FlyBase portals to human disease research using Drosophila models

Abstract

The use of Drosophila melanogaster as a model for studying human disease is well established, reflected by the steady increase in both the number and proportion of fly papers describing human disease models in recent years. In this article, we highlight recent efforts to improve the availability and accessibility of the disease model information in FlyBase (http://flybase.org), the model organism database for Drosophila. FlyBase has recently introduced Human Disease Model Reports, each of which presents background information on a specific disease, a tabulation of related disease subtypes, and summaries of experimental data and results using fruit flies. Integrated presentations of relevant data and reagents described in other sections of FlyBase are incorporated into these reports, which are specifically designed to be accessible to non-fly researchers in order to promote collaboration across model organism communities working in translational science. Another key component of disease model information in FlyBase is that data are collected in a consistent format --- using the evolving Disease Ontology (an open-source standardized ontology for human-disease-associated biomedical data) - to allow robust and intuitive searches. To facilitate this, FlyBase has developed a dedicated tool for querying and navigating relevant data, which include mutations that model a disease and any associated interacting modifiers. In this article, we describe how data related to fly models of human disease are presented in individual Gene Reports and in the Human Disease Model Reports. Finally, we discuss search strategies and new query tools that are available to access the disease model data in FlyBase.

Keywords: Disease model; Drosophila; FlyBase; Online resource.

Fig. 1.

The Human Disease Model Report for amyotrophic lateral sclerosis 10 (ALS10). Selected sections of the report, as it appeared in September 2015, are shown. (A) General Information; (B) Overview; (C) Disease Summary Information; (D) Related Diseases; (E) Ortholog Information; (F) D. melanogaster Gene Information; and (G) Experimental Findings. Major section headings are indicated on the dark blue bars and in the floating ‘Report Sections’ panel (top right and bottom right). Initially, most sections are closed (as indicated by the ‘+’ icons in B) and can be opened individually. Panels C-G show selected sections that have been opened; these sections have been offset and truncated in this view. See the main text for detailed descriptions of specific sections. Note that FlyBase full gene symbols include a prefix that indicates species, ‘Hsap’ for Homo sapiens and ‘Dmel’ for Drosophila melanogaster. These are frequently used in the free text portions of the disease reports to avoid confusion because experiments often involve genes from both species.

Fig. 2.

Key disease-relevant sections in FlyBase Gene Reports. Sections of the Gene Report for the D. melanogaster TBPH gene are shown. The ‘Human Orthologs’ table (A) contains a list of the orthologous human gene(s) as computed by the OrthoDB database. Links to the OMIM and HUGO Gene Nomenclature Committee (HGNC) (Gray et al., 2015) entries for each human gene are provided along with links to the OMIM phenotype descriptions of disease(s) that the human gene has been implicated in. These links are computed from information downloaded from the HGNC and OMIM databases. The ‘Human Disease Model Data’ section (B) reports published fly models of human disease (‘Models’ table), and alleles that have been shown to modify the phenotype of these models (‘Interactions’ table). In addition, a link to the relevant FlyBase integrated Human Disease Model Report is provided (arrow) where one exists. Clicking on an allele symbol takes the user to the appropriate Allele Report, where a more detailed description of the phenotype and a list of available stocks can be found. Clicking on a disease name takes the user to a Term Report for that disease.

Fig. 3.

The Term Report for amyotrophic lateral sclerosis (ALS), based on the Disease Ontology (DO). The ‘Annotations’ section (A) provides links to genes and alleles that have been used to model the disease or interact with a model of this disease, and to FlyBase Human Disease Model Reports associated with this term. Users can choose to retrieve genes, alleles or diseases labeled with this disease term plus any of its ‘children’ terms (arrowed), or if they are interested only in data labeled with this exact term, they can click on one of the links in the ‘Data Class’ or ‘Full annotation statements’ tables. In each case, the links take the user to a hit list of the relevant genes, alleles or diseases, from which more detailed information can be obtained. The ‘Spanning Tree’ (B) indicates the position of the term in the DO hierarchy, and can be used to explore related disease terms. The current term is highlighted in black and the number to the right of it in green indicates the number of genes, alleles and diseases annotated with that term or one of its children (rec.=records).