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 Mariano; Huaiyu 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

doi:10.1016/j.neuron.2019.05.002

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

^*Corresponding author for this work

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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 language	English
Pages (from-to)	217-234.e4
Number of pages	22
Journal	Neuron
Volume	103
Issue number	2
Early online date	3 Jun 2019
DOIs	https://doi.org/10.1016/j.neuron.2019.05.002
Publication status	Published - 17 Jul 2019

Funding

SynGO was funded by The Stanley Center for Psychiatric Research at The Broad Institute of MIT and Harvard . SynGO was built on previous efforts (synaptic parts lists) funded by the European Union ( EUROSPIN HEALTH-F2-2009-241498 and SYNSYS HEALTH-F4-2010-242167 ). A.B.P. was supported by Spanish grants BFU2012-34398 and BFU2015-69717-P (partially funded by FEDER funds of the European Union ), Ramón y Cajal fellowship RYC-2011-08391 , the European FP People Marie Curie Action career integration grant 304111 , and the CERCA Program/Generalitat de Catalunya . M.R.K. was supported by DFG CRC779 Project B08 , EU-JPND STAD , and Leibniz Foundation SAW . P.D.C. was supported by NIH NS36251 . E.D.G. and D.C.D. were supported by DFG CRC779 Project B09 . N.B. was supported by the German Federal Ministry of Education and Research ( ERA-NET Neuron Synpathy ) and an ERC advanced grant from the European Union ( SynPrime ). M.V. was supported by an ERC advanced grant from the European Union ( ERC-ADG-322966-DCVfusion ).

Funders	Funder number
National Institute of Mental Health	R01MH113349, R21MH113949, R21MH115404, R01MH115005
National Institute on Drug Abuse	P30DA018343
National Institute of Neurological Disorders and Stroke	R01NS036251, R01NS083898, R01NS103484
H2020 European Research Council
European Commission	SynPrime, ERC-ADG-322966-DCVfusion
Deutsche Forschungsgemeinschaft	CRC779 Project B09, CRC779 Project B08
Bundesministerium für Bildung und Forschung	ERA-NET Neuron Synpathy
European Regional Development Fund
Norges Idrettshøgskole

Keywords

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

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10.1016/j.neuron.2019.05.002

SynGO_An Evidence-Based, Expert-Curated Knowledge Base for the SynapseFinal published version, 3.87 MBLicence: Article 25fa Dutch Copyright Act

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Koopmans, F., van Nierop, P., Andres-Alonso, M., Byrnes, A., Cijsouw, T., Coba, M. P., Cornelisse, L. N., Farrell, R. J., Goldschmidt, H. L., Howrigan, D. P., Hussain, N. K., Imig, C., de Jong, A. P. H., Jung, H., Kohansalnodehi, M., Kramarz, B., Lipstein, N., Lovering, R. C., MacGillavry, H., ... Verhage, M. (2019). SynGO: An Evidence-Based, Expert-Curated Knowledge Base for the Synapse. Neuron, 103(2), 217-234.e4. https://doi.org/10.1016/j.neuron.2019.05.002

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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.",

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

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Koopmans, F, van Nierop, P, Andres-Alonso, M, Byrnes, A, Cijsouw, T, Coba, MP, Cornelisse, LN, Farrell, RJ, Goldschmidt, HL, Howrigan, DP, Hussain, NK, Imig, C, de Jong, APH, Jung, H, Kohansalnodehi, M, Kramarz, B, Lipstein, N, Lovering, RC, MacGillavry, H, Mariano, V, Mi, H, Ninov, M, Osumi-Sutherland, D, Pielot, R, Smalla, KH, Tang, H, Tashman, K, Toonen, RFG, Verpelli, C, Reig-Viader, R, Watanabe, K, van Weering, J, Achsel, T, Ashrafi, G, Asi, N, Brown, TC, De Camilli, P, Feuermann, M, Foulger, RE, Gaudet, P, Joglekar, A, Kanellopoulos, A, Malenka, R, Nicoll, RA, Pulido, C, de Juan-Sanz, J, Sheng, M, Südhof, TC, Tilgner, HU, Bagni, C, Bayés, À, Biederer, T, Brose, N, Chua, JJE, Dieterich, DC, Gundelfinger, ED, Hoogenraad, C, Huganir, RL, Jahn, R, Kaeser, PS, Kim, E, Kreutz, MR, McPherson, PS, Neale, BM, O'Connor, V, Posthuma, D, Ryan, TA, Sala, C, Feng, G, Hyman, SE, Thomas, PD, Smit, AB & Verhage, M 2019, 'SynGO: An Evidence-Based, Expert-Curated Knowledge Base for the Synapse', Neuron, vol. 103, no. 2, pp. 217-234.e4. https://doi.org/10.1016/j.neuron.2019.05.002

TY - JOUR

T1 - SynGO

T2 - An Evidence-Based, Expert-Curated Knowledge Base for the Synapse

AU - Koopmans, F.

AU - van Nierop, Pim

AU - Andres-Alonso, M.

AU - Byrnes, Andrea

AU - Cijsouw, Tony

AU - Coba, Marcelo P.

AU - Cornelisse, L. Niels

AU - Farrell, Ryan J.

AU - Goldschmidt, Hana L.

AU - Howrigan, Daniel P.

AU - Hussain, Natasha K.

AU - Imig, Cordelia

AU - de Jong, Arthur P.H.

AU - Jung, Hwajin

AU - Kohansalnodehi, Mahdokht

AU - Kramarz, Barbara

AU - Lipstein, Noa

AU - Lovering, Ruth C.

AU - MacGillavry, Harold

AU - Mariano, Vittoria

AU - Mi, Huaiyu

AU - Ninov, Momchil

AU - Osumi-Sutherland, D.

AU - Pielot, Rainer

AU - Smalla, Karl Heinz

AU - Tang, Haiming

AU - Tashman, Katherine

AU - Toonen, Ruud F.G.

AU - Verpelli, Chiara

AU - Reig-Viader, Rita

AU - Watanabe, K.

AU - van Weering, Jan

AU - Achsel, Tilmann

AU - Ashrafi, Ghazaleh

AU - Asi, N.

AU - Brown, Tyler C.

AU - De Camilli, Pietro

AU - Feuermann, Marc

AU - Foulger, Rebecca E.

AU - Gaudet, Pascale

AU - Joglekar, Anoushka

AU - Kanellopoulos, Alexandros

AU - Malenka, Robert

AU - Nicoll, Roger A.

AU - Pulido, Camila

AU - de Juan-Sanz, J.

AU - Sheng, Morgan

AU - Südhof, Thomas C.

AU - Tilgner, Hagen U.

AU - Bagni, Claudia

AU - Bayés, Àlex

AU - Biederer, Thomas

AU - Brose, Nils

AU - Chua, John Jia En

AU - Dieterich, Daniela C.

AU - Gundelfinger, Eckart D.

AU - Hoogenraad, Casper

AU - Huganir, Richard L.

AU - Jahn, Reinhard

AU - Kaeser, Pascal S.

AU - Kim, Eunjoon

AU - Kreutz, Michael R.

AU - McPherson, Peter S.

AU - Neale, B. M.

AU - O'Connor, Vincent

AU - Posthuma, Danielle

AU - Ryan, Timothy A.

AU - Sala, C.

AU - Feng, Guoping

AU - Hyman, Steven E.

AU - Thomas, Paul D.

AU - Smit, August B.

AU - Verhage, Matthijs

PY - 2019/7/17

Y1 - 2019/7/17

N2 - 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.

AB - 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.

KW - enrichment study

KW - gene annotation

KW - Gene Ontology

KW - gene set analysis

KW - synapse

KW - synaptic plasticity

KW - synaptic proteome network

KW - synaptome

KW - synaptopathies

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U2 - 10.1016/j.neuron.2019.05.002

DO - 10.1016/j.neuron.2019.05.002

M3 - Article

C2 - 31171447

AN - SCOPUS:85068734308

SN - 0896-6273

VL - 103

SP - 217-234.e4

JO - Neuron

JF - Neuron

IS - 2

ER -

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

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