The Zebrafish Model Organism Database: new support for human disease models, mutation details, gene expression phenotypes and searching

Abstract

The Zebrafish Model Organism Database (ZFIN; http://zfin.org) is the central resource for zebrafish (Danio rerio) genetic, genomic, phenotypic and developmental data. ZFIN curators provide expert manual curation and integration of comprehensive data involving zebrafish genes, mutants, transgenic constructs and lines, phenotypes, genotypes, gene expressions, morpholinos, TALENs, CRISPRs, antibodies, anatomical structures, models of human disease and publications. We integrate curated, directly submitted, and collaboratively generated data, making these available to zebrafish research community. Among the vertebrate model organisms, zebrafish are superbly suited for rapid generation of sequence-targeted mutant lines, characterization of phenotypes including gene expression patterns, and generation of human disease models. The recent rapid adoption of zebrafish as human disease models is making management of these data particularly important to both the research and clinical communities. Here, we describe recent enhancements to ZFIN including use of the zebrafish experimental conditions ontology, 'Fish' records in the ZFIN database, support for gene expression phenotypes, models of human disease, mutation details at the DNA, RNA and protein levels, and updates to the ZFIN single box search.

Figure 1.

The Fish concept in ZFIN. Information found at the top of a Fish page in ZFIN. Fish records include the genotype (Green; Genotype), the genetic background (Yellow, G.B.), and the sequence targeting reagents (Red, STRs) when applicable. Fish IDs have the form ZDB-FISH-######-#####. Fish ZDB-FISH-150901-11301 (https://zfin.org/ZDB-FISH-150901-11301) includes a homozygous hand2^c99/c99 gene on the AB genetic background plus three morpholinos targeting the dlx3b, dlx5a and dlx4b genes.

Figure 2.

A portion of the ZFIN gene expression curation interface. (A) portion of the ZFIN gene expression curation interface showing EaP and non-EaP expression annotations. (A) Two Expression rows, the first holding an ordinary gene expression annotation in a wild-type fish, the second row holding an EaP annotation in a mutant fish. (B) The Anatomy Pile section of the ZFIN curation interface showing the anatomical structure lateral plate mesoderm in standard format as well as expression phenotype format for lateral plate mesoderm - decreased amount. Image captured on 18 August 2016.

Figure 3.

The Phenotype Details section of the ZFIN figure page. https://zfin.org/ZDB-FIG-151214-52#expDetail shows examples of EaP and non-EaP phenotypes displayed in the Phenotype column of the Phenotype Details section for the figure. Image captured on 18 August 2016.

Figure 4.

Human disease information in ZFIN. (A) The human disease section from the atxn2 gene page showing OMIM phenotypes associated with the human ortholog of zebrafish atxn2. (B) The Disease page for Parkinson's disease showing details from the DO including disease name, synonyms, definition, cross references to other resources and term relationships within DO. The zebrafish models section shows models of this disease generated in zebrafish with chemical treatments or genetic alterations. Image captured on 24 August 2016.

Figure 5.

Single box search results. Search results for Parkinson's disease using the single box search. Categories of data matching the text search ‘Parkinson's Disease’ are in the left column along with the count of records found in that category. Image captured on 24 August 2016.

Figure 6.

Mutation details as seen on the genomic feature page and the gene page. Mutation details are displayed on the genomic feature and gene pages in ZFIN. (A) Snap shot of the b1127 point mutation feature page. The mutation details section (bracket) shows the DNA/cDNA change with the corresponding location within the gene, and the consequences at the transcript and protein level. (B) Snap shot of the fam20b gene page. The mutations available for this gene are displayed with details regarding their localization within the gene, and the transcript consequences of the mutation (bracket). Image captured on 18 August 2016.

Figure 7.

An example search in the Reporter Lines Category in ZFIN single box search interface. In this example, the Reporter Line Category was selected and values were set in the Expression Anatomy, Stage, and Reporter Gene filters to answer the question ‘Are there any reporter lines that express mCherry in Meckel's cartilage during the larval stage?’. Image captured on 24 August 2016.

Figure 8.

The single box search figure gallery. The figure gallery provides a tiled view of images associated with results of a single box search. Here, the Expression category has been searched for ‘heart’ and the ‘show images’ button was clicked to get to the figure gallery view (lower). Clicking on any figure produces a magnified view of that image (red arrow). The magnified view includes the figure caption and curated data associated with that figure. Left and Right arrows provide continued navigation through the image set in the magnified view. The particular image clicked here is Figure 1 from Lou et al. (23). Images captured on 24 August 2016.