PharmGKB: pharmacogenomics discovery and implementation

7.项目摘要 药物基因组学研究遗传变异如何影响药物反应表型， 精准医疗-在正确的时间和剂量为正确的患者选择正确的药物。一种公共资源 药物基因组学信息是至关重要的-既催化基本发现的分子机制 这推动了药物反应的变异性，并支持临床研究的实施，以了解如何 以在临床上最好地提供药物基因组学。药物基因组学知识库（PharmGKB）是 药物基因组学信息的首要公共知识库。PharmGKB策展人专注于高品质 在原始文献中提取和表示知识，并捕获有关个人的信息 影响药物反应的遗传变异，这些变异的潜在临床影响， 药物反应的药代动力学和药效学途径， 法规文件（标签）和基因组驱动处方指南。PharmGKB网站托管 每月超过60，000次独特的IP访问，并提供灵活的药物基因组学知识， 多个设备。最重要的是，PharmGKB是研究社区的中心， 药物基因组学和精确医学-将其内容与关键资源和组织相结合 包括ClinVar、ClinGen、FDA、临床药物遗传学实施联盟（CPIC）和 他人在这份提案中，我们请求支持PharmGKB作为基因组社区资源，并概述了 计划（1）从已发表文献和相关数据库中收集药物基因组学知识， 将人工策展与自动化方法相结合，以筛选重要知识，（2）构建工具， 通过提供我们的知识内容，促进药物基因组学知识的发现和使用 以对我们的用户有用的新方式建立基础，以及（3）与致力于实现基因组学的努力合作 医学，通过提供最好的科学知识来支持这些努力。

7. Project Summary Pharmacogenomics studies 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 information 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 information. 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 more than 60,000 unique IP visits per month 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, ClinGen, the FDA, the Clinical Pharmacogenetics Implementation Consortium (CPIC) and others. In this proposal, we request support for PharmGKB as a Genomic Community Resource, and outline a plan to (1) curate pharmacogenomic knowledge from the published literature and from relevant databases, combining manual curation with automated methods for triaging important knowledge, (2) build tools that catalyze the discovery and use of pharmacogenomic knowledge, by providing the content of our knowledge base in novel ways useful to our users, and (3) collaborate with efforts devoted to implementation of genomic medicine, by providing the best scientific knowledge to support these efforts.