Database content
The most recent version of the database comprises data on the mouse models of 9 polyQ diseases. It contains basic information about the mouse models, such as their genetic design, and detailed descriptions of the disease phenotypes. Moreover, the database contains information regarding therapeutic approaches evaluated in polyQ mice, including information about drugs and the phenotypes that were evaluated as therapeutic outcomes. Figure 1 presents the current structure of the database (see Materials and methods). Table 1 presents the overall number of records for selected tables and short description of the records.
Online interface and query of the database
The online interface to the database is organized as a web page with a “Search” tab and three thematic tabs entitled “Models”, “Phenotypes” and “Therapies” (Fig. 2a). The three thematic tabs in the online interface are designed to present and group the search results with respect to models, phenotypes and therapies.
Using the “Search” tab, the user may perform a classic text search, and the results are displayed in the remaining three thematic tabs “Models”, “Phenotypes” and “Therapies”. Instead of performing the text search, the user may also opt to perform an “intuitive” search using lists and pictograms available in the “Models”, “Phenotypes” and “Therapies” tabs (Fig. 2b,c). The intuitive search is performed by selecting the disease and most common mouse models from the list in tab “Models”, selecting the phenotype location on the brain diagram (Lein et al. [24]) and pictograms of other central nervous system (CNS) and non-CNS organs and tissues in tab “Phenotypes” (Fig. 2b) and selecting from more than 20 therapeutic strategies using 6 icons, which schematically group the strategies (Fig. 2c).
Keywords to perform a classical text search of the database
To search the database, several types of inputs can be used, including the diseases (e.g., “HD”, “SCA3”), common name of model (e.g., “R6/2”, “Ki91”), detailed phenotype (e.g., “inclusions”, “incoordination”), location (e.g., “cortex”, “cerebellum” or “liver”), detailed location (e.g., “Purkinje”), drug (e.g., “minocycline”) and therapeutic strategy (e.g., “apoptosis”, “cell therapy”). Keywords can be constructed using Boolean operands “AND”, “OR” and “NOT” which can be used several times in one query or used in complex queries containing both “AND”, “OR” and NOT. Original publications can be accessed by searching their PMID or the first author of the publication.
Search process ultimately yields the search results in thematic tabs that offer methods to refine the search results through selections from drop-down lists. Selecting a record in any of the thematic tabs results in the display of a detailed mouse model page, which contains a model name as a header and is focused on a particular model and either phenotypes or therapies. If both therapies and phenotypes are available for the given model, the detailed mouse model page allows switching between the phenotypic and therapeutic views.
Examining the search results in the “Models”, “Phenotypes” and “Therapies” tabs
The “Models” tab in the online interface mostly collects data from “Model” and “Model Phenotype” tables present in the structure of the database. After performing the text or intuitive search, the “Models” tab will appear first and present the range of mouse models (Fig. 3a). From within the “Models” tab, the user is able to select a model, which will present a detailed mouse model page (Fig. 3b) with basic information about the particular mouse model, such as mouse model name, modeled disease, model type, promoter, transgene and the reference of the original description of the model. The page with model details also contains information about genetic background, number of polyQ, an external link to the JAX Mice Database webpage and, most importantly, the phenotypes or therapeutic approaches in the model. For instance, in the R6/2 detailed mouse model page, the user can find that this is a transgenic HD model that contains the human HD promoter and expresses the N-terminal fragment of human huntingtin (HTT) protein with a 120 polyQ stretch.
The “Phenotypes” tab collects data from the “Model Phenotype” table found in the structure of the database. The records displayed in the “Phenotypes” tab provide an overview of the manifestation of the disease in a mouse model. The phenotypes in the database are subcategorized into four main types: “cognitive”, “motor”, “neuropathology” and “other”. Phenotypes in these groups are further subdivided into “phenotype” and “detailed phenotype”, which provide additional levels of phenotype complexity and enabling a methodical incorporation into the database. The above structure of the phenotype description is reflected in the “Phenotypes” tab. The records presented in the “Phenotypes” tab show phenotype manifestation in a particular model, its details, disease, model name and the reference. The search can further be refined using parameters, such as location of the phenotype in tissues selectable from dropdown lists. Selecting a model in “Phenotypes” tab opens a detailed mouse model page in the “phenotype mode” (Fig. 3b). The detailed mouse model page in this mode provides a list of phenotypes, which can be expanded or collapsed again to visualize or hide the detailed description box for each phenotype. The detailed box for each phenotype (Fig. 3c) contains a graphical representation of the age of mice when the phenotype is manifested, the information about the decreased or increased phenotype in mutant mice compared with wild type (WT) mice, number of repeats in the transgene (Q number), genetic background of mice and the Pubmed link.
The tab “Therapies” summarizes the therapeutic approaches using data from “Therapy” table found in the structure of the database. The therapeutic approaches listed in the “Therapies” tab contain the therapeutic strategy, drug that was applied to the mouse model, disease, model name and the reference. Similar to other thematic tabs, selecting a therapeutic approach will open a detailed mouse model page in the “therapeutic mode”. The detailed mouse model page in this mode provides a list of therapeutic records, each containing a drug, the respective mouse phenotype and detailed phenotype that was affected by the drug and the color-coded therapeutic outcome. Each therapeutic record from the list can be expanded or collapsed to visualize or hide the detailed box. The detailed box for each therapeutic record contains details, such as drug feature or aim, delivery route, therapeutic strategy, method of quantification of the therapeutic effect, effect on this phenotype, and description of the effect by listing whether “mutant vs. WT” and “treat vs. mock” was “decreased” or “increased” (Fig. 3d).
Interaction with users
The database also contains a dedicated “submit data” page where research publication from Pubmed containing mouse models can be submitted to the database for further verification by database administrators. The dataset of the database is also available for research users upon request by e-mail to mfigiel@ibch.poznan.pl. In addition, the database is open for models of other neurological diseases, such as Alzheimer and Parkinson, and also for other model species.