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Neuron. 2019 Jul 17;103(2):217-234.e4. doi: 10.1016/j.neuron.2019.05.002. Epub 2019 Jun 3.

SynGO: An Evidence-Based, Expert-Curated Knowledge Base for the Synapse.

Author information

1
Department of Functional Genomics, CNCR, VU University and UMC Amsterdam, 1081 HV Amsterdam, the Netherlands; Department of Molecular and Cellular Neurobiology, CNCR, VU University and UMC Amsterdam, 1081 HV Amsterdam, the Netherlands.
2
Department of Molecular and Cellular Neurobiology, CNCR, VU University and UMC Amsterdam, 1081 HV Amsterdam, the Netherlands.
3
RG Neuroplasticity, Leibniz Institute for Neurobiology, 39118 Magdeburg, Germany; Leibniz Group "Dendritic Organelles and Synaptic Function," ZMNH, University MC, Hamburg, 20251, Germany.
4
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
5
Department of Neuroscience, Tufts University School of Medicine, Boston, MA 02111, USA.
6
Zilkha Neurogenetic Institute and Department of Psychiatry and Behavioral Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA 90333, USA.
7
Department of Functional Genomics, CNCR, VU University and UMC Amsterdam, 1081 HV Amsterdam, the Netherlands.
8
Department of Biochemistry, Weill Cornell Medicine, New York, NY 10065, USA.
9
Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
10
Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Kavli Neuroscience Discovery Institute, Johns Hopkins University, Baltimore, MD 21205, USA.
11
Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany.
12
Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
13
Center for Synaptic Brain Dysfunctions, IBS, and Department of Biological Sciences, KAIST, Daejeon 34141, South Korea.
14
Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany.
15
Functional Gene Annotation, Institute of Cardiovascular Science, UCL, London WC1E 6JF, UK.
16
Cell Biology, Department of Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, the Netherlands.
17
Department of Fundamental Neurosciences, University of Lausanne, 1006 Lausanne, Switzerland; Department of Biomedicine and Prevention, University of Rome Tor Vergata, 00133 Rome, Italy.
18
Division of Bioinformatics, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
19
European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Cambridge CB10 1SD, UK.
20
Leibniz Institute for Neurobiology, CBBS and Medical Faculty, Otto von Guericke University, 39120 Magdeburg, Germany.
21
CNR Neuroscience Institute Milan and Department of Biotechnology and Translational Medicine, University of Milan, 20129 Milan, Italy.
22
Molecular Physiology of the Synapse Laboratory, Biomedical Research Institute Sant Pau, 08025 Barcelona, Spain; Universitat Autònoma de Barcelona, 08193 Bellaterra, Cerdanyola del Vallès, Spain.
23
Department Complex Trait Genetics, CNCR, Neuroscience Campus Amsterdam, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, the Netherlands; Department of Clinical Genetics, UMC Amsterdam, 1081 HV Amsterdam, the Netherlands.
24
Departments of Neuroscience and Cell Biology, HHMI, Kavli Institute for Neuroscience, Yale University School of Medicine, 295 Congress Avenue, New Haven, CT 06510, USA.
25
SIB Swiss Institute of Bioinformatics, Centre Medical Universitaire, 1 rue Michel Servet, 1211 Geneva 4, Switzerland.
26
Brain and Mind Research Institute and Center for Neurogenetics, Weill Cornell Medicine, New York, NY, USA.
27
Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA.
28
Departments of Cellular and Molecular Pharmacology and Physiology, University of California, San Francisco, San Francisco, CA 94158, USA.
29
Department of Neuroscience, Genentech, South San Francisco, CA 94080, USA.
30
Department of Molecular and Cellular Physiology, Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
31
Department of Physiology, Yong Loo Lin School of Medicine and Neurobiology/Ageing Program, Life Sciences Institute, National University of Singapore and Institute of Molecular and Cell Biology, A(∗)STAR, Singapore, Singapore.
32
Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, QC H3A 2B4, Canada.
33
Biological Sciences, University of Southampton, Southampton SO17 1BJ, UK.
34
Department of Molecular and Cellular Neurobiology, CNCR, VU University and UMC Amsterdam, 1081 HV Amsterdam, the Netherlands. Electronic address: guus.smit@cncr.vu.nl.
35
Department of Functional Genomics, CNCR, VU University and UMC Amsterdam, 1081 HV Amsterdam, the Netherlands. Electronic address: matthijs@cncr.vu.nl.

Abstract

Synapses are fundamental information-processing units of the brain, and synaptic dysregulation is central to many brain disorders ("synaptopathies"). However, systematic annotation of synaptic genes and ontology of synaptic processes are currently lacking. We established SynGO, an interactive knowledge base that accumulates available research about synapse biology using Gene Ontology (GO) annotations to novel ontology terms: 87 synaptic locations and 179 synaptic processes. SynGO annotations are exclusively based on published, expert-curated evidence. Using 2,922 annotations for 1,112 genes, we show that synaptic genes are exceptionally well conserved and less tolerant to mutations than other genes. Many SynGO terms are significantly overrepresented among gene variations associated with intelligence, educational attainment, ADHD, autism, and bipolar disorder and among de novo variants associated with neurodevelopmental disorders, including schizophrenia. SynGO is a public, universal reference for synapse research and an online analysis platform for interpretation of large-scale -omics data (https://syngoportal.org and http://geneontology.org).

KEYWORDS:

Gene Ontology; enrichment study; gene annotation; gene set analysis; synapse; synaptic plasticity; synaptic proteome network; synaptome; synaptopathies

PMID:
31171447
PMCID:
PMC6764089
[Available on 2020-07-17]
DOI:
10.1016/j.neuron.2019.05.002
[Indexed for MEDLINE]

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