GXD: a community resource of mouse Gene Expression Data

GXD: a community resource of mouse Gene Expression Data Constance M. Smith 0 Jacqueline H. Finger 0 Terry F. Hayamizu 0 Ingeborg J. McCright 0 Jingxia Xu 0 Janan T. Eppig 0 James A. Kadin 0 Joel E. Richardson 0 Martin Ringwald 0 0 The Jackson Laboratory , Bar Harbor, ME 04609 , USA The Gene Expression Database (GXD) is an extensive, easily searchable, and freely available database of mouse gene expression information (www.informatics. jax.org/expression.shtml). GXD was developed to foster progress toward understanding the molecular basis of human development and disease. GXD contains information about when and where genes are expressed in different tissues in the mouse, especially during the embryonic period. GXD collects different types of expression data from wild-type and mutant mice, including RNA in situ hybridization, immunohistochemistry, RT-PCR, and northern and western blot results. The GXD curators read the scientific literature and enter the expression data from those papers into the database. GXD also acquires expression data directly from researchers, including groups doing large-scale expression studies. GXD currently contains nearly 1.5 million expression results for over 13,900 genes. In addition, it has over 265,000 images of expression data, allowing users to retrieve the primary data and interpret it themselves. By being an integral part of the larger Mouse Genome Informatics (MGI) resource, GXD's expression data are combined with other genetic, functional, phenotypic, and disease-oriented data. This allows GXD to provide tools for researchers to evaluate expression data in the larger context, search by a wide variety of biologically and biomedically relevant parameters, and discover new data connections to help in the design of new experiments. Thus, GXD can provide researchers with critical insights into the functions of genes and the molecular mechanisms of development, differentiation, and disease. - Recent technological advances have made it possible to rapidly determine the sequences of individual human genomes and to correlate genetic mutations with human diseases. Evolutionarily closely related to humans, the mouse is a pivotal model system for determining the molecular mechanisms that lead from specific mutations to developmental defects and disease phenotypes. In mouse, specific constitutive and conditional mutants can be easily generated, and tissues from many different strains and mutants, as well as all developmental stages, can be obtained for gene expression analyses. These expression data can then be correlated with phenotypic and disease data to gain insights into the function of genes and the molecular mechanisms that underlie human development, differentiation, and disease. The objective of the Gene Expression Database (GXD) is to support and facilitate the studies of the molecular mechanisms that underlie developmental and disease processes. GXD systematically collects and integrates different types of expression data from wild-type and mutant mice through curation of the published literature and by collaboration with large-scale projects and makes them available to researchers in an extensive and easily searchable database (Finger et al. 2011; Smith et al. 2014a). Further, as an integral component of the larger Mouse Genome Informatics (MGI) resource, GXD combines its data with all the other genetic, genomic, function, phenotypic, and diseaserelated information in MGI, thus placing these expression data in context and making them readily accessible to many types of biologically and biomedically relevant database searches (Eppig et al. 2015; Smith et al. 2014b). The importance of recording and integrating mouse expression data and placing them in a larger biological context cannot be overstated. It is impossible for any single individual to keep abreast of all the biomedical research data that are generated yearly, let alone to memorize all these data and their connections. The ability to find results of previous experiments quickly can save investigators months of research time, both in the library and in the laboratory. In addition, GXD and MGI enable researchers to discover new data connections, thus allowing them to develop scientific hypotheses and to design new experiments. In the following paragraphs, we will discuss: the contents of GXD; how and why expression data are recorded in standardized ways; the integration of expression data with other data in MGI; and the tools provided by GXD to explore these data. GXD collects endogenous gene expression information derived from wild-type and mutant mice. It includes data from all stages of development, including postnatal development, although the main emphasis is gene expression during the embryonic period. GXD provides researchers a comprehensive survey of the embryonic expression literature, detailed expression data, and tools to examine these data. Because different types of expression assays yield different information about gene products at the RNA and protein level, GXD has been designed as a system that can integrate multiple types of expression data (Ringwald et al. 1994). GXDs emphasis has been, and continues to be, on data from RNA in situ, immunohistochemistry, knock-in reporter, RT-PCR, northern blot, and western blot experiments. Links to array and high-throughput sequencing expression data at NCBI GEO (Barrett et al. 2013) and the Expression Atlas at EMBL-EBI (Petryszak et al. 2014) are provided as well, and closer integration of these data within GXD is planned for the future. GXDs data content and acquisition efforts are unique, integrating heterogeneous expression data from disparate sources. GXD is the only database that systematically curates mouse developmental expression data from the literature. The GXD curators have read and entered the results from thousands of published papers into GXD. Additional data are acquired via electronic data submissions and through collaborations with large-scale data providers. The large-scale projects whose data are in GXD include: GenePaint (Visel et al. 2004), Eurexpress (DiezRoux et al. 2011), the Brain Gene Expression Map (BGEM; Magdaleno et al. 2006), and the GenitoUrinary Development Molecular Anatomy Project (GUDMAP; Harding et al. 2011). Thus, the data in GXD represent the results of research performed by small- and large-scale laboratories worldwide. GXD currently contains detailed expression results from almost 70,000 experiments and data for nearly 1.5 million expression results examining the expression of approximately 13,900 genes. This includes data from more than 2100 mouse mutants. In addition, it has over 265,000 images of the original data, allowing researchers to view and interpret the experiments themselves. Eighty-two percent of the data are from RNA in situ hybridization studies and 10 % from RT-PCR experiments, reflecting the detailed spatial resolution and sensitivity required in developme (...truncated)