D846–D851 Nucleic Acids Research, 2009, Vol. 37, Database issue doi:10.1093/nar/gkn700 Published online 4 November 2008 G2Cdb: the Genes to Cognition database Mike D. R. Croning 1 , Michael C. Marshall1, Peter McLaren 1 , J. Douglas Armstrong2 and Seth G. N. Grant1,* 1Genes to Cognition Programme, Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA and 2Institute for Adaptive and Neural Computation, School of Informatics, University of Edinburgh, 10 Crichton Street, Edinburgh EH8 9AB, UK Received August 15, 2008; Revised September 25, 2008; Accepted September 26, 2008 ABSTRACT Neuroscience databases linking genes, proteins, (patho)physiology, anatomy and behaviour across species will be valuable in a broad range of studies of the nervous system. G2Cdb is such a neu- roscience database aiming to present a global view of the role of synapse proteins in physiology and disease. G2Cdb warehouses sets of genes and proteins experimentally elucidated by proteomic mass spectroscopy of signalling complexes and proteins biochemically isolated from mammalian synapse preparations, giving an experimentally vali- dated definition of the constituents of the mamma- lian synapse. Using automated text-mining and expert (human) curation we have systematically extracted information from published neurobiologi- cal studies in the fields of synaptic signalling elec- trophysiology and behaviour in knockout and other transgenic mice. We have also surveyed the human genetics literature for associations to disease caused by mutations in synaptic genes. The syn- apse proteome datasets that G2Cdb provides offer a basis for future work in synapse biology and pro- vide useful information on brain diseases. They have been integrated in a such way that investigators can rapidly query whether a gene or protein is found in brain-signalling complex(es), has a phenotype in rodent models or whether mutations are associated with a human disease. G2Cdb can be freely accessed at http://www.genes2cognition.org. INTRODUCTION Synapses are the fundamental unit of computation in the brain playing key roles in information processing, behav- iour and disease. They not only transmit information between cells but also detect patterns of neural activity and process this information by activating intracellular biochemical signalling pathways, which subsequently changes the properties of the neuron. G2Cdb presents an integrated view of the role of synapses, focusing on large, high-quality datasets describing synaptic proteins and diseases of the nervous system, particularly those aﬀecting cognition. Since the year 2000, proteomic studies have increased the number of known synaptic proteins over 10-fold and provided lists of proteins that represent the draft synapse proteome (1,2 and other references therein). The synapse has diﬀerent compartments, such as the post-synaptic pro- teome (PSP), comprising 1100 proteins, and pre-synaptic vesicles with 80 proteins (3). The high degree of com- plexity was unexpected and understanding the function of individual proteins and the overall organization of the molecular networks presents a major challenge. G2Cdb aims to be the central database for warehousing data on the synaptic proteome. Other useful databases exist for molecular neuroscience of which the closest is Synapse DataBase (SynDB). G2Cdb diﬀers fundamentally from SynDB both in terms of the data content and in the way it is constructed. SynDB employs keyword and ontology-term searching of protein sequence and motif databases to provide an informatic deﬁnition of the synapse (4). In contrast, G2Cdb uses data curated from published studies of synaptic protein proﬁling to provide an experimentally validated representation of the mamma- lian synapse. Both approaches, and thus databases, are highly complementary. Building upon this proteomic deﬁnition of the synapse G2Cdb integrates mouse and human genomic annotation resources, forming the basis of a ‘molecular catalogue’ of mammalian synaptic genes. Information mined from the human genetics literature reporting associations between synaptic gene mutations and disease is included, as is our in-depth and on-going survey of the neurobiological phe- notypes observed in published studies of knockout and other transgenic mice. With the aim of presenting a global view of the role of synapses in physiology and disease, these datasets have been integrated in a gene-centric manner. The result- ing database, G2Cdb, should be of interest to all *To whom correspondence should be addressed. Tel: +44 1223 834244; Fax: +44 1223 494919; Email: sg3@sanger.ac.uk 2008 The Author(s) This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/ by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.