Mouse Genome Informatics (MGI): latest news from MGD and GXD

Abstract

The Mouse Genome Informatics (MGI) database system combines multiple expertly curated community data resources into a shared knowledge management ecosystem united by common metadata annotation standards. MGI's mission is to facilitate the use of the mouse as an experimental model for understanding the genetic and genomic basis of human health and disease. MGI is the authoritative source for mouse gene, allele, and strain nomenclature and is the primary source of mouse phenotype annotations, functional annotations, developmental gene expression information, and annotations of mouse models with human diseases. MGI maintains mouse anatomy and phenotype ontologies and contributes to the development of the Gene Ontology and Disease Ontology and uses these ontologies as standard terminologies for annotation. The Mouse Genome Database (MGD) and the Gene Expression Database (GXD) are MGI's two major knowledgebases. Here, we highlight some of the recent changes and enhancements to MGD and GXD that have been implemented in response to changing needs of the biomedical research community and to improve the efficiency of expert curation. MGI can be accessed freely at http://www.informatics.jax.org .

Fig. 1

A Tabular summary of the Eva1c gene (MGI:1918217) annotation across multiple strains of mice with three strains selected. B Screenshot of the Multiple Genome Viewer showing the Eva1c and surrounding annotations for the strains selected in the strain annotation distribution table

Fig. 2

Screenshot from MGD’s Human–Mouse Disease Connection (HMDC) A Results of search for the gene Fgfr3 (MGI:95524) showing the ribbon format overview of phenotype term annotation similarities of mouse and human. Cells with orange indicate annotations for the human gene for a phenotype term. Cells with blue shading indicate annotations for a mouse gene for a phenotype term. Cells with both orange and blue indicate a phenotype term shared by mouse and human. Depth of color indicates the number of published annotations. Mouse genes starting with “Tg” represent transgenic mice carrying either the mouse or human Fgfr3 gene. B Arrow indicates the results of clicking on a cell for a disease term showing specific disease annotations at the gene level for human and at the genotype level for the mouse. The “Find Mice” button is a link to the International Mouse Strain Resource (IMSR) (Eppig et al. 2015b) which lists the availability of mouse models from repositories around the world

Fig. 3

Anatomical comparison of expression and phenotype data. A Comparing expression and phenotype data for a specific anatomical structure. The Mouse Developmental Anatomy Browser allows users to search for anatomical structures and to look up the expression and phenotype data associated with these structures. ‘Endocrine pancreas’ is shown as example. Using the Tree View (lower right), one can explore the anatomy by expanding and collapsing the hierarchy. The links indicated by arrows in the Tree View section lead to the expression and phenotype data associated with the selected anatomical structure and its substructures. The link (arrow) in the Term Detail section (upper right) leads to the Mammalian Phenotype (MP) browser, listing the MP terms mapped to the selected anatomical structure, and phenotype data associated with these MP terms. B Comparing expression and phenotype pattern for a specific gene. The Gene Expression + Phenotype Matrix displays the expression and phenotype data for a selected gene in the same anatomical matrix view. The gene Ins2 is shown as an example, with the ‘endocrine system’ expanded along the anatomy axis. The wild-type expression pattern of Ins2 is displayed in the first column (gold header), the following columns show the anatomical structures phenotypically affected in different Ins2 mutant mice (different Ins2 alleles). The coloring of the matrix cells gets progressively darker as the number of expression and phenotype annotations increases; the conventions are defined in the matrix legend (inset)

Fig. 4

Hypothalamus expression results in GXD for genes involved in homeostasis. A Partial search result set shown from a search for expression data assayed in mouse hypothalamus and then filtered for genes annotated to GO Biological Process term: homeostatic process. Classical GXD expression data are integrated with RNA-Seq data via curated source metadata. Assay-level filters allow results to be narrowed by selected sample metadata fields (Anatomical System, Theiler Stage, Assay Type and whether mutant or wild-type mice were assayed). Gene-level filters allow results to be refined by qualitative (Detected?) and quantitative (TPM Level) expression. Gene-level filters also refine results to sets of genes annotated to biological systems of interest (Gene Ontology, Mammalian Phenotype Ontology, Disease Ontology). Expression results are organized into separate views/tabs. The default Assay Results view (shown truncated at the dotted line) displays sample-level metadata for each assayed gene (assay reference column not shown). For classical expression assay types, links in the images column lead to complete assay details including thumbnails of corresponding images, from which details for each image can be accessed (insert shows image detail from (Koscielny et al. 2014)). For RNA-Seq data, a row represents the consolidation of biological replicates, and TPM Level bins are shown for each gene, based on the average, quantile-normalized TPM values from corresponding biological replicate samples with the number of biological replicate samples provided. Clicking the RNA-Seq Heat Map button (red heat map arrow) renders a Morpheus RNA-Seq heat map of the query results. Additional views/tabs for the expression result set (not shown) feature search results organized by Genes, Assays, Images, or two matrix views of the data (Tissue x Stage matrix and Tissue x Gene matrix). Selected filters affect results on all display tabs. B RNA-Seq heat map of GXD results from the filtered query rendered with Morpheus (partial heat map shown). Columns represent distinct sample bioreplicate sets and are labeled by a combination of anatomical structure, experiment ID, and bioreplicate set ID (stars represent mutant samples). Metadata shared between samples are indicated by distinct colors in the metadata rows above the gene rows. Colored cells in gene rows reflect average, quantile-normalized TPM values for corresponding columns using a TPM value color scheme that accounts for an expansive dynamic TPM range (dark blue (high) to light blue (low), gray = below threshold, not present in the section of the heat map shown). Genes and samples were clustered using the Hierarchical Clustering feature of Morpheus (Euclidean distance, complete linking). Although the heat map is cropped to show only a few of the 1,893 genes in the result set, both gene-level and sample-level clustering are evident. Notably, the mutant samples (stars) cluster from the wild-type samples and are derived from mice with a mutation in the Sox2 gene (Sox2^tm1.1Lan, ArrayExpress: E-MTAB-7496, (Cheng et al. 2019)