The Integration of Trans-omics for Precision Medicine (TOPMED) and Other Heart, Lung, Blood and Sleep (HLBS) Data Sets with the Data Commons

生命科学正处于一场数据革命之中。廉价和准确的基因组测序成为现实，高分辨率成像正在成为例行公事，临床数据越来越多地以机器可读的格式存储。这些突破将我们带入了生物医学的新纪元，在这个时代，数据科学具有推动我们对人类疾病的理解和治疗的潜力。然而，要实现这一潜力，将需要创建能够支持无限规模存储、共享和分析数据的软件平台。在此应用程序中，我们建议通过将芝加哥大学、布罗德研究所和加州大学圣克鲁斯分校这三个小组聚集在一起来解决这一未得到满足的需求，每个小组都在开发生产级软件平台以支持旗舰科学工作方面有着良好的记录，包括All Us Cohort计划、基因组数据共享(GDC)及其附属的NCI Cloud Pilots计划，以及人类细胞图谱数据协调平台(HCA DCP)。我们的目标是协调和整合我们在构建数据平台方面的个人努力，以建立一个能够服务于NIH数据公地和其他需求的紧密结合的环境。因为这些平台都是为了满足不同的用例而开发的，所以目前它们之间的互补性远远大于重叠。例如，Grossman博士在大规模运行混合云以支持GDC需求方面拥有丰富的专业知识；这在数据传输和出口方面提供了成本效益，这对NIH数据公地来说将是无价的。同样，Philippakis博士开发了基于云的协作工作空间模型(FireCloud)和用于管理二次数据使用限制(DUO)的软件，Paten博士长期以来一直是开发和实施标准化API的领导者，作为GA4GH的一部分。正是这种互补性促使我们整合我们的努力。在下面的部分中，我们将介绍我们创建公共资源联盟平台的计划。除了对所需内容有统一的技术愿景外，我们还围绕一套核心指导原则达成一致：(1)开源--我们开发的所有软件，从用户界面到云金属，都是开源的。这不仅包括将通过该奖励机制提供资金的软件，还包括我们团队开发和部署的所有软件。(2)模块化和可互操作--所有复杂软件项目的设计原则都是“关注点分离”，即在体系结构组件之间应该有一个清晰的划分，每个组件都由定义良好的接口封装。我们致力于构建模块化和可互操作的软件，并在这样做的同时，鼓励围绕它们创建一个生态系统。(3)标准驱动-我们的团队致力于创建和利用标准化的API和数据格式。自GA4GH成立以来，我们一直是GA4GH的领导者，主持各种工作组和司机项目。(4)良性竞争-我们联盟的理念是在API上进行合作以支持互操作性，但在实施上进行竞争以鼓励创造力和多样性。(5)数据类型的多样性-我们在分子图谱以外的多种数据类型方面拥有专业知识。特别是，我们所有人的一个关键目标是以参与者提供的数据和医疗记录的形式收集广泛的临床数据。同样，通过脑健康共享中心，格罗斯曼博士将管理临床和影像数据。随着公地扩展到包括其他数据类型，这些功能将是无价的。(6)在科学用例的推动下-我们的联盟包括许多领先的科学家，包括模式生物数据库、GTEx和TOPMed奖项的PI。我们将通过推动使用案例来利用他们的洞察力，以确保我们的软件能够实现旗舰科学调查。

The life sciences are in the midst of a data revolution. Cheap and accurate genome sequencing is a reality, high-resolution imaging is becoming routine, and clinical data is increasingly stored in machine-readable formats. These breakthroughs have brought us to the threshold of a new era in biomedicine, one where the data sciences hold the potential to propel our understanding and treatment of human disease. Achieving this potential, however, will require creating software platforms that can support storing, sharing, and analyzing data at unlimited scale. In this application, we propose to address this unmet need by bringing together three groups — the University of Chicago, the Broad Institute, and the University of California at Santa Cruz — each with a strong track record of developing production-grade software platforms to support flagship scientific efforts, including the All of Us Cohort Program, the Genome Data Commons (GDC) and its affiliated NCI Cloud Pilots program, and the Human Cell Atlas Data Coordination Platform (HCA DCP). Our goal is to align and integrate our individual efforts at building data platforms, in order to build a cohesive environment that can serve the needs of the NIH Data Commons and beyond. Because these platforms were each developed to fulfill differing use cases, there is currently far more complementarity than overlap between them. For example, Dr. Grossman has extensive expertise in running a hybrid cloud at scale to support the needs of the GDC; this provides cost benefits around data transport and egress that would be invaluable to the NIH Data Commons. Similarly, Dr. Philippakis has developed a cloud-based model of collaborative workspaces (FireCloud) and software for management of secondary data use restrictions (DUOS), and Dr. Paten has long been a leader in developing and implementing standardized APIs as part of the GA4GH. It is this complementarity that motivates us to integrate our efforts. In the sections below, we present our plans for creating the Commons Alliance Platform. In addition to having a unified technical vision for what is needed, we are also aligned around a core set of guiding principles: (1) Open-source - All the software we develop, from user interfaces down to cloud metal, is open-source. This includes not only the software that would be funded via this awarding mechanism, but all software developed and deployed by our team. (2) Modular and interoperable - A design principle of all complex software undertakings is “separation of concerns,” i.e. the notion that there should be a clean division between architectural components, each encapsulated by well-defined interfaces. We are committed to building modular and interoperable software and, in doing so, encouraging the creation of an ecosystem around them. (3) Standards-driven - Our team is committed to creating and utilizing standardized APIs and data formats. We have been leaders in GA4GH since its founding, chairing various working groups and driver projects. (4) Healthy Competition - Our consortium’s philosophy is to collaborate on APIs to support interoperability, but compete on implementation to encourage creativity and diversity. (5) Diversity of data types - We have expertise in multiple data types beyond molecular profiling. In particular, a key goal of All of Us is to collect extensive clinical data in the form of participant-provided data and medical records. Similarly, through the Brain Health Commons, Dr. Grossman will be managing clinical and imaging data. These capabilities will be invaluable as the Commons expands to include additional data types. (6) Driven by scientific use cases - Our consortium includes many leading scientists, including PIs on awards for model organism databases, GTEx, and TOPMed. We will leverage their insights via driving use cases to ensure that our software enables flagship scientific investigations.