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. 2014 Jan;42(Database issue):D825-34.
doi: 10.1093/nar/gkt1159. Epub 2013 Nov 15.

Mouse phenome database

Stephen C Grubb  1 , Carol J Bult, Molly A Bogue
Affiliations

Mouse phenome database

Stephen C Grubb et al. Nucleic Acids Res. 2014 Jan.

Abstract

The Mouse Phenome Database (MPD; phenome.jax.org) was launched in 2001 as the data coordination center for the international Mouse Phenome Project. MPD integrates quantitative phenotype, gene expression and genotype data into a common annotated framework to facilitate query and analysis. MPD contains >3500 phenotype measurements or traits relevant to human health, including cancer, aging, cardiovascular disorders, obesity, infectious disease susceptibility, blood disorders, neurosensory disorders, drug addiction and toxicity. Since our 2012 NAR report, we have added >70 new data sets, including data from Collaborative Cross lines and Diversity Outbred mice. During this time we have completely revamped our homepage, improved search and navigational aspects of the MPD application, developed several web-enabled data analysis and visualization tools, annotated phenotype data to public ontologies, developed an ontology browser and released new single nucleotide polymorphism query functionality with much higher density coverage than before. Here, we summarize recent data acquisitions and describe our latest improvements.

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Figures

Figure 1.
Figure 1.
Improved intervention and methodology classification and browsing. The interventions page has been restructured, and trade name equivalents added for all drugs to our existing catalog of synonyms. Interventions are grouped in these sections: diet-related, drugs and alcohol, exercise, pathogens/parasites and toxicity/challenges/mutagens. Measurements have been annotated to a controlled vocabulary of methodology (apparatus, platform). This was done with the recognition that sufficiently classifying behavioral data is more complicated than other phenotypic domains (some users search on apparatus, like ‘open field’; others prefer to search on behavioral area, like ‘exploratory’). Note that only partial lists are shown for both interventions and methodologies.
Figure 2.
Figure 2.
New ontology navigator and connecting to other databases (example: nicotine). The ontology browser is accessible through the ‘phenotype’ button on the homepage (Figure 1). Users enter a search term; in this example, there are two MP terms annotated to MPD measurements (upper left panel). Clicking on the term displays the definition and parent terms in the hierarchy (middle left panel). To find data annotated to this term, click on the red number as indicated by the red arrowhead; the red number shows the number of measurements directly annotated to this term. Users then get a list of available measurements to choose from (upper right panel; only a partial list is shown). Clicking on a measurement link takes users to a plot (lower right panel). In this case, 129S6/SvEvTac shows an ‘enhanced behavioral response to nicotine’. As shown in the bottom left panel, MPD provides term linkouts to MGI (31), Rat Genome Database (32) and GeneWeaver (33). This example showcases data from the new MPD project: Gould2 (34,35).
Figure 3.
Figure 3.
New visualization and analysis tools for Collaborative Cross data. The new CC tool plots all strains tested in a single view (upper panel), which can be wide, as in this case, where 139 strains are shown (females were not tested in this study). Founder strains are highlighted in green; overall mean and standard deviation are indicated by the horizontal dotted lines. A distribution histogram is one click away (lower left panel); for quick reference, founder strains are plotted above the histogram (mean, standard error). A data table (lower right panel, partial list) is available just below the primary plot on the Web site, showing values for strains in alphabetical order (default); up- and down-triangles indicate high- and low-end outlier strains, respectively. From here, users can opt to view data by magnitude order and view more detailed summary statistics. This example uses data from the new MPD Project: Collins1 (16,17).
Figure 4.
Figure 4.
New visualization and analysis tools for Diversity Outbred populations. The new DO tool renders distribution histograms (left panel: female above, male below). Founder strains means and standard error are plotted above the histograms for quick reference. A data table is one click away (lower right panel), showing values for strains in alphabetical order (default); up- and down-triangles indicate high- and low-end outlier strains, respectively. From here, users can opt to view data by magnitude order and view more detailed summary statistics. This example uses data from new MPD Project: Chesler4 (11,27).
Figure 5.
Figure 5.
New MPD SNP query page and gene detail pages. Users must first enter genomic region (gene, marker, location or rs number; space-delimited lists can also be entered) and specify whether data sets will be manually selected and whether filtering will be implemented, e.g. polymorphisms between selected strains. The default settings use Sanger SNP data without any filtering. It is possible to ‘refine’ a query from results pages allowing users to make adjustments to the original specifications. In this example, we use results found by Logan et al. (11) and showcased in Figure 4 (MPD: Chesler4), where C57BL/6J, CAST/EiJ, NOD/ShiLtJ, PWK/PhJ and WSB/EiJ cluster in a group of strains that are not immobile in the open field test compared with the other CC founder strains, which cluster at the opposite end of the spectrum (129S1/SvImJ, A/J and NZO/HlLtJ). Logan et al. reported two QTLs for the immobility phenotype; one QTL is on chromosome 2 between 93.2–100.21 Mb. For this example, we plugged in the coordinates for this QTL and used filtering options to find polymorphic locations between the two clusters of strains (lower left panel: low immobility strains grouped to left, high immobility to right). We found four genes in this region that showed haplotypes segregating with the immobility phenotype (here showing two-color allele scheme; four-color nucleotide scheme is available as an option). Clicking on gene name takes users to the updated gene detail page. The new view shows nearby genes and markers (circled in red) with the option of viewing markers within ±50 kb (and subsequent increments). In addition, there is a link to SNPs, indels and structural variants in the region, a link to identify gene expression probesets in the vicinity and a link to find phenotypes that are correlated to those probesets. There are also convenient linkouts to other databases from gene detail pages. See text and Table 3.
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