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

2019; Cell Press; Volume: 103; Issue: 2 Linguagem: Inglês

10.1016/j.neuron.2019.05.002

1097-4199

Frank Koopmans, Pim van Nierop, Maria Andres‐Alonso, Andrea Byrnes, Tony Cijsouw, Marcelo P. Coba, L. Niels Cornelisse, Ryan Farrell, Hana L. Goldschmidt, Daniel P. Howrigan, Natasha K. Hussain, Cordelia Imig, Arthur P.H. de Jong, Hwajin Jung, Mahdokht Kohansal-Nodehi, Barbara Kramarz, Noa Lipstein, Ruth C. Lovering, Harold D. MacGillavry, Vittoria Mariano, Huaiyu Mi, Momchil Ninov, David Osumi-Sutherland, Rainer Pielot, Karl‐Heinz Smalla, Haiming Tang, Katherine Tashman, Ruud F. Toonen, Chiara Verpelli, Rita Reig‐Viader, Kyoko Watanabe, Jan R.T. van Weering, Tilmann Achsel, Ghazaleh Ashrafi, Nimra Asi, Tyler C. Brown, Pietro De Camilli, Marc Feuermann, Rebecca E. Foulger, Pascale Gaudet, Anoushka Joglekar, Alexandros K. Kanellopoulos, Robert Malenka, Roger A. Nicoll, Camila Pulido, Jaime de Juan‐Sanz, Morgan Sheng, Thomas C. Südhof, Hagen Tilgner, Claudia Bagni, Àlex Bayés, Thomas Biederer, Nils Brose, John Jia En Chua, Daniela C. Dieterich, Eckart D. Gundelfinger, Casper C. Hoogenraad, Richard L. Huganir, Reinhard Jahn, Pascal S. Kaeser, Eunjoon Kim, Michael R. Kreutz, Peter S. McPherson, Ben Neale, Vincent O’Connor, Daniëlle Posthuma, Timothy A. Ryan, Carlo Sala, Guoping Feng, Steven E. Hyman, Paul D. Thomas, August B. Smit, Matthijs Verhage,

Machine Learning in Bioinformatics

Summary 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).