Disease Annotations for Variants in Personal Genomes

DESCRIPTION (provided by applicant): High-throughput sequencing technologies are beginning to deliver complete individual genome sequences. However, significant barriers still obstruct the use of these data for basic research and in clinical evaluation for personalized medicine. One major barrier is the absence of tools for variant annotation with respect to disease. Our goal is to overcome this barrier by creating for sequence variants a suite of tools similar to those that exist for gene annotation. Although disease, gene and sequence ontolgies already exist, systematically interrelating (harmonizing) them to one another in a manner that will support effective variant annotation is a major task. We will use state of the art protocol for biomedical ontology development, ensuring interoperability and usability to achieve this goal. The research proposed in this application has three aims. In Phase I we will harmonize and interrelate existing ontologies for variant and disease annotation, with a specific focus on cardiovascular disease (CVD). In Aim 2 we will curate an existing CVD gene collection compiled at Omicia Inc. consisting of 336 CVD disease genes to the harmonized ontology. In Aim 3 we will annotate the variants and implications of each variation for ten personal genomes. Our plan is to begin with a proof-of-concept project to develop an ontology for annotating personal sequence variants in genes implicated in CVD. In phase II we intend to expand the ontology to a broader coverage of disease, utilizing the lessons we learn from phase I. This firm logical foundation will allow us to build a suite of commercial strength software for variant annotation to provide a much needed tool for personal genomics. PUBLIC HEALTH RELEVANCE: This project will produce a modular, harmonized ontology for the description of personal genomic sequence variants with respect to cardiovascular disease (CVD). This will in turn provide a means to generate detailed, clinically relevant genetic-signature reports. This work will be preformed in partnership with Omicia Incorporated. Omicia's goal is to provide content and analysis tools for molecular diagnostic tests using personal genome sequences. The tools produced by this project will promote better public health and provide significant commercial opportunities.