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

F. Koopmans, Pim van Nierop, M. Andres-Alonso, Andrea Byrnes, Tony Cijsouw, Marcelo P. Coba, L. Niels Cornelisse, Ryan J. Farrell, Hana L. Goldschmidt, Daniel P. Howrigan, Natasha K. Hussain, Cordelia Imig, Arthur P.H. de Jong, Hwajin Jung, Mahdokht Kohansalnodehi, Barbara Kramarz, Noa Lipstein, Ruth C. Lovering, Harold MacGillavry, Vittoria MarianoHuaiyu Mi, Momchil Ninov, D. Osumi-Sutherland, Rainer Pielot, Karl Heinz Smalla, Haiming Tang, Katherine Tashman, Ruud F.G. Toonen, Chiara Verpelli, Rita Reig-Viader, K. Watanabe, Jan van Weering, Tilmann Achsel, Ghazaleh Ashrafi, N. Asi, Tyler C. Brown, Pietro De Camilli, Marc Feuermann, Rebecca E. Foulger, Pascale Gaudet, Anoushka Joglekar, Alexandros Kanellopoulos, Robert Malenka, Roger A. Nicoll, Camila Pulido, J. de Juan-Sanz, Morgan Sheng, Thomas C. Südhof, Hagen U. Tilgner, Claudia Bagni, Àlex Bayés, Thomas Biederer, Nils Brose, John Jia En Chua, Daniela C. Dieterich, Eckart D. Gundelfinger, Casper Hoogenraad, Richard L. Huganir, Reinhard Jahn, Pascal S. Kaeser, Eunjoon Kim, Michael R. Kreutz, Peter S. McPherson, B. M. Neale, Vincent O'Connor, Danielle Posthuma, Timothy A. Ryan, C. Sala, Guoping Feng, Steven E. Hyman, Paul D. Thomas, August B. Smit, Matthijs Verhage

Research output: Contribution to journalArticleAcademicpeer-review

346 Citations (Scopus)

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). The SynGO consortium presents a framework to annotate synaptic protein locations and functions and annotations for 1,112 synaptic genes based on published experimental evidence. SynGO reports exceptional features and disease associations for synaptic genes and provides an online data analysis platform.

Original languageEnglish
Pages (from-to)217-234.e4
Number of pages22
JournalNeuron
Volume103
Issue number2
Early online date3 Jun 2019
DOIs
Publication statusPublished - 17 Jul 2019

Keywords

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

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