Project Summary/Abstract Pharmacogenomics is the study of how genetic variation influences drug response phenotypes and is a pillar of precision medicine — choosing the right drug for the right patient at the right dose and time. A public resource of pharmacogenomics knowledge is critical — both to catalyze basic discovery of the molecular mechanisms that drive variability in drug response and to support the implementation of clinical research to understand how to best deliver pharmacogenomics in the clinic. The Pharmacogenomics Knowledgebase (PharmGKB) is the premier public repository of pharmacogenomics knowledge. PharmGKB curators focus on high quality extraction and representation of knowledge in the primary literature, and capture information about individual genetic variations that impact drug response, the potential clinical impact of these variations, the pharmacokinetic and pharmacodynamic pathways of drug response, the pharmacogenomic requirements in regulatory documents (labels), and guidelines for genome-driven prescribing. The PharmGKB website hosts annually on average 5.2 million webpage views (without bots) and provides flexible access to pharmacogenomics knowledge on multiple devices. Most importantly, PharmGKB serves as a hub for the research community in pharmacogenomics and precision medicine — integrating its contents with critical resources and organizations including ClinVar, the Clinical Genome Resource (ClinGen), the FDA, the Clinical Pharmacogenetics Implementation Consortium (CPIC) and others. In this proposal, we request support for PharmGKB as a Biomedical Knowledgebase, and outline a plan to (1) annotate, aggregate, integrate, and disseminate pharmacogenomic knowledge from sources utilizing community curation and semi-automated methods to assist knowledge acquisition, (2) build curation and user-specific interfaces that catalyze the discovery and use of pharmacogenomic knowledge, providing the content of our knowledgebase in novel ways that are useful to our users, (3) collaborate and integrate with ongoing national and international efforts dedicated to the implementation of genomic medicine by providing the best scientific knowledge to support these important programs and (4) develop a new long-term and conceptual framework for broadly integrating available PGx knowledgebases into genomic medicine.

Project Narrative Drug response is inherited in much the same way as other traits like height, hair color, and the risk for some diseases. Pharmacogenomics studies how human genetic (DNA) variation influences the response to drugs. The PharmGKB resource aims to catalog all the human variation that impacts drug response, so that individual genetic data can be used to choose drugs for the individual that are more likely to work, and less likely to cause side effects.