Research interests

Mouse Gene Expression Databases

The Gene Expression Database (GXD) captures and integrates mouse expression data generated by biomedical researchers worldwide, with a particular emphasis on mouse development. Data are acquired from the literature and via electronic data submissions from conventional laboratories and large-scale data providers, converted into standardized formats, and made freely and widely accessible to complex biological queries. By combining different types of expression data, and by adding new data on a daily basis, GXD provides increasingly complete information about expression profiles of transcripts and proteins in wild-type and mutant mice. Expression patterns from assays with differing spatial resolution are recorded in a consistent and integrated manner by using the hierarchically structured Anatomical Dictionary of Mouse Development built by our collaborators from the Edinburgh 3D Atlas and Gene Expression (EMAGE) project. GXD places the gene expression data in the larger biological context by interconnecting with many other data and resources. We are part of the Gene Ontology Consortium, which classifies genes and their products with regard to biological processes, molecular functions, and cellular components (see Blake report in this volume). Further, we work closely with the other Mouse Genome Informatics (MGI) projects (see Janan Eppig, Blake, and Bult reports in this volume) to provide the community with integrated access to genotypic, expression, and phenotypic data, and we supply links to many external resources such as PubMed, Online Mendelian Inheritance in Man (OMIM), National Center for Biotechnology Information (NCBI) EntrezGene, sequence databases, and databases from other species. GXD is available through the MGI web site or directly at http://www.informatics.jax.org/menus/expression_menu.shtml.

As a first step in the literature annotation process, we index all newly published articles documenting endogenous gene expression during mouse development with regard to authors, journals, gene(s) and embryonic age(s) analyzed, and expression assays used. This information is then immediately made available in searchable form via the Gene Expression Literature Index. We continually update the index. It covers, to the best of our knowledge, all relevant publications from 1993 to the present for all pertinent journals and 1990 to the present for major developmental journals. As of February 23, 2005, the index contained 42,088 entries, covering 10,367 references and expression information for 7,037 genes. Thus, the Gene Expression Literature Index provides a powerful tool to quickly locate specific types of expression information in the literature.

The next step is to record and make available detailed expression data from RNA in situ, immunohistochemistry, Northern blot, Western blot, RT-PCR, and RNAase protection experiments. This applies to data from the literature and to data obtained via electronic data submissions. This year, the amount of detailed expression data in GXD increased enormously, again, due to focusing our literature curation effort on publications with new genes and/or high GXD-relevant data content, and incorporating data from large-scale RNA in situ hybridization studies. As of February 2005, GXD contained standardized annotations for 18,529 expression assays that provide 196,500 expression results for 5,433 genes, together with almost 18,000 images of original expression data. GXD captures data that are biologically very complex. A large proportion of the data is from RNA in situ hybridization and immunohistochemistry experiments, many of which include data from mutant mice. Our Edinburgh colleagues continued to map two-dimensional in situ image data annotated by GXD into their 3D atlas. This is a first step toward integrating our respective databases to generate the Mouse Gene Expression Information Resource, which will combine text-based and 3D graphical methods for storing and analyzing gene expression data.

Mouse cDNA and EST data are other types of expression data stored in GXD. In collaboration with the Mouse Genome Database (MGD) we have, this year, incorporated all cDNA clone and sequence data from the I.M.A.G.E. consortium, the NIA sets, and the Mammalian Genome Collection (MGC). The source information for all of the cDNA libraries, such as information about strain, tissue, cell line, and sex, was mapped to our controlled vocabularies by coordinated automatic and manual processes. Likewise, clone records were associated with genes in GXD/MGI via manual curation and computational analysis of sequence associations. GXD is now current with regard to mouse cDNA and EST data. As of February 2005, the database includes data from 1,663,678 cDNA clones that are associated with 27,384 genes/genetic markers. The integration of all of these data enables comprehensive expression-related queries based on cDNA source information.

We continued our work on the Adult Mouse Anatomical Dictionary, which was built by the GXD project as a logical extension of the developmental dictionary. The ontology represents the anatomy both from the spatial and the systems perspective. It can, therefore, be used to describe expression patterns in the adult mouse as well as other data that relate to anatomy, such as phenotypic data, in standardized and integrated ways. Our work in this area led to two new collaborations. As part of the Standards and Ontologies for Functional Genomics (SOFG) effort, we participated in the development of the Standard Anatomical Entry List (SAEL). This is a brief list of anatomical terms of sufficient resolution to describe, for example, most mouse and human tissue samples studied in microarray experiments. In addition, the SAEL serves as a common entry point to more comprehensive mouse and human anatomical resources, such as the Adult Mouse Anatomical Dictionary. As part of the cancer Biomedical Informatics Grid (caBIG) effort, we have begun a collaboration with the National Cancer Institute (NCI) to establish mappings between the Adult Mouse Anatomy and the Adult Human Anatomy represented in the NCI Thesaurus. These mappings will enable a close integration of pre-clinical (mouse) and clinical (human) data pertinent to cancer and other human diseases and thus facilitate and accelerate cancer research.

We also completed the implementation of a laboratory database in support of a study funded by the National Heart, Lung, and Blood Institute that uses rodent models to gain insights into the molecular basis of human heart, lung, blood and sleep disorders by correlating microarray gene expression data with genetic, phenotypic, and physiological data (see Churchill report in this volume). The database captures pertinent data on animals, tissues, and RNA samples in standardized formats and provides adequate links to external resources. The study was a collaborative project with Dr. John Quackenbush from The Institute for Genomic Research (TIGR).

Publications

• The FANTOM Consortium and RIKEN Genome Exploration Research Group and Genome Science Group. 2005. The Transcriptional Landscape of the Mammalian Genome. Science 309:1559-1563.
• Hayamizu TF, Mangan M, Corradi JP and Ringwald M. 2005. The Adult Mouse Anatomical Dictionary: a tool for annotating and integrating data. Genome Biology 6:R29.
• Harris MA, Clark J, Ireland A, Lomax J, Ashburner M, Foulger R, et al. 2004 The Gene Ontolody (GO) database and informatics resource. Nucleic Acids res 32:D268-261.
• Ball C, Brazma A, Causton H, Chervitz S, Edgar R, Hingamp P, Matese JC, Parkinson H, Quackenbush J, Ringwald M, Sansone SA, Sherlock G, Spellman P, Stoeckert C, Tateno Y, Taylor R, White J, Winegarden N. 2004. Standards for microarray data: an open letter. Environ Health Perspect 112(12):A666-7.
• The Gene Ontology Consortium. 2004. The Gene Ontology (GO) Database and Informatics Resource. Nucleic Acids Research 32:D258-D261.
• Ball CA, Brazma A, Causton H, Chervitz S, Edgar R, Hingamp P, Matese JC, Parkinson H, Quackenbush J, Ringwald M, Sansone SA, Sherlock G, Spellman P, Stoeckert C, Tateno Y, Taylor R, White J, Winegarden N. 2004. Submission of microarray data to public repositories. PLoS Biol 2(9):E317.
• Richardson JE, Kadin JA, Blake JA, Bult CJ, Eppig JT, Ringwald M, and the Mouse Genome Informatics Group. 2004. From sipping on a straw to drinking from a fire hose; data integration in a public genome database. Proceedings of the 20th IEEE International Conference on Data Engineering, Boston MA, March 2004, pp 795-798.
• Hill DP, Begley DA, Finger JH, Hayamizu TF, McCright IJ, Smith CM, Beal JS, Corbani LE, Blake JA, Eppig JT, Kadin JA, Richardson JF and Ringwald M. 2004. The Mouse Genome Database(GXD):updates and enhancements. Nucleic Acids Res. 32:D568-D571.
• Balderelli RM, Hill DP, Blake JA, Adachi J, Furano M, Bradt D, Corbani LE, Cousins S, Frazer KS, Qi D, Yang L, Ramachandran S, Reed D, Zhu Y, Kasukawa T, Ringwald M King BL, Maltais LJ, McKenzie LM, Schriml LM, Maglott D, Church DM, Pruitt K, Eppig JT, Richardson JE, Kadin JA, Bult CJ. 2003. Connecting sequence and biology in the laboratory mouse. Genome Res. 13:1505-19.
• Begley DA, Ringwald M. 2002. Electronic tools to manage gene expression data. Trends Genet 18:108-110.
• Hill DP, Blake JA, Richardson JE, Ringwald M. 2002. Extension and Integration of the Gene Ontology (GO): Combining GO vocabularies with external vocabularies. Genome Res 12:1982-1991.
• The FANTOM Consortium and the RIKEN Genome Exploration Research Group Phase I and 2 Team. 2002. Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNAs. Nature 420:563-573.
• Ringwald M. 2002. The Mouse Gene Expression Database (GXD). In: Analyzing Gene Expression, Lorkowski S, Cullen P, [eds], Wiley-VCH.

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