The MTB web site is designed to provide users with a variety of search options that accommodate a broad range of perspectives from within the cancer research community. This design allows users to search the database using a query designed to address their own particular area of interest. The following are examples of some of the types of queries that may be asked of and answered by the database.
First-time MTB users
First-time users of MTB might not be sure where to start in their exploration of the database. In this case the ‘Quick Organ/Tissue’ search form, located on the MTB home page, provides a simple introduction to the data and the interface. This search form consists of a pick list that contains an extensive vocabulary of mouse anatomical terms. Choosing one of the terms from the list and clicking on the ‘Search’ button will launch a search for records in which the organ of origin of the tumour matches the chosen term, regardless of tumour type. For example to answer the question “Do mice get tumours of the adrenal gland?” one could first search for ‘adrenal gland’. This returns over 200 records of adrenal gland tumours in mice; some are spontaneous tumours and others are those induced following some sort of treatment (chemical, hormonal or radiation). These lesions arose in a variety of strain types (inbred, hybrid, fostered, targeted mutant, chimeric and transgenic). Data provided on the results page include tumour name, organ affected, treatment type and agents (if applicable), strain name and type, tumour frequency and metastasis information as well as links to any related images (if available). Clicking on the ‘Summary’ hyperlink for a particular tumour record will display the ‘Tumor Summary’ page, which presents additional information regarding the selected tumour. These data may include information such as reproductive status of the affected mice, tumour frequency details (colony size and number of mice affected), tumour latency, pathology notes, tumour genetics and additional notes as well as links to the appropriate references.
If a researcher is interested primarily in spontaneous tumours in inbred mice, another useful option is the Tumor Frequency Grid (, Tumor Frequency Grid movie in Further information). This is a display and dynamic search tool that can be accessed by clicking on the ‘Tumor Frequency Grid’ hyperlink. The current version of the grid derives from all the current data held in MTB for spontaneous tumours in inbred mice and clicking on one of the data cells will open a ‘Tumor Results’ page as described above. The grid may be particularly useful when taking genetic background into consideration in planning the construction of a new mutant strain, choosing strains for a study of complex traits or designing other experiments.
Repeat MTB visitors
After familiarizing themselves with the results of the broad search provided by the ‘Quick Organ/Tissue Search’ option, a user may decide they would like to refine their search parameters. The ‘Tumor’ search form allows users to ask more complex questions, such as “Which strains of mice spontaneously develop adrenal gland pheochromocytomas that metastasize?”. This search may be performed by choosing ‘adrenal gland’ from the ‘Organ/Tissue of Origin’ menu as before and then adding ‘pheochromocytoma’ from the ‘Tumor Classification’ menu and ‘None (spontaneous)’ from the ‘Treatment Type’ menu. Finally, the question can be restricted further by checking the box beside ‘Restrict search to metastatic tumors only’. This search will return five records for spontaneous, metastatic pheochromocytomas, all of which arose in targeted mutant mice. As with the other ‘Tumor Results’ pages, the user can view more detailed information for each tumour record by clicking on the ‘Summary’ hyperlink for the record of interest.
Geneticists and developers of mouse models of human cancers
Many researchers will be primarily interested in a particular strain (either inbred or mutant) rather than in a particular type of tumour. In this case the ‘Strain’ search form is a good starting point. For example, searching for records in which the ‘Strain Name’ contains ‘Kras
’ and the ‘Strain Type’ is ‘targeted mutation (knockout)’ returns seven records for strains carrying a knockout allele of Kras
, either singly or in combination with some other mutation, on a variety of genetic backgrounds. Clicking on one of the hyperlinked strain names brings the user to the ‘Strain Tumor Overview’ page on which are listed all the tumour types analysed in those particular mice. The default view for this page is the ‘Collapsed View’, which shows data on the tumour type, organ(s) affected treatment type, and includes a link to additional information on the tumours. There are also links to other resources citing these mice (when applicable). These resources include places where mice may be obtained, such as the JAX® Mice web site and the Mouse Models of Human Cancers Consortium's (MMHCC's) Mouse Repository as well as data resources such as the Mouse Phenome Database (MPD), the Biology of the Mammary Gland Web Site, and Festing's Listing of Inbred Strains of Mice (see URLs in Further information
). Clicking on the ‘Strain Tumor Overview Expanded View’ link at the top of the page will expand the provided table to include metastasis data and specific related reference identifiers with hyperlinks to additional reference information. On either of the views, clicking on the hyperlinked numbers in the right-hand column will present the user with a ‘Tumor Summary’ page for that tumour type in those particular mice.
Researchers interested in investigating the role of a specific gene or genes in tumorigenesis can search MTB for specific genes using the ‘Genetics’ search. For example, a researcher studying Cdkn2a may want to explore all of the strains and tumours in MTB that have been reported to harbour a mutation in this gene. By choosing the ‘Genetics’ search form, entering Cdkn2a in the ‘Gene/Marker’ field, and clicking on the ‘Search’ button, the subsequent results page provides the user with data regarding mutant strains in which the mutation involves Cdkn2a (in this case there are both targeted mutant and transgenic strains) as well as data regarding tumours that have been reported to harbour a mutation in the Cdkn2a gene. These somatic mutations are changes such as point mutations, deletions and loss of heterozygosity. The strain section of the results page provides the user with information regarding the mutation type, mouse chromosome, gene symbol and name, and genotype of the mice. The hyperlinked numbers beside each genotype will provide users with a list of all the strains in MTB carrying the associated genotype. The tumour section of the results page provides the user with information regarding mouse chromosome, gene symbol and name, and the type of genetic change observed in the tumour. Hyperlinked numbers beside the type of genetic change will link the user to a page with additional information on the specific mutations as well as on the number and classification of the tumours found to carry those mutations. From there users may click on a link to view details of one or more of those tumour records.
Pathologists and pathology students
One of the sections of the database many users find most valuable is the pathology image archive. Researchers characterizing neoplasms from a newly developed mutant strain may wish to compare the tumours they have observed with other examples of the same tumour type from other strains of mice. This type of data can be accessed using the ‘Pathology Image’ search form. For example, one might want to compare the histopathology of mammary fibroadenomas in mice. A query for ‘mammary gland’ in the ‘Organ/Tissue of Origin’ menu and ‘fibroadenoma’ in the ‘Tumor Classification’ menu returns two pathology reports. Each report lists the tumour name, organ(s) affected, treatment type and agents (if applicable), strain name, sex, reproductive status, tumour frequency, age at necropsy and a short description. Under the report summary are thumbnail images, each with its own caption, written by a pathologist. Clicking on any of the thumbnail images will present the user with an enlarged version of the image along with all the associated data relevant to that image (). Many of the images currently held in MTB are displayed using the dynamic Zoomify viewer (see Zoomify and Zoomify movie URLs in Further information
). This viewer allows users to zoom in and out and pan around high-resolution image files so that the image can be viewed in greater detail than would be available from a handful of static JPEG images.
Images of tumours can also be added to MTB. These can be images from a published paper (if allowed by copyright) or they can be additional images collected during a study but not published. MTB has designed an online image submission system to facilitate community pathology image contribution through the inclusion of the ‘Submit Pathology Images’ link. Each mouse record in the submission system may be associated with one or more diagnoses, and each diagnosis may be associated with one or more images (). Submission of photomicrographs of cancer case material to MTB by the scientific community are much encouraged.
Experienced MTB users
Although the search forms already discussed provide the user with multiple avenues to delve into the data in the database, many users may find it most useful to perform a combination search, one that allows the user to specify both strain-specific and tumour-specific search terms. This type of search may be done using the ‘Advanced’ search form. For example, it may be useful to a researcher to search for transgenic mice that were developed on an FVB strain background and identify those mice that develop metastatic mammary adenocarcinomas (). Such a search returns the first 25 records of a total of 92 that are found. It is worth noting that the user may return to the search form and choose the ‘No Limit’ option to retrieve all 92 records. The results returned from this search are formatted in the same way as results from a ‘Tumor’ or ‘Quick Organ/Tissue’ search, and links to images (where available) as well as to the additional data given on the subsequent ‘Tumor Summary’ pages are also displayed.
All MTB users
As many of the data in MTB are derived from the published literature, searching by reference can be a useful tool. This may be done using the ‘Reference’ search form. For example, searching for the word ‘myoepithelioma’ in the title field returns one result with a hyperlinked ID number that will access a ‘Reference Detail’ page. This page provides the user not only with details regarding the specified reference but also with a summary of the numbers of tumours, pathology images and strains that have been annotated to that reference in MTB as well as links to those data. This page also provides a link to the MGI reference page, from which users may access PubMed and, where available, download the original reference.