ZFIN Research Articles

Developmental Anatomy Ontology of Zebrafish: an Integrative semantic framework

Summary Integration of information is quintessential to make use of the wealth of bioinformatics resources. One aspect of integration is to make databases interoperable through well annotated information. With new databases one strives to store complementary information and such results in collections of heterogeneous information systems. Concepts in these databases need to be connected and ontologies typically provide a common terminology to share information among different resources.Our focus of research is the zebrafish and we have developed several information systems in which ontologies are crucial. Pivot is an ontology describing the developmental anatomy, referred to as the Developmental Anatomy Ontolgoy of Zebrafish (DAOZ). The anatomical and temporal concepts are provided by the Zebrafish Information Network (ZFIN) and proven within the research community. We have constructed a 3D digital atlas of zebrafish development based on histology; the atlas is series of volumetric models; in each instance, every volume element is assigned to an anatomical term. Complementing the atlas we developed an information system with 3D patterns of gene expression in zebrafish development based on marker genes. The spatial and temporal annotations to these 3D images are drawn from the ontology that we have designed. In its design the DAOZ ontology is structured as a Directed Acyclic Graph (DAG). Such is required to find unique concept paths and prevent self referencing.As we need to address the ontology in a direct manner, the DAG structure is transferred to a database. The database is used in the integration of our databases that share concepts at different levels of aggregation. In order to make sure that sufficient levels of aggregation for applications in mind are present, the original vocabulary was enriched with more relations and concepts. Both databases can now be addressed with the same unique terms and co-occurrence and co-expression of genes can be readily extracted from the databases. Integration can be further extended to the ZFIN resource and also by including ontologies that relate to gene/gene expression (e.g. Gene Ontology). In this manner, interoperable information retrieval from heterogeneous databases can be realized. This greatly facilitates processing complex information and retrieving relations in the data through machine learning approaches.

Is your “gene of interest” interesting?

Has a large-scale screen turned up a potential gene-of-interest that you know nothing about? Your computer is a portal to a wealth of information that can save you valuable time and resources. Freely available data can help to determine whether a particular gene is worthy of further research, and what direction that research should take. Presented here are approaches to mining the Internet, including searching popular model organism databases. The primer covers two typical scenarios: the gene of interest is well characterized, or mostly uncharacterized. Also featured are interviews with Monte Westerfield, PhD, Director of the Zebrafish Information Network (ZFIN) online database, and Principal Investigator of the Human Protein Reference Database (HPRD) project, Akhilesh Pandey, MD, PhD.

Connecting evolutionary morphology to genomics using ontologies: a case study from Cypriniformes including zebrafish

One focus of developmental biology is to understand how genes regulate development, and therefore examining the phenotypic effects of gene mutation is a major emphasis in studies of zebrafish and other model organisms. Genetic change underlies alterations in evolutionary characters, or phenotype, and morphological phylogenies inferred by comparison of these characters. We will utilize both existing and new ontologies to connect the evolutionary anatomy and image database that is being developed in the Cypriniformes Tree of Life project to the Zebrafish Information Network (HYPERLINK "file://localhost/Library/Local%20Settings/Temp/zfin.org" zfin.org) database. Ontologies are controlled vocabularies that formally represent hierarchical relationships among defined biological concepts. If used to recode the free-form text descriptors of anatomical characters, evolutionary character data can become more easily computed, explored, and mined. A shared ontology for homologous modules of the phenotype must be referenced to connect the growing databases in each area in a way that evolutionary questions can be addressed. We present examples that demonstrate the broad utility of this approach.

The Zebrafish Information Network: the zebrafish model organism database

The Zebrafish Information Network (ZFIN; ) is a web based community resource that implements the curation of zebrafish genetic, genomic and developmental data. ZFIN provides an integrated representation of mutants, genes, genetic markers, mapping panels, publications and community resources such as meeting announcements and contact information. Recent enhancements to ZFIN include (i) comprehensive curation of gene expression data from the literature and from directly submitted data, (ii) increased support and annotation of the genome sequence, (iii) expanded use of ontologies to support curation and query forms, (iv) curation of morpholino data from the literature, and (v) increased versatility of gene pages, with new data types, links and analysis tools.

A role for MKP3 in axial patterning of the zebrafish embryo

Fibroblast growth factors (FGFs) are secreted molecules that can activate the RAS/mitogen-activated protein kinase (MAPK) pathway to serve crucial functions during embryogenesis. Through an in situ hybridization screen for genes with restricted expression patterns during early zebrafish development, we identified a group of genes that exhibit similar expression patterns to FGF genes. We report the characterization of zebrafish MAP kinase phosphatase 3 (MKP3; DUSP6 - Zebrafish Information Network), a member of the FGF synexpression group, showing that it has a crucial role in the specification of axial polarity in the early zebrafish embryo. MKP3 dephosphorylates the activated form of MAPK, inhibiting the RAS/MAPK arm of the FGF signaling pathway. Gain- and loss-of-function studies reveal that MKP3 is required to limit the extent of FGF/RAS/MAPK signaling in the early embryo, and that disturbing this inhibitory pathway disrupts dorsoventral patterning at the onset of gastrulation. The earliest mkp3 expression is restricted to the future dorsal region of the embryo where it is initiated by a maternal beta-catenin signal, but soon after its initiation, mkp3 expression comes under the control of FGF signaling. Thus, mkp3 encodes a feedback attenuator of the FGF pathway, the expression of which is initiated at an early stage so as to ensure correct FGF signaling levels at the time of axial patterning.

The National Institutes of Health and the Growth of the Zebrafish as an Experimental Model Organism

The National Institutes of Health (NIH), an agency in the Department of Health and Human Services (DHHS), is a strong advocate of zebrafish and other animal model systems for biomedical and behavior research. In part because of strong funding support from NIH, zebrafish research is now providing fundamental insights into physiology, behavior, and the mechanisms of human disease. Over the past few years, the NIH has established a research infrastructure for the zebrafish community that includes genomic resources and tools for genetic analysis in this system. In addition, the NIH supports community resources such as the Zebrafish International Resource Center (ZIRC) and the Zebrafish Information Network (ZFIN). With the importance of zebrafish research now well-established, NIH will continue to fund a broad array of investigator-initiated studies that focus on issues critical to human health using this model system.

WebWatch

BioTechniquesVol. 36, No. 4 WebWatchOpen AccessWebWatchKevin AhernKevin AhernSearch for more papers by this authorPublished Online:6 Jun 2018https://doi.org/10.2144/04364WW01AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinkedInRedditEmail Maximum ZoomSeeing is not only believing, it is also entertaining, and that sets the tone for the Molecular Expressions microscopy site, hosted at Florida State University. With a flair for whimsy, the site's designers provide microscopic views of unusual items, like beer and ice cream, along with standard fare, such as cell and virus structures. There's more than just fun and games, however, to be had at the site. Watch confocal microscopic images come alive with Java-based virtual viewers that provide easy viewing of slices through tissues. Learn about modern microscopic techniques, such as laser scanning confocal microscopy. You can even adjust the focus, magnification, and contrast on microscopic creatures using the popular virtual scanning electron microscope.http://micro.magnet.fsu.edu/A Full DeckRemember the days of yore when the most important thing a kid had was a collection of sports cards of favorite players filled with vital stats? Fast forward to 2004 where the card metaphor has been borrowed big time in virtual form by the Weizmann Institute of Science. Their Gene Cards, a one-stop shop for gene-disease relationships, is a collection of over 53,000 records of gene-disease links. The “statistics” on Gene Cards make the information on baseball cards look pretty paltry, with DNA sequences, chromosome location, related genes, variants, protein structure analysis, and extensive transcription data, including tissue-specific expression data from microarrays.http://bioinformatics.weizmann.ac.il/cards/Cancer AnswersThe miracles of modern medicine are comforting. Antibiotics routinely stop infections in their tracks; vaccines prevent diseases before they start; and new technologies make surgery on beating hearts almost commonplace. Is it any wonder then that diseases, such as cancer, for which medical science offers no cure, strike fear in our hearts? Where can a person diagnosed with cancer turn to for information? Ten years ago the cancer specialists at the University of Pennsylvania asked themselves the same question and then answered it promptly with OncoLink, a web resource that describes various forms of the disease, explains how treatments work, and advises on how to cope with cancer. A section entitled “Ask the Experts” also gives concerned patients an opportunity to get questions answered online.http://www.oncolink.com/Genetic AssociationsThe need for more information about disease is not restricted to patients. Each day, scientific studies report new relationships between human genes and disease, forcing even the best researchers to scramble to keep abreast of their fields. The Genetic Associations web site, hosted by the NIH's National Institute on Aging, contains a database with a bewildering array of links between diseases, gene loci, and their respective online references. Curious about a protein such as insulin? Type the term into the site's search engine and scan through the six dozen different disease records retrieved for it. After locating your disease du jour, click the View button and explore the gene/disease links to popular databases, including NCBI, PubMed, LocusLink, and HapMap.http://geneticassociationdb.nih.govCache of the DayConsider the tiny zebrafish: a simple organism that can be inexpensively raised in lab aquariums, it goes through a complete developmental cycle from fertilized eggs to miniature fish in 72 hours, and it has a transparent embryo that can easily be manipulated. Consequently, zebrafish are hotter than a fish fry when it comes to studying vertebrate development. George Streisinger at the University of Oregon popularized the zebras as models for development back in the 1970s, and today, over 300 laboratories share his vision. The Zebrafish Information Network (ZFIN) was organized in 1994 at a Cold Spring Harbor meeting to meet the needs of these scientists and today serves as an online research database. Visitors can find mutants, locate strains, download sequences, examine gene expression patterns, generate maps, and more at the ZFIN site.http://zfin.org/FiguresReferencesRelatedDetails Vol. 36, No. 4 Follow us on social media for the latest updates Metrics Downloaded 90 times History Published online 6 June 2018 Published in print April 2004 Information© 2004 Author(s)PDF download

Genetic and genomic tools for zebrafish research: The NIH zebrafish initiative

The National Institutes of Health (NIH) has been a leading advocate of the zebrafish as a model organism for the study of vertebrate development, physiology, and disease. Genomic tools, developed with the support of NIH funding, have made zebrafish even more attractive as a genetic system and have stimulated research using this model. The NIH continues to provide support for new and existing community resources, such as the Zebrafish International Resource Center and the Zebrafish Information Network, research tool development and mutant screens, and a wide array of investigator-initiated studies that are using zebrafish to elucidate many aspects of vertebrate biology.

The Zebrafish Information Network (ZFIN): the zebrafish model organism database.

The Zebrafish Information Network (ZFIN) is a web based community resource that serves as a centralized location for the curation and integration of zebrafish genetic, genomic and developmental data. ZFIN is publicly accessible at http://zfin.org. ZFIN provides an integrated representation of mutants, genes, genetic markers, mapping panels, publications and community contact data. Recent enhancements to ZFIN include: (i) an anatomical dictionary that provides a controlled vocabulary of anatomical terms, grouped by developmental stages, that may be used to annotate and query gene expression data; (ii) gene expression data; (iii) expanded support for genome sequence; (iv) gene annotation using the standardized vocabulary of Gene Ontology (GO) terms that can be used to elucidate relationships between gene products in zebrafish and other organisms; and (v) collaborations with other databases (NCBI, Sanger Institute and SWISS-PROT) to provide standardization and interconnections based on shared curation.

The Zebrafish Information Network (ZFIN): a resource for genetic, genomic and developmental research.

The Zebrafish Information Network, ZFIN, is a WWW community resource of zebrafish genetic, genomic and developmental research information (http://zfin.org). ZFIN provides an anatomical atlas and dictionary, developmental staging criteria, research methods, pathology information and a link to the ZFIN relational database (http://zfin. org/ZFIN/). The database, built on a relational, object-oriented model, provides integrated information about mutants, genes, genetic markers, mapping panels, publications and contact information for the zebrafish research community. The database is populated with curated published data, user submitted data and large dataset uploads. A broad range of data types including text, images, graphical representations and genetic maps supports the data. ZFIN incorporates links to other genomic resources that provide sequence and ortholog data. Zebrafish nomenclature guidelines and an automated registration mechanism for new names are provided. Extensive usability testing has resulted in an easy to learn and use forms interface with complex searching capabilities.

Chapter 19 Zebrafish Informatics and the ZFIN Database

The recent increase in the number of research studies using zebrafish to analyze vertebrate development and genetics has led to a significant information access problem. A concerted effort has begun to establish and maintain a centralized database for the zebrafish research community. Because of the dramatic increase in the amount of data and the need for more sophisticated search methods, the Web site information and other zebrafish research information have been integrated into a relational database called the “Zebrafish Information Network” (ZFIN). The ultimate usefulness and usability of the database depend on a careful assessment of the requirements of the users, early and continued testing of prototype interfaces by real users, and analysis of the users' interactive behavior while using the database. The data model is an abstract representational schema that defines the organization of information stored within the database. The chapter describes the data model that underlies the ZFIN database in a detailed document, which provides descriptions of the data categories defined for the database—how data are represented in the database, how data are entered and by whom, and how data are accessed through database queries.