Dizeez: an online game for human gene-disease annotation

Abstract

Structured gene annotations are a foundation upon which many bioinformatics and statistical analyses are built. However the structured annotations available in public databases are a sparse representation of biological knowledge as a whole. The rate of biomedical data generation is such that centralized biocuration efforts struggle to keep up. New models for gene annotation need to be explored that expand the pace at which we are able to structure biomedical knowledge. Recently, online games have emerged as an effective way to recruit, engage and organize large numbers of volunteers to help address difficult biological challenges. For example, games have been successfully developed for protein folding (Foldit), multiple sequence alignment (Phylo) and RNA structure design (EteRNA). Here we present Dizeez, a simple online game built with the purpose of structuring knowledge of gene-disease associations. Preliminary results from game play online and at scientific conferences suggest that Dizeez is producing valid gene-disease annotations not yet present in any public database. These early results provide a basic proof of principle that online games can be successfully applied to the challenge of gene annotation. Dizeez is available at http://genegames.org.

Figure 1. Dizeez - main game interface.

Figure 2. Dizeez - game review interface.

Figure 3. Number of Gene-Disease assertions vs. number of votes, for real- and random gameplay.

The vertical axis represents the number of associations collected during game play (log scale). Red line: real gameplay. Grey bars: mean number of associations after 100 randomizations, with associated standard deviation. ‘7+’ indicates the sum of associations collected with a number of votes equal or greater than 7.

Figure 4. Concordance between Dizeez-mined associations and Disease and Gene Annotations database.

The ‘concordance ratio’ on the vertical axis is the ratio between the associations supported by DGA and the total number of associations for a given number of votes. ‘7+’ indicates the sum of associations collected with a number of votes between 7 and 11.