This document is intended to help users interpret and navigate many of the functions available in MGI. If you have not worked with model organisms before, you may also find the Introduction to Mouse Genetics a helpful resource for terminology and the basics of using mice in an experimental genetic context.
MGI is a comprehensive, authoritative and curated international database resource, designed to provide free access to integrated genetic, genomic and biological data gathered from the greater research community. Data is derived from curation of the primarily literature, direct submission by researchers or research projects, and through data loads from other public resources. Each piece of information in MGI is associated with its source, indicated by a J:#.
Within MGI, information is not merely presented as described in a publication, but organized, integrated, and translated into metadata using standardized structured vocabularies. These well-defined terms can be used to annotate (or retrieve) information at whatever level of precision has been investigated or is desired, associate similar observations to one another, and provide information on relationships between terms. Importantly, they are also stable, unique and can be parsed by a computer for bioinformatic analyses. Three major structured vocabularies, also known as "ontologies", are developed and used by MGI: the Mammalian Phenotype ontology which describes abnormal observations in mutant animals, the Gene Ontology (GO) which describes the normal behavior of a gene or gene product within it's cellular context, and the Mouse Developmental Anatomy ontology which describes mouse anatomical structures throughout development, used for annotation of gene expression and cre recombinase activity results.
To access all of the data in MGI about a specific gene, you can simply enter the gene symbol, name, or synonym into the Quick Search window near the top of every MGI page.
|Results are ranked by how well they match the search input. In this example
There is a wealth of information and links to be found on Gene Detail pages. The gene detail page for Irf8 is shown on the left. Each row contains information and links to a particular data type associated with this gene. Some rows are open by default, while others are closed with additional information available. Click "more" () and "less" () arrows within the row to change the display.
The Homology ribbon is closed by default. Click the more/less button to expand and see more detail.
MGI loads homology assertions from both NCBI HomoloGene and the HCOP/HUGO Gene Nomenclature Committee. Species represented include mouse (Mus musculus), human (Homo sapiens), rat (Rattus norvegicus), chimpanzee (Pan troglodytes), Rhesus macaque (Macaca mulatta), dog (Canis familiaris), cattle (Bos taurus), chicken (Gallus gallus), zebrafish (Danio rerio) and western clawed frog (Xenopus tropicalis).
To the right, see homology information for Carnitine palmitoyltransferase 1a, liver (Cpt1a).
The human ortholog, CPT1A, is displayed at the top of this section, together with any human gene synonyms, external IDs and positional information. Homology assertions displayed in MGI are always sourced, either to HomoloGene, HGNC or both (as in this case). HomoloGene is an automated system for constructing homology classes across complete genomes of many species, while HGNC is focused on human as the primary species of interest and combines several automated pipelines together with curator decisions. See their respective pages (linked above) for more information.
Below, see vertebrate homologs and retrieve sequences across all represented species by clicking on the hyperlinked homology class ID. Homologs may be ‘1:1’, ‘1:many’ or ‘many:many’. In this example, mouse Cpt1a has a 1:1 homology relationship with human CPT1A, but a 1:2 relationship with zebrafish cpt1aa and cpt1ab (paralogous duplication).
The last column on this table allows you to download FASTA sequences for homologous protein (NP or UniProt links) and mRNA transcript sequences (NM links). To view a Multiple Sequence Alignment (protein level), click the link indicated above the table which links out to NCBI tools.
The Disease ribbon is closed by default. Click the more/less button to expand and see more detail.
MGI provides curated gene-to-disease relationships for both human and mouse in cases where that relationship is well supported. For human, we load these relationships from data curated by Online Mendelian Inheritance in Man (OMIM) staff. For mouse, MGI curators rely on explicit, traceable author statements that a particular mouse mutant is a model for a given human disease.
To the right, see the disease table for Kras.
If mutations in a gene have been described as causing disease in humans, a small human icon will appear next to that row (ex. ‘KRAS-lung cancer’ and ‘KRAS-bladder cancer’). If a mouse mutant has been described as a model of a human disease, a mouse icon will appear (ex. ‘Kras-lung cancer’ and ‘Kras-prostate cancer’). In many cases these will agree, and both icons appear together. When gene-to-disease relationships appear in one species only, this often simply indicates missing data as a mouse mutant may not been examined and described within this disease context, and/or a human clinical case of the disease with mutations in this gene may not have been found and curated (yet). If a mouse model was specifically examined for a disease and found by researchers to not sufficiently reproduce the necessary equivalent phenotypes, the association will be reported with a "NOT" qualifier (ex. ‘Kras-Leukemia, Acute Myeloid; AML’ - see option to "view 1 NOT model" for details).
Click on the hyperlinked disease name (#1; Pancreatic cancer ) to go to a Human Disease and Mouse Model Detail page. Tables on these pages include all genes that have been implicated as causing that disease in human cases or mouse models.
Click on the hyperlinked ‘view # models’ (#2) to view exactly which mouse genotypes have been described as exhibiting the characteristics of a model for human disease (view 1 model for Noonan Syndrome 3). This pop-up will record the specific allele pair (i.e. Krastm4.1Bbd; click to view the biological properties associated with this mutation on the allele detail page), the mouse strain background, annotated phenotypes and the reference describing this mouse as modeling the human disease indicated (J:#).
Mutations, alleles and phenotypes
The Mutations, Alleles and Phenotypes ribbon on a gene detail page provides an at-a-glance text and grid summary of the major phenotypes associated with mutations in this gene, as well as links to all described alleles.
The example on the right shows the Mutations, alleles and phenotypes ribbon for the Plod1 gene.
Below the grid, a short sentence summary (Phenotype summary sentence) is written by MGI curators to highlight some of the more salient phenotypic observations.
The grid (Structured MP top-level slim grid) lists all of major phenotypic systems comprising the Mammalian Phenotype (MP) ontology. Blue squares indicate that a phenotype within a given system can been directly attributed to mutations/alleles of this gene, white squares indicate that no annotations within this system have been recorded. Blue squares are clickable (see arrow) which will generate a pop-up (Mammalian Phenotype annotations related to [system]) describing which alleles were used to make the annotation, and the specific phenotype terms that were curated. These pop-ups are also clickable, and clicking on either allele IDs (format: GenesymbolUniqueID) or slim grid sub-terms will generate a genoview page (not shown) that includes curator comments as well as the structured terms, and provides a reference for each observation. This page can also be reached using the links in the Phenotype Summary above the grid.
To locate a complete list of alleles that have been reported for this gene, look to the top right corner of the ribbon where an All Mutations and Alleles link appears, subdivided below by various relevant allele generation types. See Introduction to Mouse Genetics: Alleles for more information on the biology differentiating these.
Clicking on these links (arrow) will open a new page for the Phenotypic Allele Summary. This table lists each allele with a unique ID in the first column, synonyms, affected phenotypic systems for this mutant and the allele generation method and attributes in the Category column. Clicking on an Allele Symbol will bring you to an Allele detail page.
Gene Ontology (GO) Classifications
Gene Ontology (GO) uses a set of standardized, controlled structured vocabulary terms to describe the function, biological process involvement and cell component of gene products. GO for mice is developed in collaboration with the Gene Ontology project (see also GO at MGI). Unlike the Mutations, Alleles and Phenotypes section just above, GO describes the normal behavior of the gene or gene product within it's cellular context, not abnormalities observed in mutants.
On the right is an example of the Gene Ontology (GO) Classification ribbon in Bbs1.
This ribbon contains three grids chosen by GO to provide a broad representation of all underlying data. Left grid is Molecular Functions (elemental activities, such as catalysis or binding), center is Biological Process (a collection of molecular events forming a process pertinent to the functioning of living things, such as signaling or metabolism), and the right grid for Cellular component (the part of a cell or external environment where the gene product is located).
Blue squares are clickable which will generate a new page with underlying data for the intersection of gene and GO category, together with evidence and references (see arrow).
To retrieve the list of all vocabulary terms that have been annotated to this gene, click on the hyperlinked number next to "All GO Annotations".
Expression of a gene can vary from ubiquitous to restricted by a particular tissue type and/or developmental stage. In the gene Expression ribbon, you can explore an overview of gene expression curated by the Gene Expression Database, with a focus on endogenous expression during development. The slim grid provides an overview of the major tissues and organ systems present in a mouse across development based on the Mouse Developmental Anatomy ontology.
To the right is the Expression ribbon for Foxn1.
Blue squares indicate that the gene is expressed in this system, grey triangles indicate that all data system is derived from some other type of annotation, including gene expression examined and absent, or expression data from mutant lines. White indicates that no expression annotations are present within this system.
Filled cells (blue or grey) are clickable to reveal more detailed structures and annotations (see arrow). On the Gene Expression Data page that appears, a Tissue x Stage matrix appears with expression annotations arranged by tissue in rows (use triangle toggles to retrieve more specific annotations) and developmental stages displayed in columns. In this table, the TS prefix refers to Theiler stages of embryonic development: TS1-TS26 are embryonic, TS27 is perinatal and TS28 is adult.
A legend on this page outlines fill color and shading. Briefly, blue is used to demonstrate that gene expression has been detected at a given tissue and stage, red demonstrates that gene expression was examined and found to be absent, and gold indicates tissue and stage combinations where the underlying annotations are negative or ambiguous, but within substructures. Darker shading is used to indicate the presence of more data but is not necessarily related to higher expression of the gene. If the intersection appears blank (white), there is no expression data within GXD for that combination.
Apply filters to refine your results, and click on shaded cells or navigate other tabs to see more specific supporting data with references, images, or download data.
This page includes additional tabs, for more detail on interpreting each, see How do I interpret the results of my expression search?
On protein coding gene detail pages, the microRNAs targeting the feature will appear (see right for the protein coding gene Lpp), or, on microRNA gene detail pages (see Mir181a-2 for an example), the gene targets will be displayed. Click the View All button (#1) to see all interactions in tabular and graphic format in the Interaction Explorer.
The table lists the interacting features, the nature of the interaction, data source and either a validated status or a prediction score, normalized along a 0 to 1 scale. For more about prediction scores, see the About MGI Interaction Data at the top right of the page. Columns may be sorted using arrows in the header row, or apply filters using the options at the top of the page (#2).
To download the entire dataset, use the Download data link (#3). For table data, reflecting any filters that have been applied, use the Batch Query button, which further allows you to add Gene Attributes and Additional Information if desired, by expanding the Click to modify search button that appears above the table on the linked page.
The hairball graphic (#4) can be used to visualize the data in the adjacent table. Validated interactions are linked with blue lines and predicted interactions with red lines. If a feature–feature interaction has been reported from multiple data sources, it will appear in the inner ring. Applying filters alters the graphic display as well as the table.
In brief, allele symbols are typically formed for endogenous genes (including mutant and targeted alleles) according to GeneSymbolAlleleID where the AlleleID is:
To follow the example below, open the allele detail page for Trp53tm1Brd.
A color coded key representing allele state appears above the genotypes table (#1) which reports allele composition, genetic background and cell line. Genotypes are differentiated by allelic composition (allele symbol, zygosity, additional alleles, recombinases or transgenes if present) and genetic background, typically inbred or a combination of inbred lines. If either the allelic composition or genetic background varies, a new genotype ID (hm1, hm2, ...) and row will appear. For guidelines and interpretation of strain nomenclature, see here.
Each row in the genotypes table corresponds to a column in the Phenotypes table below.
Each column in the phenotypes table reflect the phenotypes and observations associated with the matching row in the genotypes table (#1).
Expand affected physiological system terms by clicking the triangles within the row ( #2) to reveal more detailed structured vocabulary terms. If at least one differential phenotype has been reported for males and females, columns will be subdivided with icons just below the genotype header. Clear spaces indicate that no phenotype was reported, and an "N" will appear if the system was specifically examined and reported as "Normal".
Clicking on check marks or column headers will generate a pop-up window for that genotype (#3) with free text descriptions (#4) and associated references for those annotations (#5).
Links appear in the Find Mice (IMSR) row if a mouse strain or pluripotent ES cells carrying the mutation are available for purchase through any of the major international repositories indexed by the International Mouse Strain Resource (IMSR). If links do not appear, this means that the strain has not been deposited for commercial distribution, however it may still be possible to obtain mice by contacting the researcher who developed the line initially. His or her information can be located in the Nomenclature or Mutation Origin section (see J:# next to "Earliest citation of germline transmission") at the top of the allele detail page, or in the reference specified as "Original" at the bottom.
If a mouse or ES cell line is available carrying the exact allele from this allele detail page, a hyperlinked number will appear next to "Carrying this Mutation:" (#1). If other alleles of the same gene exist and are commercially available, another hyperlinked number will appear below, next to "Carrying any GeneSymbol Mutation:" (#2).
Available strains will be indicated including the full genotype (see
Strain Name for inbred background), state (live/embryo/sperm/ES cell line),
repository (provider, #3) and allele
details (#4). Confirm in the "Genes" and
"Alleles" columns (#4) that the strain
carries only (or all of) the mutations that are desired.
Once satisfied, you can find purchasing information (prices, timelines, MTAs) and place an order by clicking on the Order button (#3). For purchasing or strain specific questions, you can also contact the repository directly by using the purple envelope icon.
Query forms allow researchers to set parameters and retrieve gene (or other) lists that match a term or terms of interest. Query forms are organized by topic, and can be accessed either from the Search dropdown menu in the dark blue bar at the top of the page, or by selecting a topic from the list below the Quick Search on MGI's home page (#1). Clicking on Search will open a list with All Search Tools (#2) where you can see names and brief descriptions of the search tools available. Click on the hyperlinked query forms to open. Clicking on topic buttons will open a minihome landing page corresponding to that topic (#3). Minihome landing pages list relevant query forms (#4) as well as FAQ guides for common queries (#5).
Each query form allows you to specify what you are searching for, place constraints or parameters in order to tailor your search more effectively and choose options for results output. Each field in the query form is optional; leave fields blank to default to "all". Use the FAQ to walk through several examples of searches using query forms and to help choose the best form to answer your biological question. The FAQ index can also be accessed by following the link beneath the MGI logo in the header of all MGI web pages.On each query form, clicking the question mark icon in the top left of the page will generate a pop-up window with form-specific user documentation.
Example query: how to find a list of genes annotated to a particular phenotype or function
To retrieve a list of alleles satisfying your query, use the Phenotypes, Alleles & Disease Models Search, found on the dropdown menu via Search > Phenotypes > Phenotypes, Alleles and Diseases Query or from the Phenotypes & Mutant Alleles home page.
This example will use the Genes and Markers query to search for all protein–coding genes where a mutant allele has been involved in a genotype annotated to embryonic lethality.
Example query: how to retrieve MGI IDs (or other IDs) for a list of genes
Use the Batch Query, found on the dropdown menu via Search > Batch Query or from the Batch Data and Analysis Tools link from the homepage to add IDs, attributes or other information to a list of genes or probes.
This example will use the Batch Query to add MGI and Ensembl IDs to the genes Cacna1a, Ifng, Cxcl9, Pax2 and Trp53.
Example query: how to find gene expression data in a specific tissue, at given developmental stage
Use the Gene Expression Data Query, found on the on the dropdown menu via Search > Expression > Gene Expression Data Query or from the Gene Expression Database (GXD) homepage, to access integrated gene expression data and images provided by GXD.
This example will use the Expression Data Query to retrieve a list of genes assays and images with annotations to the embryonic heart at E15.5.
See more about Expression in the Gene Detail:Expression section here.
Starting from a Reference
Many users come to MGI looking for more information about a particular mouse allele or strain that they encountered while reading through scientific literature. If multiple alleles of a gene exist, it may not be immediately clear which allele corresponds to the one from that publication, especially if the authors did not use standard allele nomenclature for the allele symbol.
Enter some element or elements and click Search to continue.
|The search will match according to your input; in this case an Any
Author search for Gros, P. See above the results table (#1)
to see what was entered. You can modify your search from this page or add filters
to narrow your list of results if desired.
The results table (#2) will return the complete citation for all references matching your search that have been curated by MGI. If a paper has curated data (phenotypic alleles, sequences, expression records, functional annotations, mapping data, etc), these will be indicated in the central Curated Data column. For mouse mutants, click on phenotypic alleles (#3). A summary will appear with the details of the data (#4). In the example to the right, two different alleles of Jak3 were studied. Click on the Allele Symbol to go to the Allele Detail Page.
For more customization, or to work with large–scale data, MGI provides bulk reports available for download in tab delimited format, or several computational access options allowing users to generate their own reports and analyses. MGI reports are refreshed weekly and posted to an ftp site, see below.
Accessing batch data files
Over 75 batch files can located via the Download menu (#1), or from the Batch Data and Analysis Tools link on the homepage (#2).
Data are tab delimited (or pipe-delimited where indicated) with header rows. Each field represented in the data is described briefly in the header row on the index page. An example appears below.
Where coordinates are displayed, the genome build will also be indicated on the index page. For current coordinates, MGI uses GRCm38 with feature annotation from VEGA.
Files are in .rpt format, which can be opened by Mac or PC as plain text, readable by most browsers, text editors, Excel or other applications. If you do have difficulty opening these files, please contact User Support.
MouseMine computational access
MouseMine is a new computational access platform for MGI data that offers maximal flexibility, with numerous predefined templates, customizable queries, list enrichment tools and other list or analysis options. Results from MouseMine can be saved online, downloaded or forwarded to Galaxy.
MouseMine can be accessed from the Search drop down menu via Search > MouseMine, from the Batch Data and Analysis Tools link on the homepage, or by direct url at http://www.mousemine.org/mousemine/begin.do
MouseMine has it's own documentation, see the Help and FAQ in the top right of the page (#4), or use the links in the First time here? box.
To upload a list, view a saved list, perform list enrichment analysis, or run queries from a list, use the Lists tab (#2).
For computationally savvy users, build custom queries through the Query Builder tab (#3). Please use the link to browse the data model to ensure that your query will search against the expected data structures. Additional documentation can also be found through InterMine.
Create an account to save lists and queries (#4), or contact MouseMine developers with questions.
See just above on this page to access MouseMine.
Download slides (if desired) by clicking the SlideShare footer from the frame on the right.