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 .

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.

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.

Integrating image caption information into biomedical document classification in support of biocuration.

Gathering information from the scientific literature is essential for biomedical research, as much knowledge is conveyed through publications. However, the large and rapidly increasing publication rate makes it impractical for researchers to quickly identify all and only those documents related to their interest. As such, automated biomedical document classification attracts much interest. Such classification is critical in the curation of biological databases, because biocurators must scan through a vast number of articles to identify pertinent information within documents most relevant to the database. This is a slow, labor-intensive process that can benefit from effective automation.We present a document classification scheme aiming to identify papers containing information relevant to a specific topic, among a large collection of articles, for supporting the biocuration classification task. Our framework is based on a meta-classification scheme we have introduced before; here we incorporate into it features gathered from figure captions, in addition to those obtained from titles and abstracts. We trained and tested our classifier over a large imbalanced dataset, originally curated by the Gene Expression Database (GXD). GXD collects all the gene expression information in the Mouse Genome Informatics (MGI) resource. As part of the MGI literature classification pipeline, GXD curators identify MGI-selected papers that are relevant for GXD. The dataset consists of ~60 000 documents (5469 labeled as relevant; 52 866 as irrelevant), gathered throughout 2012-2016, in which each document is represented by the text of its title, abstract and figure captions. Our classifier attains precision 0.698, recall 0.784, f-measure 0.738 and Matthews correlation coefficient 0.711, demonstrating that the proposed framework effectively addresses the high imbalance in the GXD classification task. Moreover, our classifier's performance is significantly improved by utilizing information from image captions compared to using titles and abstracts alone; this observation clearly demonstrates that image captions provide substantial information for supporting biomedical document classification and curation.Database URL.

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.

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.

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.

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.

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 (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 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.

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.

Orthology for comparative genomics in the mouse genome database.

The mouse genome database (MGD) is the model organism database component of the mouse genome informatics system at The Jackson Laboratory. MGD is the international data resource for the laboratory mouse and facilitates the use of mice in the study of human health and disease. Since its beginnings, MGD has included comparative genomics data with a particular focus on human-mouse orthology, an essential component of the use of mouse as a model organism. Over the past 25 years, novel algorithms and addition of orthologs from other model organisms have enriched comparative genomics in MGD data, extending the use of orthology data to support the laboratory mouse as a model of human biology. Here, we describe current comparative data in MGD and review the history and refinement of orthology representation in this resource.

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.

The mouse gene expression database: New features and how to use them effectively.

The Gene Expression Database (GXD) is an extensive and freely available community resource of mouse developmental expression data. GXD curates and integrates expression data from the literature, via electronic data submissions, and by collaborations with large-scale projects. As an integral component of the Mouse Genome Informatics Resource, GXD combines expression data with genetic, functional, phenotypic, and disease-related data, and provides tools for the research community to search for and analyze expression data in this larger context. Recent enhancements include: an interactive browser to navigate the mouse developmental anatomy and find expression data for specific anatomical structures; the capability to search for expression data of genes located in specific genomic regions, supporting the identification of disease candidate genes; a summary displaying all the expression images that meet specified search criteria; interactive matrix views that provide overviews of spatio-temporal expression patterns (Tissue × Stage Matrix) and enable the comparison of expression patterns between genes (Tissue × Gene Matrix); data zoom and filter utilities to iteratively refine summary displays and data sets; and gene-based links to expression data from other model organisms, such as chicken, Xenopus, and zebrafish, fostering comparative expression analysis for species that are highly relevant for developmental research.

GXD: a community resource of mouse Gene Expression Data.

The Gene Expression Database (GXD) is an extensive, easily searchable, and freely available database of mouse gene expression information (www.informatics.jax.org/expression.shtml). GXD was developed to foster progress toward understanding the molecular basis of human development and disease. GXD contains information about when and where genes are expressed in different tissues in the mouse, especially during the embryonic period. GXD collects different types of expression data from wild-type and mutant mice, including RNA in situ hybridization, immunohistochemistry, RT-PCR, and northern and western blot results. The GXD curators read the scientific literature and enter the expression data from those papers into the database. GXD also acquires expression data directly from researchers, including groups doing large-scale expression studies. GXD currently contains nearly 1.5 million expression results for over 13,900 genes. In addition, it has over 265,000 images of expression data, allowing users to retrieve the primary data and interpret it themselves. By being an integral part of the larger Mouse Genome Informatics (MGI) resource, GXD's expression data are combined with other genetic, functional, phenotypic, and disease-oriented data. This allows GXD to provide tools for researchers to evaluate expression data in the larger context, search by a wide variety of biologically and biomedically relevant parameters, and discover new data connections to help in the design of new experiments. Thus, GXD can provide researchers with critical insights into the functions of genes and the molecular mechanisms of development, differentiation, and disease.

The Mouse Genome Database (MGD): facilitating mouse as a model for human biology and disease.

The Mouse Genome Database (MGD, http://www.informatics.jax.org) serves the international biomedical research community as the central resource for integrated genomic, genetic and biological data on the laboratory mouse. To facilitate use of mouse as a model in translational studies, MGD maintains a core of high-quality curated data and integrates experimentally and computationally generated data sets. MGD maintains a unified catalog of genes and genome features, including functional RNAs, QTL and phenotypic loci. MGD curates and provides functional and phenotype annotations for mouse genes using the Gene Ontology and Mammalian Phenotype Ontology. MGD integrates phenotype data and associates mouse genotypes to human diseases, providing critical mouse-human relationships and access to repositories holding mouse models. MGD is the authoritative source of nomenclature for genes, genome features, alleles and strains following guidelines of the International Committee on Standardized Genetic Nomenclature for Mice. A new addition to MGD, the Human-Mouse: Disease Connection, allows users to explore gene-phenotype-disease relationships between human and mouse. MGD has also updated search paradigms for phenotypic allele attributes, incorporated incidental mutation data, added a module for display and exploration of genes and microRNA interactions and adopted the JBrowse genome browser. MGD resources are freely available to the scientific community.

The gene expression database for mouse development (GXD): putting developmental expression information at your fingertips.

Because molecular mechanisms of development are extraordinarily complex, the understanding of these processes requires the integration of pertinent research data. Using the Gene Expression Database for Mouse Development (GXD) as an example, we illustrate the progress made toward this goal, and discuss relevant issues that apply to developmental databases and developmental research in general. Since its first release in 1998, GXD has served the scientific community by integrating multiple types of expression data from publications and electronic submissions and by making these data freely and widely available. Focusing on endogenous gene expression in wild-type and mutant mice and covering data from RNA in situ hybridization, in situ reporter (knock-in), immunohistochemistry, reverse transcriptase-polymerase chain reaction, Northern blot, and Western blot experiments, the database has grown tremendously over the years in terms of data content and search utilities. Currently, GXD includes over 1.4 million annotated expression results and over 260,000 images. All these data and images are readily accessible to many types of database searches. Here we describe the data and search tools of GXD; explain how to use the database most effectively; discuss how we acquire, curate, and integrate developmental expression information; and describe how the research community can help in this process.