Navigating the Phenotype Frontier: The Monarch Initiative

Abstract

The principles of genetics apply across the entire tree of life. At the cellular level we share biological mechanisms with species from which we diverged millions, even billions of years ago. We can exploit this common ancestry to learn about health and disease, by analyzing DNA and protein sequences, but also through the observable outcomes of genetic differences, i.e. phenotypes. To solve challenging disease problems we need to unify the heterogeneous data that relates genomics to disease traits. Without a big-picture view of phenotypic data, many questions in genetics are difficult or impossible to answer. The Monarch Initiative (https://monarchinitiative.org) provides tools for genotype-phenotype analysis, genomic diagnostics, and precision medicine across broad areas of disease.

Keywords: comparative medicine; data integration; disease diagnosis; disease discovery; phenotype ontologies.

Figure 1

Role of phenotypes in data integration. Computable phenotypes make it possible to deeply integrate databases and infer new insights.

Figure 2

Challenges associated with integration of data using phenotypes. Published relationships are shown in solid lines. Dashed lines show relationships that require computation and/or data integration. Around the perimeter of the figure are examples of the types of questions that are difficult to answer using traditional (nonintegrative) methods. These questions are divided into “clinical,” “basic,” and “translational” research categories. Each challenge is explained in the main text of the article.

Figure 3

The Monarch Initiative’s ontology-driven data integration pipeline. Diverse data from disparate sources and annotated to disparate species-specific ontologies is integrated with unifying ontologies. The unified data corpus is used by analysis tools and interfaces.