Zebrafish Models of Human Disease: Gaining Insight into Human Disease at ZFIN

Abstract

The Zebrafish Model Organism Database (ZFIN; https://zfin.org) is the central resource for genetic, genomic, and phenotypic data for zebrafish (Danio rerio) research. ZFIN continuously assesses trends in zebrafish research, adding new data types and providing data repositories and tools that members of the research community can use to navigate data. The many research advantages and flexibility of manipulation of zebrafish have made them an increasingly attractive animal to model and study human disease.To facilitate disease-related research, ZFIN developed support to provide human disease information as well as annotation of zebrafish models of human disease. Human disease term pages at ZFIN provide information about disease names, synonyms, and references to other databases as well as a list of publications reporting studies of human diseases in which zebrafish were used. Zebrafish orthologs of human genes that are implicated in human disease etiology are routinely studied to provide an understanding of the molecular basis of disease. Therefore, a list of human genes involved in the disease with their corresponding zebrafish ortholog is displayed on the disease page, with links to additional information regarding the genes and existing mutations. Studying human disease often requires the use of models that recapitulate some or all of the pathologies observed in human diseases. Access to information regarding existing and published models can be critical, because they provide a tractable way to gain insight into the phenotypic outcomes of the disease. ZFIN annotates zebrafish models of human disease and supports retrieval of these published models by listing zebrafish models on the disease term page as well as by providing search interfaces and data download files to access the data. The improvements ZFIN has made to annotate, display, and search data related to human disease, especially zebrafish models for disease and disease-associated gene information, should be helpful to researchers and clinicians considering the use of zebrafish to study human disease.

Keywords: Danio rerio; ZFIN; database; disease; disease models; translational research; zebrafish.

Figure 1

‘zebrafish’ and ‘disease/disorder/syndrome/cancer’ words co-occur increasingly in PubMed publications. Percentage of zebrafish publications per year with the word ‘zebrafish’ and ‘disease’ is shown. The number of zebrafish publications was determined by using the words ‘zebrafish’ OR ‘zebra fish’ OR ‘Danio rerio’ in the PubMed advanced search. The amount of publications containing both zebrafish and disease words was determined by using the words ‘zebrafish’ OR ‘zebra fish’ OR ‘Danio rerio’ AND ‘disease’ OR ‘syndrome’ OR ‘disorder’ OR ‘cancer’ in the PubMed advanced search. PubMed searches were conducted September 28, 2016.

Figure 2

The ZFIN disease page displays information about the disease, human genes associated to the disease and their zebrafish orthologs, and a list of zebrafish models for this disease. Snapshot of the ZFIN disease term page for PD. (A) The information about the disease such as synonyms, definition, and references to other human disease databases come from the DO. Relationships with other terms of the ontology are also shown. (B) “Genes Involved” section shows the human genes associated to the disease based on information from OMIM. The zebrafish orthologs to these genes are displayed based on the ZFIN curated orthology. Clicking on these zebrafish genes (arrow) links to the ZFIN gene page. (C) A list of zebrafish models, defined as “Fish” in “Experimental Conditions”, is displayed in the “Zebrafish Models” section. These models are associated with citations in which they were used and/or created. Phenotype of the models can be found on the Fish page which can be reached by clicking on the Fish (open arrow). (D) Publications discussing or studying the disease are listed in the “Citations” section.

Figure 3

The ZFIN gene page displays information about available mutations and sequence targeting reagents and the phenotype associated and provides a list of diseases associated with the human ortholog. Snapshot of the gba gene page. (A,B) Mutations and sequence targeting reagents reported to alter the gene function are listed, as well as the associated phenotypes. (C) Human diseases associated to the human ortholog are also displayed, and link to the ZFIN disease term page, and the OMIM record.

Figure 4

The concept of ‘Fish’ includes information about background, genotype, and STR. Snapshot of the AB + MO1-atp13a2 Fish page. (A) Background, genotype, and STR constituting ‘Fish’ are shown at the top of page. (B) Human disease modeled by this fish is shown with the ‘Experimental Conditions’ (Conditions) in which this fish would create the model. If there are gene expression annotations they are displayed under ‘Gene Expression’. (C) In the ‘Phenotype’ section, a list of phenotype annotations for the Fish and model are listed, with the corresponding citations that reported these phenotypes.

Figure 5

Human disease information can be retrieved and searched using the ZFIN search box and ZebrafishMine. (A) Single search box in ZFIN retrieves results giving information linking to the disease pages, including zebrafish models for this disease (arrow), zebrafish orthologs to the human gene involved in the disease (open arrow), and disease associated publications (arrow head). (B) ZebrafishMine search interface contains templates supporting searches of disease related information. The ZebrafishMine has predefined queries to provide human disease related data. The Gene-→OMIM Disease Phenotype search (bracket a) returns a list of OMIM disease phenotypes of the human orthologue for a given zebrafish. The OMIM Disease Phenotype → Gene search (bracket b) returns a list of zebrafish genes that are orthologous to disease related genes for a given OMIM disease.