D848 Nucleic Acids Research, 2009, Vol. 37, Database issue Representation of synaptic protein complexes and organelles Transcript and protein expression resources The protein products of nervous system genes are far from evenly distributed at nerve terminals or synapses. Rather, they are integrated into large macromolecular protein complexes by scaﬀolding proteins, producing units that have distinct functional roles which create the ability of molecules to couple via adaptors activating various cell- signalling pathways (12). To capture this structural and organizational information in G2Cdb, genes whose pro- tein products are associated may be grouped into one or more gene lists. Prime examples include the two glutamate receptor complexes, the NMDA receptor complex (NRC/ MASC) and the AMPA receptor complex (ARC), both of which are key receptor complexes in synaptic transmission and synaptic plasticity at the post-synaptic membrane (1–2). A further example is the clathrin-coated vesicle containing proteins mediating receptor endocytosis (13). Towards integrating information on the function, inter- actions and phylogeny of individual proteins within the NRC/MASC complex, we previously probed its organiza- tion and developed a model of its function using a combi- nation of annotation, network and statistical approaches (14). We proposed a modular network with 13 distinct subcomponents with distributed functionality that could explain many of the features of synaptic signalling. To facilitate use of our prior analysis and to allow for expan- sion, we added the gene lists in G2Cdb for the 13 subcom- ponents of the NRC/MASC complex. External genome and molecular resources Links were established for each G2Cdb gene to publicly available genome and molecular resources. These include Ensembl (15), Vega (16), UniProt (11), Entrez Gene (17), GeneCards (18) and OMIM (19) and PubMed (20; see Table 2 for the full list). We used mapping information from Ensembl and/or the approved gene symbols from the various databases as a starting point for the cross- referencing. Cases of ambiguous or absent mapping were manually resolved using the resources’ respective websites before acceptance. Knowledge of the anatomical location and level of a pro- tein expression (distribution) proﬁle may be vital when trying to predict or interpret a phenotype in an animal created by ablating a gene, or while attempting to eluci- date the role of a gene product in a particular behaviour. We have mined the plethora of publicly available gene and protein expression resources for this valuable infor- mation. For example, through collaboration with the Allen Brain Institute, we provide the Allen Brain Atlas (21) data links to their database of gene expression pat- terns in the mouse brain. Other mouse gene expression resources were mined by automated means (BGEM, GenePaint, GENSAT, EMAGE; 22–25). Links to human protein expression proﬁles are provided for the Human Protein Atlas (26). Using automated cross- referencing these gene and protein expression links are regularly updated, maintaining synchronization with these external resources. Text-mining and human curation of published literature Curated databases containing published literature provide an invaluable tool to researchers by organizing and pre- senting disparate information in a systematic and accessi- ble manner. In the ﬁeld of synaptic signalling, functional studies have centred on the cellular mechanisms and behavioural roles of synaptic plasticity In order to optimize the arduous task of performing an extensive literature survey in areas where there are many hundreds of papers published each year, we deployed a bespoke text-mining system (described in refs 5 and 27). Brieﬂy, we pre-processed and indexed a local copy of Pubmed using Lucene (28). We then implemented a basic language classiﬁer using the regular expression capabilities of Perl to extract and rank-order abstracts with likely terms, e.g. ‘interacts with’ or ‘long term potentiation’. The resulting papers were separated into two lists and then human-curated to conﬁrm both their relevance and the identity of the gene(s) investigated. For one list, we also manually extracted the experimental conditions employed for the synaptic plasticity papers Table 2. G2Cdb cross-referenced gene, genome, expression and literature resources Content Mouse and human genomic annotation Mouse and human genomic annotation Human genes and genetic phenotypes Human-curated gene structures Human gene information Mouse brain gene expression Mouse nervous system gene expression Mouse gene expression in development Mouse embryo gene expression Mouse CNS gene expression Human protein distribution Protein knowledgebase Human gene nomenclature Mouse gene nomenclature Published scientiﬁc literature Database Ensembl NCBI Entrez Gene OMIM Vega GeneCards Allen Brain Atlas BGEM EMAGE GenePaint GENSAT Human Protein Atlas UniProt HGNC MGI PubMed URL http://www.ensembl.org http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene http://www.ncbi.nlm.nih.gov/omim http://vega.sanger.ac.uk http://www.genecards.org http://www.brain-map.org http://www.stjudebgem.org http://genex.hgu.mrc.ac.uk/Emage/database http://www.genepaint.org http://www.ncbi.nlm.nih.gov/projects/gensat http://www.proteinatlas.org http://www.uniprot.org http://www.genenames.org http://www.informatics.jax.org http://www.ncbi.nlm.nih.gov/pubmed