The Mouse Gene Expression Database (GXD)

Martin Ringwald 0 Janan T. Eppig 0 Dale A. Begley 0 John P. Corradi 0 Ingeborg J. McCright 0 Terry F. Hayamizu 0 David P. Hill 0 James A. Kadin 0 Joel E. Richardson 0 0 The Jackson Laboratory , 600 Main Street, Bar Harbor, ME 04609, USA The Gene Expression Database (GXD) is a community resource of gene expression information for the laboratory mouse. By combining the different types of expression data, GXD aims to provide increasingly complete information about the expression profiles of genes in different mouse strains and mutants, thus enabling valuable insights into the molecular networks that underlie normal development and disease. GXD is integrated with the Mouse Genome Database (MGD). Extensive interconnections with sequence databases and with databases from other species, and the development and use of shared controlled vocabularies extend GXD's utility for the analysis of gene expression information. GXD is accessible through the Mouse Genome Informatics web site at http://www.informatics.jax.org/ or directly at http://www.informatics.jax.org/menus/ expression_menu.shtml. - The laboratory mouse has become a pivotal animal model in biomedical research because it is closely related to the human and readily amenable to genetic and molecular analysis. Tissues from many different mouse strains and mutants, and from all developmental and adult stages, are easily accessible for expression analysis. The different methods used to detect gene products vary in sensitivity and spatial resolution and contribute distinct and complementary expression information. The Gene Expression Database (GXD) has been designed as an open-ended system that can integrate many different types of expression data, such as RNA in situ hybridization, immunohistochemistry, northern blot, western blot, RTPCR, cDNA source and array data (15). Thus, as data accumulate, GXD can provide increasingly complete information about what transcripts and proteins are produced by what genes; where, when and in what amounts these gene products are expressed; and how their expression varies in different mouse strains and mutants. Expression patterns reported from assays with differing spatial resolution are described in standardized and integrated form using an extensive, hierarchically structured dictionary of anatomical terms for mouse development built in collaboration with our Edinburgh colleagues (6). Digitized images of original expression data are linked to the respective expression records. GXD is integrated with the Mouse Genome Database (MGD) (7) to enable a combined analysis of genotype, expression and phenotype information, and has comprehensive links to other resources, such as sequence databases (812), OMIM, MEDLINE and databases from other species. Such information places gene expression data in the larger biological and analytical context. GXD is implemented in the Sybase relational database management system. It has been available online since July 1998 and has been updated on a daily basis. Access to data is provided primarily via Web-based query forms. Users interested in direct SQL access may arrange for an SQL account by contacting MGI User support (see below). GXD and its WWW query interface have been described in more detail previously (3,4). Here, we illustrate recent enhancements of GXD from the users perspective, by taking the different query forms provided by GXD as an entry point. The Gene Expression Data index Using the GXD index, one can rapidly identify publications that contain endogenous developmental gene expression information for specific genes, for particular days of mouse development, from specific assay types or for any combination of these parameters. Additional query fields are provided for bibliographic information (authors, journals, year) and for words (text strings) that occur in the abstract of the respective articles. We continue to keep the GXD index up-to-date. All pertinent journal articles from 1993 to the present and articles from major developmental journals from 1990 to the present are indexed. As of September 28, 2000, the index includes 17 401 entries covering 5635 references and expression information for 3837 genes. The Gene Expression Data query form The Gene Expression Data query form provides access to data from RNA in situ hybridization, immunohistochemistry, northern blot, western blot, RTPCR and RNase protection experiments. Using combinations of search parameters, one can ask increasingly complex expression queries, such as: In what anatomical structures and/or at what developmental stages has a specified gene or a specified set of genes been detected/not detected? or What genes have been detected/not detected in a given tissue and/or at a particular time of development using a specified set of expression assays? Due to the hierarchical structure of the anatomical dictionary, spatial queries can include anatomical substructures or superstructures. Further, it is possible to correlate gene expression with chromosomal location, a query particularly relevant for hunting candidate genes. The query capabilities for chromosomal location have been refined. It is now possible to search for genes located on a particular chromosome, between specified loci or within a specified distance from a genetic locus. The most significant enhancement of the Gene Expression Data query form is that one can now also search for genes whose products perform a particular molecular function (e.g. transcription factor or DNA helicase); are involved in a specified biological process (e.g. apoptosis or purine metabolism); or belong to a defined cellular component (e.g. nucleus or origin recognition complex). As a member of the Gene Ontology Project (13), we participate in building shared controlled vocabularies for these three categories and in assigning pertinent terms to genes in our database. The addition of these search parameters enables important new queries such as What transcription factors are expressed in the diencephalon from day 11.515 of mouse development? or What genes involved in apoptosis have been detected in the limb? and enhances the utility of the expression data stored in GXD. The Mouse Anatomical Dictionary Browser The Mouse Anatomical Dictionary Browser has been added as a new tool to navigate through the extensive dictionary hierarchies for the different developmental stages, to locate specific anatomical structures in the hierarchies and to look up expression results associated with those structures (Fig. 1). Thus, while the Gene Expression Data query form described above enables powerful combinatorial queries (including anatomical structures), the anatomy browser lets users view gene expression data directly from the developmental anatomy perspective. It must be noted that Theiler stages 2326 have been added only recently and are still under development. So far, only limited expression data have been entered for these stages of mouse developm (...truncated)