Scalable tools to effectively translate genomic discoveries into the clinic

项目总结 我们正处于一场基因组革命中；超过25万个人类基因组已经被测序， 产生超过1 PB的基因组数据。虽然这些新数据很有希望影响健康，但有 是基因组发现和临床护理之间的脱节。供应商经常曲解基因组 信息，患者往往不了解他们自己的检测结果，以及关于疾病风险的基因组信息 很少在患者和家人之间共享。重要的是，通信和数据效率低下 误解会带来毁灭性的后果--包括不必要的器官切除、漏诊疾病 预防机会和过早死亡。 我们正在通过开发和测试优化集成的工具来解决这些基因组护理缺口 全外显子组和全基因组测序(WES，WGS)用于一般临床实践。我的愿景是 改进基因组医学是基于我在多学科联盟的工作，并向国家 人类基因组研究所提高医疗保健有效性的优先研究领域。在 拟议的工作，我们将测试癌症多水平基因组电子健康干预的有效性(目标1)。 我们的干预措施1)教育医生和患者关于基因组学，2)使患者能够直接返回 结果，3)为医生提供特定于患者的结果和用于解释的资源，以及4)促进 在家庭内部共享基因组结果。我们假设，干预措施的使用将导致更高的 接受高质量的、基因引导的护理。我们将在一项随机对照试验中检验我们的假设 在为他们的病人使用WES的学术和社区医生中。接下来，我们将使用迭代 在利益相关者的参与下，调整和试行测试我们的西班牙语和普通话工具 患者和患有糖尿病的患者(目标2)。最后，我们将创建和评估新的、适度的、社交的 网络作为基因组信息共享的平台(目标3)。我们的假设是提供者、患者和 家庭成员将参与基因组信息共享的社交网络，并发现他们高度 很有用。我们的总体方法包括1)创建安全的社交网络，2)将网络整合到 我们的电子健康干预，以及3)使用辅助方法，如访谈和自然语言 处理，评估利益相关者的网络相关态度和网络信息质量。如果成功，我们将 将处于有利地位，可以广泛传播我们的电子健康工具。总而言之，这项工作将改变 人们在临床护理的背景下获取、处理和共享基因组信息。我们的工具协调一致 基因通信允许信息的多方向流动，将多个利益相关者与 并整合高质量、动态的基于网络的资源，以改善基因组护理。在创作中 并部署既能响应并充分利用我们信息环境的复杂性的工具，我们 意在改变基因组研究和临床实践。

PROJECT SUMMARY We are in the midst of a genomic revolution; more than 250,000 human genomes have been sequenced, generating over a petabase of genomic data. While these new data hold great promise to impact health, there is a disconnect between genomic discovery and clinical care. Providers frequently misinterpret genomic information, patients often don't understand their own test results, and genomic information about disease risk is infrequently shared between patients and family members. Importantly, ineffective communication and data misinterpretation has devastating consequences- including unnecessary organ removal, missed disease prevention opportunities, and premature death. We are addressing these genomic care gaps by developing and testing tools that optimize the integration of whole-exome and whole-genome sequencing (WES, WGS) for general clinical practice. My vision for improving genomic medicine is based on my work within multidisciplinary consortia and addresses the National Human Genome Research Institute's priority research area of improving the effectiveness of healthcare. In the proposed work we will test the effectiveness of a multilevel genomic e-Health intervention in cancer (Aim 1). Our intervention 1) educates physicians and patients about genomics, 2) enables direct-to-patient return-of- results, 3) provides physicians with patient-specific results and resources for interpretation, and 4) facilitates sharing of genomic results within families. We hypothesize that intervention use will result in higher rates of uptake of high-quality, genetically guided care. We will test our hypothesis in a randomized controlled trial among academic and community physicians who use WES for their patients. Next, we will use an iterative process, with stakeholder engagement, to adapt and pilot test our tool for Spanish and Mandarin speaking patients and for patients who have diabetes (Aim 2). Finally, we will create and assess new, moderated, social networks as a platform for genomic information sharing (Aim 3). Our hypothesis is that providers, patients and family members will engage with the genomic information sharing social networks and find them to be highly useful. Our general approach includes 1) creating the secure social networks, 2) integrating the networks into our e-Health intervention, and 3) using complementary methods, such as interviews and natural language processing, to assess stakeholders' network-related attitudes and network information quality. If successful, we will be well positioned to widely disseminate our e-Health tools. In sum, this work stands to transform how people obtain, process and share genomic information in the context of clinical care. Our tools reconceive genetic communication to allow for multi-directional flow of information, connects multiple stakeholders with one another, and integrates high-quality dynamic web-based resources to improve genomic care. In creating and deploying tools that both respond to and leverage the complexities of our information environment, we intend to transform genomic research and clinical practice.