What's in a Genotype?: An Ontological Characterization for Integration of Genetic Variation Data

Exploration of the mechanistic basis of biology and disease has long leveraged the concept of a genotype, which represents the genetic composition associated with a physical trait. Translational research efforts rely increasingly on the ability to integrate genotype-phenotype data across systems and organism communities, but are hindered by the lack of a shared, computable model of the information coded into genotype representations. Here, we present the efforts of the Monarch Initiative to build GENO, an ontological model of genotype information. The Monarch Initiative is a collaborative effort to integrate data from diverse resources to leverage model systems for disease research based on their phenotypes. The genotype model we have developed is based on decomposing the different types of information represented in a genotype, is interoperable with existing OBO Foundry ontologies, and utilizes modeling from orthogonal ontologies to describe a broad range of attributes of these sequences. We describe the features and utility of such an approach toward the integration of diverse genotype data with a broad spectrum of related biomedical data.