation Project
GO terms are assigned to proteins based
on different evidence:
IDA = inferred from direct assay
IGI = inferred from genetic interaction
IMP = inferred from mutant phenotype
•  GO annotation is the practice of capturing data about a gene product using terms
from the Gene Ontology.
•  Started in January 2014, the Parkinson’s UK GO annotation project is a
collaboration between University College London and the European Bioinformatics
Institute (EMBL-EBI), and is funded by Parkinson’s UK.
Each annotation
is attached to a
reference for
traceability.
•  Our aim is to extend GO annotation into neurological areas and provide highquality Gene Ontology annotations to the products of genes relevant to
Parkinson’s Disease.
•  Working at UCL has already enabled us to establish collaborations with
neuroscience researchers. This will feed back into further development of the
Gene Ontology itself, as we expand and improve areas of the ontology relevant to
Parkinson’s Disease, such as vesicle trafficking, regulation of neuron death,
mitophagy etc.
•  Housing these annotations in the GO database will allow researchers to find out
more about their gene of interest, search for common processes within a gene list,
or perform more complex queries on their data set. Our annotation efforts will
therefore improve the analysis of high-throughput datasets, which rely on large
numbers of high-quality annotations for correct interpretation.
ParkinsonsUK-UCL
denotes GO terms
assigned in this
project
•  Annotation Priorities: Our primary focus is human, but we will also capture
information from model organisms including fly and mouse. Our initial annotation
targets include:
Each GO term has a unique ID, name and
definition. A GO term may contain one or more
synonyms to aid searching.
•  Parkinson’s risk genes: compiled from PDGene (database for Parkinson’s
Disease genetic association studies) and reviews on Parkinson’s Disease.
•  Interactors of risk genes: In collaboration with the IntAct Parkinson’s project
funded by the MJ Fox Foundation, we are initially prioritising interactors of
three proteins: LRRK2, α-SYNUCLEIN (SNCA) and TAU (MAPT).
Figure 2: Anatomy of an annotation: a subset of biological process GO annotations for
human PARK7 (PARKIN-7, DJ-1). Displayed in the EBI GO browser (www.ebi.ac.uk/QuickGO).
•  Processes that are often disrupted in cases of Parkinson’s: In
consultation with UCL researchers, we have identified 12 processes that are
of great interest in Parkinson’s research.
How YOU can help
Further Reading
•  We are keen to hear from you about the genes and processes YOU think we should
be annotating. Please email rebecca.foulger@ucl.ac.uk or p.denny@ucl.ac.uk.
•  Ten quick tips for using the Gene Ontology. Blake J.A. PLoS Comput Biol. Nov;
•  Search the GO annotations associated with your favourite Parkinson’s gene - let us
know if you think any annotations are missing.
•  The Gene Ontology: enhancements for 2011. The Gene Ontology Consortium. Nucleic
•  Send us your Parkinson’s-relevant papers to be annotated.
9(11):e1003343 (2013). PMID 24244145
Acids Res. 40, D559-564 (2012). PMID 22102568
•  The IntAct molecular interaction database in 2012. Kerrien et al. Nucleic Acids Res.
40, D841-846 (2012). PMID 22121220
www.ucl.ac.uk/functional-gene-annotation/neurological
www.geneontology.org
The Parkinson’s UK annotation
project is funded by Parkinson’s UK,
grant G-1307. Project members are
part of the GO Consortium.