Mouse Genome Informatics: an integrated knowledgebase system for the laboratory mouse.

Mouse Genome Informatics (MGI) is a federation of expertly curated information resources designed to support experimental and computational investigations into genetic and genomic aspects of human biology and disease using the laboratory mouse as a model system. The Mouse Genome Database (MGD) and the Gene Expression Database (GXD) are core MGI databases that share data and system architecture. MGI serves as the central community resource of integrated information about mouse genome features, variation, expression, gene function, phenotype, and human disease models acquired from peer-reviewed publications, author submissions, and major bioinformatics resources. To facilitate integration and standardization of data, biocuration scientists annotate using terms from controlled metadata vocabularies and biological ontologies (e.g. Mammalian Phenotype Ontology, Mouse Developmental Anatomy, Disease Ontology, Gene Ontology, etc.), and by applying international community standards for gene, allele, and mouse strain nomenclature. MGI serves basic scientists, translational researchers, and data scientists by providing access to FAIR-compliant data in both human-readable and compute-ready formats. The MGI resource is accessible at https://informatics.jax.org. Here, we present an overview of the core data types represented in MGI and highlight recent enhancements to the resource with a focus on new data and functionality for MGD and GXD.

The Mouse Models of Human Cancer database (MMHCdb).

The laboratory mouse has served for decades as an informative animal model system for investigating the genetic and genomic basis of cancer in humans. Although thousands of mouse models have been generated, compiling and aggregating relevant data and knowledge about these models is hampered by a general lack of compliance, in the published literature, with nomenclature and annotation standards for genes, alleles, mouse strains and cancer types. The Mouse Models of Human Cancer database (MMHCdb) is an expertly curated, comprehensive knowledgebase of diverse types of mouse models of human cancer, including inbred mouse strains, genetically engineered mouse models, patient-derived xenografts, and mouse genetic diversity panels such as the Collaborative Cross. The MMHCdb is a FAIR-compliant knowledgebase that enforces nomenclature and annotation standards, and supports the completeness and accuracy of searches for mouse models of human cancer and associated data. The resource facilitates the analysis of the impact of genetic background on the incidence and presentation of different tumor types, and aids in the assessment of different mouse strains as models of human cancer biology and treatment response.

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

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 .

Multiple genome viewer (MGV): a new tool for visualization and comparison of multiple annotated genomes.

The assembled and annotated genomes for 16 inbred mouse strains (Lilue et al., Nat Genet 50:1574-1583, 2018) and two wild-derived strains (CAROLI/EiJ and PAHARI/EiJ) (Thybert et al., Genome Res 28:448-459, 2018) are valuable resources for mouse genetics and comparative genomics. We developed the multiple genome viewer (MGV; http://www.informatics.jax.org/mgv ) to support visualization, exploration, and comparison of genome annotations within and across these genomes. MGV displays chromosomal regions of user-selected genomes as horizontal tracks. Equivalent features across the genome tracks are highlighted using vertical 'swim lane' connectors. Navigation across the genomes is synchronized as a researcher uses the scroll and zoom functions. Researchers can generate custom sets of genes and other genome features to be displayed in MGV by entering genome coordinates, function, phenotype, disease, and/or pathway terms. MGV was developed to be genome agnostic and can be used to display homologous features across genomes of different organisms.

Mouse Genome Database (MGD): Knowledgebase for mouse-human comparative biology.

The Mouse Genome Database (MGD; http://www.informatics.jax.org) is the community model organism knowledgebase for the laboratory mouse, a widely used animal model for comparative studies of the genetic and genomic basis for human health and disease. MGD is the authoritative source for biological reference data related to mouse genes, gene functions, phenotypes and mouse models of human disease. MGD is the primary source for official gene, allele, and mouse strain nomenclature based on the guidelines set by the International Committee on Standardized Nomenclature for Mice. MGD's biocuration scientists curate information from the biomedical literature and from large and small datasets contributed directly by investigators. In this report we describe significant enhancements to the content and interfaces at MGD, including (i) improvements in the Multi Genome Viewer for exploring the genomes of multiple mouse strains, (ii) inclusion of many more mouse strains and new mouse strain pages with extended query options and (iii) integration of extensive data about mouse strain variants. We also describe improvements to the efficiency of literature curation processes and the implementation of an information portal focused on mouse models and genes for the study of COVID-19.

The mouse Gene Expression Database (GXD): 2021 update.

The Gene Expression Database (GXD; www.informatics.jax.org/expression.shtml) is an extensive and well-curated community resource of mouse developmental gene expression information. For many years, GXD has collected and integrated data from RNA in situ hybridization, immunohistochemistry, RT-PCR, northern blot, and western blot experiments through curation of the scientific literature and by collaborations with large-scale expression projects. Since our last report in 2019, we have continued to acquire these classical types of expression data; developed a searchable index of RNA-Seq and microarray experiments that allows users to quickly and reliably find specific mouse expression studies in ArrayExpress (https://www.ebi.ac.uk/arrayexpress/) and GEO (https://www.ncbi.nlm.nih.gov/geo/); and expanded GXD to include RNA-Seq data. Uniformly processed RNA-Seq data are imported from the EBI Expression Atlas and then integrated with the other types of expression data in GXD, and with the genetic, functional, phenotypic and disease-related information in Mouse Genome Informatics (MGI). This integration has made the RNA-Seq data accessible via GXD's enhanced searching and filtering capabilities. Further, we have embedded the Morpheus heat map utility into the GXD user interface to provide additional tools for display and analysis of RNA-Seq data, including heat map visualization, sorting, filtering, hierarchical clustering, nearest neighbors analysis and visual enrichment.

GXD's RNA-Seq and Microarray Experiment Search: using curated metadata to reliably find mouse expression studies of interest.

The Gene Expression Database (GXD), an extensive community resource of curated expression information for the mouse, has developed an RNA-Seq and Microarray Experiment Search (http://www.informatics.jax.org/gxd/htexp_index). This tool allows users to quickly and reliably find specific experiments in ArrayExpress and the Gene Expression Omnibus (GEO) that study endogenous gene expression in wild-type and mutant mice. Standardized metadata annotations, curated by GXD, allow users to specify the anatomical structure, developmental stage, mutated gene, strain and sex of samples of interest, as well as the study type and key parameters of the experiment. These searches, powered by controlled vocabularies and ontologies, can be combined with free text searching of experiment titles and descriptions. Search result summaries include link-outs to ArrayExpress and GEO, providing easy access to the expression data itself. Links to the PubMed entries for accompanying publications are also included. More information about this tool and GXD can be found at the GXD home page (http://www.informatics.jax.org/expression.shtml). Database URL: http://www.informatics.jax.org/expression.shtml.

The JAX Synteny Browser for mouse-human comparative genomics.

Visualizing regions of conserved synteny between two genomes is supported by numerous software applications. However, none of the current applications allow researchers to select genome features to display or highlight in blocks of synteny based on the annotated biological properties of the features (e.g., type, function, and/or phenotype association). To address this usability gap, we developed an interactive web-based conserved synteny browser, The Jackson Laboratory (JAX) Synteny Browser. The browser allows researchers to highlight or selectively display genome features in the reference and/or the comparison genome according to the biological attributes of the features. Although the current implementation for the browser is limited to the reference genomes for the laboratory mouse and human, the software platform is intentionally genome agnostic. The JAX Synteny Browser software can be deployed for any two genomes where genome coordinates for syntenic blocks are defined and for which biological attributes of the features in one or both genomes are available in widely used standard bioinformatics file formats. The JAX Synteny Browser is available at: http://syntenybrowser.jax.org/. The code base is available from GitHub: https://github.com/TheJacksonLaboratory/syntenybrowser and is distributed under the Creative Commons Attribution license (CC BY).

The mouse Gene Expression Database (GXD): 2019 update.

The mouse Gene Expression Database (GXD) is an extensive, well-curated community resource freely available at www.informatics.jax.org/expression.shtml. Covering all developmental stages, GXD includes data from RNA in situ hybridization, immunohistochemistry, RT-PCR, northern blot and western blot experiments in wild-type and mutant mice. GXD's gene expression information is integrated with the other data in Mouse Genome Informatics and interconnected with other databases, placing these data in the larger biological and biomedical context. Since the last report, the ability of GXD to provide insights into the molecular mechanisms of development and disease has been greatly enhanced by the addition of new data and by the implementation of new web features. These include: improvements to the Differential Gene Expression Data Search, facilitating searches for genes that have been shown to be exclusively expressed in a specified structure and/or developmental stage; an enhanced anatomy browser that now provides access to expression data and phenotype data for a given anatomical structure; direct access to the wild-type gene expression data for the tissues affected in a specific mutant; and a comparison matrix that juxtaposes tissues where a gene is normally expressed against tissues, where mutations in that gene cause abnormalities.

Mouse Genome Database (MGD) 2019.

The Mouse Genome Database (MGD; http://www.informatics.jax.org) is the community model organism genetic and genome resource for the laboratory mouse. MGD is the authoritative source for biological reference data sets related to mouse genes, gene functions, phenotypes, and mouse models of human disease. MGD is the primary outlet for official gene, allele and mouse strain nomenclature based on the guidelines set by the International Committee on Standardized Nomenclature for Mice. In this report we describe significant enhancements to MGD, including two new graphical user interfaces: (i) the Multi Genome Viewer for exploring the genomes of multiple mouse strains and (ii) the Phenotype-Gene Expression matrix which was developed in collaboration with the Gene Expression Database (GXD) and allows researchers to compare gene expression and phenotype annotations for mouse genes. Other recent improvements include enhanced efficiency of our literature curation processes and the incorporation of Transcriptional Start Site (TSS) annotations from RIKEN's FANTOM 5 initiative.

Model organism data evolving in support of translational medicine.

Model organism databases (MODs) have been collecting and integrating biomedical research data for 30 years and were designed to meet specific needs of each model organism research community. The contributions of model organism research to understanding biological systems would be hard to overstate. Modern molecular biology methods and cost reductions in nucleotide sequencing have opened avenues for direct application of model organism research to elucidating mechanisms of human diseases. Thus, the mandate for model organism research and databases has now grown to include facilitating use of these data in translational applications. Challenges in meeting this opportunity include the distribution of research data across many databases and websites, a lack of data format standards for some data types, and sustainability of scale and cost for genomic database resources like MODs. The issues of widely distributed data and application of data standards are some of the challenges addressed by FAIR (Findable, Accessible, Interoperable, and Re-usable) data principles. The Alliance of Genome Resources is now moving to address these challenges by bringing together expertly curated research data from fly, mouse, rat, worm, yeast, zebrafish, and the Gene Ontology consortium. Centralized multi-species data access, integration, and format standardization will lower the data utilization barrier in comparative genomics and translational applications and will provide a framework in which sustainable scale and cost can be addressed. This article presents a brief historical perspective on how the Alliance model organisms are complementary and how they have already contributed to understanding the etiology of human diseases. In addition, we discuss four challenges for using data from MODs in translational applications and how the Alliance is working to address them, in part by applying FAIR data principles. Ultimately, combined data from these animal models are more powerful than the sum of the parts.

Mouse Genome Database (MGD)-2018: knowledgebase for the laboratory mouse.

The Mouse Genome Database (MGD; http://www.informatics.jax.org) is the key community mouse database which supports basic, translational and computational research by providing integrated data on the genetics, genomics, and biology of the laboratory mouse. MGD serves as the source for biological reference data sets related to mouse genes, gene functions, phenotypes and disease models with an increasing emphasis on the association of these data to human biology and disease. We report here on recent enhancements to this resource, including improved access to mouse disease model and human phenotype data and enhanced relationships of mouse models to human disease.

The Mouse Tumor Biology Database: A Comprehensive Resource for Mouse Models of Human Cancer.

Research using laboratory mice has led to fundamental insights into the molecular genetic processes that govern cancer initiation, progression, and treatment response. Although thousands of scientific articles have been published about mouse models of human cancer, collating information and data for a specific model is hampered by the fact that many authors do not adhere to existing annotation standards when describing models. The interpretation of experimental results in mouse models can also be confounded when researchers do not factor in the effect of genetic background on tumor biology. The Mouse Tumor Biology (MTB) database is an expertly curated, comprehensive compendium of mouse models of human cancer. Through the enforcement of nomenclature and related annotation standards, MTB supports aggregation of data about a cancer model from diverse sources and assessment of how genetic background of a mouse strain influences the biological properties of a specific tumor type and model utility. Cancer Res; 77(21); e67-70. ©2017 AACR.

Mouse Genome Database (MGD)-2017: community knowledge resource for the laboratory mouse.

The Mouse Genome Database (MGD: http://www.informatics.jax.org) is the primary community data resource for the laboratory mouse. It provides a highly integrated and highly curated system offering a comprehensive view of current knowledge about mouse genes, genetic markers and genomic features as well as the associations of those features with sequence, phenotypes, functional and comparative information, and their relationships to human diseases. MGD continues to enhance access to these data, to extend the scope of data content and visualizations, and to provide infrastructure and user support that ensures effective and efficient use of MGD in the advancement of scientific knowledge. Here, we report on recent enhancements made to the resource and new features.

The mouse Gene Expression Database (GXD): 2017 update.

The Gene Expression Database (GXD; www.informatics.jax.org/expression.shtml) is an extensive and well-curated community resource of mouse developmental expression information. Through curation of the scientific literature and by collaborations with large-scale expression projects, GXD collects and integrates data from RNA in situ hybridization, immunohistochemistry, RT-PCR, northern blot and western blot experiments. Expression data from both wild-type and mutant mice are included. The expression data are combined with genetic and phenotypic data in Mouse Genome Informatics (MGI) and made readily accessible to many types of database searches. At present, GXD includes over 1.5 million expression results and more than 300 000 images, all annotated with detailed and standardized metadata. Since our last report in 2014, we have added a large amount of data, we have enhanced data and database infrastructure, and we have implemented many new search and display features. Interface enhancements include: a new Mouse Developmental Anatomy Browser; interactive tissue-by-developmental stage and tissue-by-gene matrix views; capabilities to filter and sort expression data summaries; a batch search utility; gene-based expression overviews; and links to expression data from other species.

Mouse Genome Informatics (MGI): Resources for Mining Mouse Genetic, Genomic, and Biological Data in Support of Primary and Translational Research.

The Mouse Genome Informatics (MGI), resource ( www.informatics.jax.org ) has existed for over 25 years, and over this time its data content, informatics infrastructure, and user interfaces and tools have undergone dramatic changes (Eppig et al., Mamm Genome 26:272-284, 2015). Change has been driven by scientific methodological advances, rapid improvements in computational software, growth in computer hardware capacity, and the ongoing collaborative nature of the mouse genomics community in building resources and sharing data. Here we present an overview of the current data content of MGI, describe its general organization, and provide examples using simple and complex searches, and tools for mining and retrieving sets of data.

Mouse genome database 2016.

The Mouse Genome Database (MGD; http://www.informatics.jax.org) is the primary community model organism database for the laboratory mouse and serves as the source for key biological reference data related to mouse genes, gene functions, phenotypes and disease models with a strong emphasis on the relationship of these data to human biology and disease. As the cost of genome-scale sequencing continues to decrease and new technologies for genome editing become widely adopted, the laboratory mouse is more important than ever as a model system for understanding the biological significance of human genetic variation and for advancing the basic research needed to support the emergence of genome-guided precision medicine. Recent enhancements to MGD include new graphical summaries of biological annotations for mouse genes, support for mobile access to the database, tools to support the annotation and analysis of sets of genes, and expanded support for comparative biology through the expansion of homology data.

The International Mouse Strain Resource (IMSR): cataloging worldwide mouse and ES cell line resources.

The availability of and access to quality genetically defined, health-status known mouse resources is critical for biomedical research. By ensuring that mice used in research experiments are biologically, genetically, and health-status equivalent, we enable knowledge transfer, hypothesis building based on multiple data streams, and experimental reproducibility based on common mouse resources (reagents). Major repositories for mouse resources have developed over time and each has significant unique resources to offer. Here we (a) describe The International Mouse Strain Resource that offers users a combined catalog of worldwide mouse resources (live, cryopreserved, embryonic stem cells), with direct access to repository sites holding resources of interest and (b) discuss the commitment to nomenclature standards among resources that remain a challenge in unifying mouse resource catalogs.

Mouse Genome Informatics (MGI): reflecting on 25 years.

From its inception in 1989, the mission of the Mouse Genome Informatics (MGI) resource remains to integrate genetic, genomic, and biological data about the laboratory mouse to facilitate the study of human health and disease. This mission is ever more feasible as the revolution in genetics knowledge, the ability to sequence genomes, and the ability to specifically manipulate mammalian genomes are now at our fingertips. Through major paradigm shifts in biological research and computer technologies, MGI has adapted and evolved to become an integral part of the larger global bioinformatics infrastructure and honed its ability to provide authoritative reference datasets used and incorporated by many other established bioinformatics resources. Here, we review some of the major changes in research approaches over that last quarter century, how these changes are reflected in the MGI resource you use today, and what may be around the next corner.

Mouse Genome Database: From sequence to phenotypes and disease models.

The Mouse Genome Database (MGD, www.informatics.jax.org) is the international scientific database for genetic, genomic, and biological data on the laboratory mouse to support the research requirements of the biomedical community. To accomplish this goal, MGD provides broad data coverage, serves as the authoritative standard for mouse nomenclature for genes, mutants, and strains, and curates and integrates many types of data from literature and electronic sources. Among the key data sets MGD supports are: the complete catalog of mouse genes and genome features, comparative homology data for mouse and vertebrate genes, the authoritative set of Gene Ontology (GO) annotations for mouse gene functions, a comprehensive catalog of mouse mutations and their phenotypes, and a curated compendium of mouse models of human diseases. Here, we describe the data acquisition process, specifics about MGD's key data areas, methods to access and query MGD data, and outreach and user help facilities.