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Mouse Genome Informatics, The Jackson Laboratory, Bar Harbor, Maine 04609
| ABSTRACT |
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| Introduction |
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Knowing about the inherent cancer phenotype of a particular mouse strain is of utmost importance for the development of new mouse models for cancer research. However, finding this information can be difficult because of the dispersed nature of the literature and inconsistencies in the nomenclature used for describing tumors in mice and designating mouse strains. In response to an NCI initiative, MTB3 , 4 was developed at The Jackson Laboratory as an electronic resource focusing on the genetics, epidemiology, and pathology of cancer in genetically defined strains of mice. The primary objective of MTB is to collect information regarding the effect of genetic background on tumorigenesis in mice. To accomplish this goal, MTB curators integrate published and unpublished data on tumor frequency or incidence, genetics, and pathology for different strains of laboratory mice. MTB is designed to aid researchers in determining the intrinsic cancer-related phenotypes of different mouse strains, reviewing patterns of mutations in specific tumors, and identifying genes that are commonly mutated across a spectrum of cancers in the mouse (11, 12, 13) .
Data Acquisition and Curation.
The main data source for MTB is the peer-reviewed scientific literature. The curation staff of the Mouse Genome Database (14)
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and MTB collaboratively review >350 journals each month. In addition, electronic searches of PubMed at the National Library of Medicine (Bethesda, MD) are performed periodically to identify recent articles describing mouse cancer models. MTB also contains unpublished information obtained from extramural contributors and routine health surveillance studies of The Jackson Laboratory mouse colonies (15)
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MTB focuses on providing the most comprehensive coverage possible of tumor pathobiology data associated with inbred strains of mice commonly used in cancer research and recently developed genetic mouse models of cancer. The latter category includes genetically engineered mice, chemically induced mutants (e.g., strains emerging from N-ethyl-N-nitrosourea mutagenesis projects), and spontaneous mutants. MTB does not contain information on tumor cell lines or preclinical trials using tumor xenograft models, because these types of data are available from other web-based resources (Table 1)
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450 queries/day. Users of the database include scientists from academic and private research institutions, as well as biotech and pharmaceutical companies.
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An overview of the cancer spectrum characteristic of inbred mouse strains can be obtained from a graphical matrix, the Tumor Frequency7
Grid (Fig. 1)
. For ease of comparison, strain families are grouped according to their genealogy (5)
. Color-coded fields indicate the highest reported frequency of spontaneous tumors in a particular organ or tissue. The Tumor Frequency Grid doubles as a query tool; a mouse-click on a colored cell returns a summary table of all of the tumor records pertinent to that particular organ or tissue in the selected strain.
The "Tumor Search" form can be used to perform custom queries. As shown in Fig. 2
, the user determines the specificity of the query depending on the number of fields selected from pull-down menus or parameters entered into text fields. This allows database users to cast a broad net (e.g., "show me all records of lymphoblastic leukemias") or to ask very specific questions (see legend to Fig. 2
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Data Presentation.
In response to a query by a user, MTB initially returns a tabular summary of all records that match the selected query terms and constraints. The number of records displayed depends on the specificity of the query. The user can then select an individual record from the summary table and retrieve a Detail Information page (Fig. 3)
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The high degree of data integration allows the user to retrieve a maximum amount of information from one query. Each tumor record is linked to frequency data, information about the genetics of the mouse strain, age of the animals at diagnosis, and a literature citation. Where applicable, MTB reports the experimental regimen (referred to as "treatment") used to promote or inhibit tumor formation. Tumor pathology data are represented by annotated histology photomicrographs that are associated with detailed captions authored by veterinary pathologists (Fig. 3)
. MTB currently contains
100 images of mouse tumors, some of which represent previously unpublished data obtained from The Jackson Laboratory mouse colonies.
Hypertext links connect MTB to other databases providing supplementary information. For instance, gene and allele symbols are hyperlinked to the Mouse Genome Database, which contains gene mapping and expression data, genomic linkage maps, phenotype descriptions, and links to orthologous genes in other mammals. If a mouse strain is available from The Jackson Laboratory or from the MMHCC,10 hyperlinks lead to strain and availability information from the JAX Mice11 database or the MMHCC Repository,12 respectively. Where appropriate, MTB provides links to tumor type-specific or strain-specific databases, such as the Biology of the Mammary Gland13 web site at the NIH, and the Transgenic Adenocarcinoma of the Mouse Prostate14 web site at Baylor College of Medicine (Houston, TX).
Pathology Data Submission.
Although expert curation of the literature is the primary data acquisition strategy, MTB also invites direct submissions of tumor pathology photomicrographs from the research community. Because most print journals impose restrictions on the acceptable number of figures per article, researchers are often forced to select only a few representative images. Consequently, much valuable pathology data remains unpublished. By providing scientists with the opportunity to contribute supplementary photomicrographs, MTB seeks to fill this gap. To facilitate the data submission process, we have implemented JaxPath, a web-based editorial tool that allows researchers to review their images and edit annotations and captions on-line. JaxPath records are password-protected and are merged into the publicly accessible database only with explicit permission from the submitting investigators. Information on the pathology data submission process and sample records can be obtained by following the JaxPath link from the MTB home page (Fig. 1)
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Future Directions.
MTB is the most extensive resource of mouse tumor pathobiology data currently available on the web (24)
. Maintaining and expanding the database through literature data curation is an integral part of The Jackson Laboratorys Mouse Genome Informatics program. The MTB information content is updated weekly. New tools are being designed for MTB to enhance the representation of quantitative trait loci mapping data, to accommodate large-scale tumor genotype and gene expression profiling data, and to include images produced with in vivo tumor imaging technologies that are being adapted to mice. Hyperlinks will connect MTB with the mouse cancer phenotype database being developed by the MMHCC. To ensure database interoperability, MTB will adopt the controlled vocabularies of diagnostic disease terms that are being evaluated by the MMHCC. Finally, MTB welcomes critical comments and suggestions from the cancer research community to improve data accuracy and user-friendliness.
| ACKNOWLEDGMENTS |
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| FOOTNOTES |
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1 Supported by grant CA89713 and in part by Cancer Core Grant CA34196 from the National Cancer Institute to The Jackson Laboratory. ![]()
2 To whom requests for reprints should be addressed, at The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609. Phone: (207) 288-6039; Fax: (207) 288-6132; E-mail: dnaf{at}informatics.jax.org ![]()
3 The abbreviations used are: MTB, Mouse Tumor Biology Database; NCI, National Cancer Institute; Trp53, transformation related protein 53; p19ARF, alternative-reading-frame protein; Cdkn2a, cyclin-dependent kinase inhibitor 2A; MMHCC, Mouse Models for Human Cancers Consortium; Apc, adenomatosis polyposis coli. ![]()
4 Internet address: http://tumor.informatics.jax.org. ![]()
5 Internet address: http://www.informatics.jax.org. ![]()
6 MTB distinguishes between males and females of a particular strain or cohort of mice to account for genetic and physiological differences between the sexes. The term cohort refers to populations of mice that were not maintained as breeding strains (e.g. F1 siblings of a particular cross), or to individual animals (e.g. chimeras, transgenic founders). ![]()
7 Tumor frequency data in MTB represent the percentage of affected animals as reported in a particular study. Tumor incidence is a population-level phenomenon that reflects the inherent tendency of a particular mouse strain to develop a specific type of tumor. ![]()
8 Internet address: http://www.informatics.jax.org/mgihome/GXD/aboutGXD.shtml. ![]()
9 Internet address: http://www.informatics.jax.org/mgihome/nomen. ![]()
10 Internet address: http://emice.nci.nih.gov. ![]()
11 Internet address: http://jaxmice.jax.org/index.shtml. ![]()
12 Internet address: http://web.ncifcrf.gov/researchresources/mmhcc/default.asp. ![]()
13 Internet address: http://mammary.nih.gov. ![]()
14 Internet address: http://www-tramp-model.cellb.bcm.tmc.edu. ![]()
Received 8/20/01. Accepted 12/21/01.
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