G2Cdb: a database of the synapse.
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1
Welcome Trust Sanger Institute, United Kingdom
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2
University of Edinburgh, United Kingdom
Understanding the brain, particularly the means by which it allows organisms to successfully adapt to their environment is a huge challenge to biology, and the central focus of neuroscience. Neuroinformatics brings methods, databases and tools for integrating, searching and modelling multidisciplinary neuroscience data. The scope and complexity of the task is truly enormous, extending from the neurotransmitter receptors that act as the sensing component of chemical synapses, to developing accurate models of the brain circuitries as a whole, which in the human is estimated to be formed by as many as 1014 synapses connecting 50-100 billion neurons.
Synapses constitute the fundamental unit of computation in the brain, and it is upon these that G2Cdb focuses. Synapses not only transmit information between cells but also detect patterns of neural activity, processing this information by activating intracellular biochemical signalling pathways, regulating downstream effectors and subsequent output mechanisms. Synapses also have the ability to dynamically regulate the strength of the interconnection they form between neurons, a process known as synaptic plasticity, which is the best molecular correlate of the learning and memory processes that underlie cognition.
G2Cdb warehouses sets of genes and proteins experimentally elucidated by proteomic mass spectroscopy of signalling complexes and proteins biochemically isolated from mammalian synapse preparations. This gives an experimentally validated definition of the constituents of the mammalian synapse. In addition to experimental data obtained in house, we use automated text-mining and expert (human) curation to extract information from published neurobiological studies of synaptic signalling electrophysiology and behavior in transgenic mice. We have also surveyed the human genetics literature for associations to disease caused by mutations in synaptic genes.
We integrated these synaptic datasets 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 neurobiological models or whether mutations are associated with a human disease. We have thus linked genotype to phenotype in the area of synaptic neurobiology and human psychiatry by utilizing information from both human and mouse model organism research queryable via their genomic orthology.
G2Cdb provides a framework for future work in synapse biology and neuroinformatics. Utilising the synapse proteome datasets, a major application of G2Cdb will be in guiding the assembly of molecular networks of the synapse. These include transcriptional, protein interaction, and phosphorylation network models. Combining these with phenotypic data on specific proteins in electrophysiology and behavior from mice, and human disease information will be useful for synapse systems biology. G2Cdb allows one to make progress towards developing electronic representations of synapse architecture and function, potentially shedding light on the molecular pathogenesis of a range of human cognitive disorders including autism, mental retardation and schizophrenia.
Conference:
Neuroinformatics 2009, Pilsen, Czechia, 6 Sep - 8 Sep, 2009.
Presentation Type:
Poster Presentation
Topic:
Genomics and genetics
Citation:
Croning
MD,
Armstrong
JD and
Grant
SG
(2019). G2Cdb: a database of the synapse..
Front. Neuroinform.
Conference Abstract:
Neuroinformatics 2009.
doi: 10.3389/conf.neuro.11.2009.08.039
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Received:
21 May 2009;
Published Online:
09 May 2019.
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Correspondence:
Mike D Croning, Welcome Trust Sanger Institute, Paris, United Kingdom, mdr@sanger.ac.uk