Model organism data evolving in support of translational medicine

Abstract

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.

Figure 1.. Disease-related journal publications using model organisms 1988–2017.

PubMed was searched for co-occurrence of “disease” or “syndrome” with each of the six current Alliance model organisms. The mouse and rat data have been divided by 20 and 10 respectively to keep the data on a similar scale with the other included organisms. The resulting publication counts per year were plotted for each model organism. Data were collected July 13, 2018.

Figure 2.. Increasing occurrence of publications involving both zebrafish and other model organisms.

PubMed searches were done for publications involving both zebrafish and each or any of the other Alliance model organisms. Z = zebrafish, M = mouse, F = fly, R = rat, W = worm, Y = yeast. Data were collected Feb. 22, 2018 at PubMed.

Figure 3.. The relationship between human diseases and associated genes in the Alliance model organism data.

A) The total count of human diseases with which each Alliance species has at least one gene associated in the Alliance human disease data set. Total associated diseases per species is shown at the top followed by a breakdown of the count of associated diseases in a selected subset of disease groups found in the Alliance disease search results. B) A drilldown into the ‘nervous system disease’ group showing a heat map of specific selected diseases and how many genes each species has associated via an “implicated_in” relationship. Data for figure A can be found in the “Disease Group” facet of the Disease category in the Alliance search results at https://www.alliancegenome.org/search?category=disease. Data for figure B can be downloaded from “nervous system disease” page at the Alliance: https://www.alliancegenome.org/disease/DOID:863. These data were collected from the Alliance website on March 5, 2018 and visualized using Tableau Professional Edition.