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

Journal: Neuron
PMID:

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).

Authors

  • Frank Koopmans
    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.
  • Pim van Nierop
    Department of Molecular and Cellular Neurobiology, CNCR, VU University and UMC Amsterdam, 1081 HV Amsterdam, the Netherlands.
  • Maria Andres-Alonso
    RG Neuroplasticity, Leibniz Institute for Neurobiology, 39118 Magdeburg, Germany; Leibniz Group "Dendritic Organelles and Synaptic Function," ZMNH, University MC, Hamburg, 20251, Germany.
  • Andrea Byrnes
    Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Tony Cijsouw
    Department of Neuroscience, Tufts University School of Medicine, Boston, MA 02111, USA.
  • Marcelo P Coba
    Zilkha Neurogenetic Institute and Department of Psychiatry and Behavioral Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA 90333, USA.
  • L Niels Cornelisse
    Department of Functional Genomics, CNCR, VU University and UMC Amsterdam, 1081 HV Amsterdam, the Netherlands.
  • Ryan J Farrell
    Department of Biochemistry, Weill Cornell Medicine, New York, NY 10065, USA.
  • Hana L Goldschmidt
    Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Daniel P Howrigan
    Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Natasha K Hussain
    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.
  • Cordelia Imig
    Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany.
  • Arthur P H de Jong
    Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
  • Hwajin Jung
    Center for Synaptic Brain Dysfunctions, IBS, and Department of Biological Sciences, KAIST, Daejeon 34141, South Korea.
  • Mahdokht Kohansalnodehi
    Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany.
  • Barbara Kramarz
    Institute of Cardiovascular Science, University College London, London WC1E 6JF, United Kingdom.
  • Noa Lipstein
    Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany.
  • Ruth C Lovering
    Centre for Cardiovascular Genetics, Institute of Cardiovascular Science, University College London, Rayne Building, 5 University Street, London, WC1E 6JF, UK. r.lovering@ucl.ac.uk.
  • Harold MacGillavry
    Cell Biology, Department of Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, the Netherlands.
  • Vittoria Mariano
    Department of Fundamental Neurosciences, University of Lausanne, 1006 Lausanne, Switzerland; Department of Biomedicine and Prevention, University of Rome Tor Vergata, 00133 Rome, Italy.
  • Huaiyu Mi
    Division of Bioinformatics, Department of Preventive Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA, USA and.
  • Momchil Ninov
    Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany.
  • David Osumi-Sutherland
    European Molecular Biology Laboratory, European Bioinformatics Institute, Hinxton, Cambridge, CB10 1SD, UK.
  • Rainer Pielot
    Leibniz Institute for Neurobiology, CBBS and Medical Faculty, Otto von Guericke University, 39120 Magdeburg, Germany.
  • Karl-Heinz Smalla
    Leibniz Institute for Neurobiology, CBBS and Medical Faculty, Otto von Guericke University, 39120 Magdeburg, Germany.
  • Haiming Tang
    Division of Bioinformatics, Department of Preventive Medicine, University of Southern California, Los Angeles, CA, USA.
  • Katherine Tashman
    Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Ruud F G Toonen
    Department of Functional Genomics, CNCR, VU University and UMC Amsterdam, 1081 HV Amsterdam, the Netherlands.
  • Chiara Verpelli
    CNR Neuroscience Institute Milan and Department of Biotechnology and Translational Medicine, University of Milan, 20129 Milan, Italy.
  • Rita Reig-Viader
    Molecular Physiology of the Synapse Laboratory, Biomedical Research Institute Sant Pau, 08025 Barcelona, Spain; Universitat Autònoma de Barcelona, 08193 Bellaterra, Cerdanyola del Vallès, Spain.
  • Kyoko Watanabe
    Drug Metabolism and Pharmacokinetics Research Laboratories, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo, 140-8710, Japan.
  • Jan van Weering
    Department of Functional Genomics, CNCR, VU University and UMC Amsterdam, 1081 HV Amsterdam, the Netherlands.
  • Tilmann Achsel
    Department of Fundamental Neurosciences, University of Lausanne, 1006 Lausanne, Switzerland; Department of Biomedicine and Prevention, University of Rome Tor Vergata, 00133 Rome, Italy.
  • Ghazaleh Ashrafi
    Department of Biochemistry, Weill Cornell Medicine, New York, NY 10065, USA.
  • Nimra Asi
    Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Tyler C Brown
    Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Pietro De Camilli
    Departments of Neuroscience and Cell Biology, HHMI, Kavli Institute for Neuroscience, Yale University School of Medicine, 295 Congress Avenue, New Haven, CT 06510, USA.
  • Marc Feuermann
    Swiss-Prot group.
  • Rebecca E Foulger
    From the Institute of Cardiovascular Science (R.C.L., V.K.K., R.E.F., N.H.C., R.P.H., P.J.T., P.D.L., P.M.E., L.C.) and Metabolism and Experimental Therapeutics, Division of Medicine (R.B.), University College London, United Kingdom; European Bioinformatics Institute (EMBL-EBI), European Molecular Biology Laboratory, Hinxton, United Kingdom (P.R., D.O.-S.); Gene Ontology Consortium (P.R., T.Z.B., D.O.-S., J.A.B., D.P.H.); The Zebrafish Model Organism Database, University of Oregon, Eugene (D.G.H.); Rat Genome Database, Human Molecular Genetics Center, Medical College of Wisconsin, Milwaukee (S.J.F.L.); Arabidopsis Information Resource, Phoenix Bioinformatics, Fremont, CA (T.Z.B.); FlyBase, University of Cambridge, United Kingdom (S.T.); Mouse Genome Informatics, The Jackson Laboratory, Bar Harbor, ME (J.A.B., D.P.H.); Oxbridge BHF Centre of Regenerative Medicine, Department of Physiology, Anatomy and Genetics, University of Oxford, United Kingdom (P.R.R.); and William Harvey Heart Centre, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, United Kingdom (A.T.).
  • Pascale Gaudet
    Department of Ecology and Evolution, University of Lausanne, 1015 Lausanne, Switzerland, SIB Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland, Department of Microbiology and Immunology and Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore MD, USA, SIB Swiss Institute of Bioinformatics, 1 Rue Michel Servet, 1211 Geneva, Switzerland, Department of Medicine and Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore MD, USA, Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA 94158, USA, School of Information, University of South Florida, Tampa, FL, 33647, USA, Genomics Division, Lawrence Berkeley National Lab, 1 Cyclotron Rd., Berkeley, 94720 CA USA, European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK, Swiss-Prot Group, SIB Swiss Institute of Bioinformatics, Centre Medical Universitaire, Geneva, Switzerland, ETH Zurich, Department of Computer Science, Universitätstr. 19, 8092 Zürich, Switzerland, SIB Swiss Institute of Bioinformatics, Universitätstr. 6, 8092 Zürich, Switzerland and University College London, Gower St, London WC1E 6BT, UK.
  • Anoushka Joglekar
    Brain and Mind Research Institute and Center for Neurogenetics, Weill Cornell Medicine, New York, NY, USA.
  • Alexandros Kanellopoulos
    Department of Fundamental Neurosciences, University of Lausanne, 1006 Lausanne, Switzerland; Department of Biomedicine and Prevention, University of Rome Tor Vergata, 00133 Rome, Italy.
  • Robert Malenka
    Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305, USA.
  • Roger A Nicoll
    Departments of Cellular and Molecular Pharmacology and Physiology, University of California, San Francisco, San Francisco, CA 94158, USA.
  • Camila Pulido
    Department of Biochemistry, Weill Cornell Medicine, New York, NY 10065, USA.
  • Jaime de Juan-Sanz
    Department of Biochemistry, Weill Cornell Medicine, New York, NY 10065, USA.
  • Morgan Sheng
    Department of Neuroscience, Genentech, South San Francisco, CA 94080, USA.
  • Thomas C Südhof
    Department of Molecular and Cellular Physiology, Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.
  • Hagen U Tilgner
    Brain and Mind Research Institute and Center for Neurogenetics, Weill Cornell Medicine, New York, NY, USA.
  • Claudia Bagni
    Department of Fundamental Neurosciences, University of Lausanne, 1006 Lausanne, Switzerland; Department of Biomedicine and Prevention, University of Rome Tor Vergata, 00133 Rome, Italy.
  • Àlex Bayés
    Molecular Physiology of the Synapse Laboratory, Biomedical Research Institute Sant Pau, 08025 Barcelona, Spain; Universitat Autònoma de Barcelona, 08193 Bellaterra, Cerdanyola del Vallès, Spain.
  • Thomas Biederer
    Department of Neuroscience, Tufts University School of Medicine, Boston, MA 02111, USA.
  • Nils Brose
    Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany.
  • John Jia En Chua
    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.
  • Daniela C Dieterich
    Leibniz Institute for Neurobiology, CBBS and Medical Faculty, Otto von Guericke University, 39120 Magdeburg, Germany.
  • Eckart D Gundelfinger
    Leibniz Institute for Neurobiology, CBBS and Medical Faculty, Otto von Guericke University, 39120 Magdeburg, Germany.
  • Casper Hoogenraad
    Cell Biology, Department of Biology, Faculty of Science, Utrecht University, 3584 CH Utrecht, the Netherlands.
  • Richard L Huganir
    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.
  • Reinhard Jahn
    Department of Neurobiology, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany.
  • Pascal S Kaeser
    Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA.
  • Eunjoon Kim
    Center for Synaptic Brain Dysfunctions, IBS, and Department of Biological Sciences, KAIST, Daejeon 34141, South Korea.
  • Michael R Kreutz
    RG Neuroplasticity, Leibniz Institute for Neurobiology, 39118 Magdeburg, Germany; Leibniz Group "Dendritic Organelles and Synaptic Function," ZMNH, University MC, Hamburg, 20251, Germany.
  • Peter S McPherson
    Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, QC H3A 2B4, Canada.
  • Ben M Neale
    Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Vincent O'Connor
    Biological Sciences, University of Southampton, Southampton SO17 1BJ, UK.
  • Danielle Posthuma
    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.
  • Timothy A Ryan
    Department of Biochemistry, Weill Cornell Medicine, New York, NY 10065, USA.
  • Carlo Sala
    CNR Neuroscience Institute Milan and Department of Biotechnology and Translational Medicine, University of Milan, 20129 Milan, Italy.
  • Guoping Feng
    McGovern Institute for Brain Research, Massachusetts Institute of Technology, 43 Vassar Street, Cambridge, Massachusetts 02139, USA.
  • Steven E Hyman
    Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Paul D Thomas
    Division of Bioinformatics, Department of Preventive Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA, USA and.
  • August B Smit
    Department of Molecular and Cellular Neurobiology, CNCR, VU University and UMC Amsterdam, 1081 HV Amsterdam, the Netherlands. Electronic address: guus.smit@cncr.vu.nl.
  • Matthijs Verhage
    Department of Functional Genomics, CNCR, VU University and UMC Amsterdam, 1081 HV Amsterdam, the Netherlands. Electronic address: matthijs@cncr.vu.nl.