UK Infrastructure for Large-scale Clinical Genomics Research

英国10万基因组计划将加速全基因组测序（WGS）在国民健康服务常规护理中的应用。基因组是生物体的遗传物质（要么在DNA中，要么在RNA中，对于许多类型的病毒来说）。WGS提供了最全面的个体遗传变异清单。通过将其纳入日常护理，它将改变人们获得的卫生服务，改变诊断和管理的过程。英国10万基因组计划试图通过对受罕见疾病和癌症（及其家庭）和传染病病原体影响的个人进行10万基因组测序来推动这一变化。远景英国大规模临床基因组学研究基础设施将提供基础设施，利用100,000基因组项目的信息，将英国发展成为分析大型和复杂生物医学数据集的国际卓越中心。作为发展新知识的国家资源，它将在对疾病的起因和后果、预防和治疗的研究的速度和范围方面提供变革性的进步。这一提议为英国临床研究提供了一个独特的机会，它将使新的诊断方法得以发现，测试分层医学的复杂方法，并推动治疗创新。英国有6000到8000种罕见疾病，虽然每种疾病只影响一小部分人，但总的来说，它们影响着300万人的生活。只有50%的罕见病有现有的分子（遗传）诊断。通过10万人基因组计划的规模和对未满足需求的关注，这一基础设施将为科学创新创造重大机会，帮助解释目前尚不清楚或不确定临床意义的基因发现。从根本上说，癌症是一种遗传疾病，突变导致细胞生长失控。测序技术的临床影响已经使疾病的精确定义成为可能，揭示了癌症如何发展的见解，并帮助确定了开发治疗方法的治疗靶点。大约200个关键基因在癌症类型中的重要性是已知的，但在临床护理中只关注这些基因并不足以对大多数癌症患者产生重大影响。由于10万人基因组计划的规模，它为推动我们的理解提供了最好的机会。病原体和传染病。病原体WGS——病毒和细菌——正在被用于传染病的常规管理，提供关于传播和抗生素耐药性的信息，并为临床研究创造巨大的机会。该提案旨在资助基因组学和临床基因组学研究的数据和计算基础设施的核心硬件和软件组件，这包括改编由该领域国际领先的英国合作伙伴开发的现有软件。拟议的基础设施将在内容、技术和科学合作方面具有创新性。它将包含一系列关键治疗领域中大量患者和病原体的临床、卫生和WGS数据。这些数据将被前瞻性地收集，并将随着临床护理的定期更新而扩展。临床医生、患者、产业界和学术界均可使用，它将：鼓励并促进研究中的参与与合作，为试验招募提供平台，并提高所获得数据的深度和质量。

Background The UK 100,000 Genomes Project will accelerate the application of whole genome sequencing (WGS) into routine care for the National Health Service. The genome is the genetic material of an organism (either in DNA or, for many types of viruses, in RNA). WGS provides the most comprehensive inventory of an individual's genetic variation. By incorporating this into routine care it will transform the health services people receive, changing the processes of diagnosis and management. The UK 100,000 Genomes Project seeks to drive this change by sequencing 100,000 genomes of individuals affected by rare diseases and cancer (and their families) and infectious disease pathogens. Vision The UK Infrastructure for Large-scale Clinical Genomics Research will provide the infrastructure which, using the information from the 100,000 Genomes project, will develop the UK as an international centre of excellences for the analysis of very large and complex biomedical datasets. As a national resource for the development of new knowledge it will provide transformative advances in the speed and range of research into the causes and consequences, prevention and treatment of disease. This proposal presents a unique opportunity for UK clinical research that will enable the discovery of new diagnostics, test complex approaches to stratified medicine, and drive therapeutic innovation. Rare diseases There are between 6,000 and 8,000 rare diseases and while each one only affects a small number of people, overall they affect the lives of 3 million people in England. Only 50% of rare diseases have an existing molecular (genetic) diagnosis. Through the scale of the 100,000 Genomes Project and by having a focus on unmet need, this infrastructure will create significant opportunities for scientific innovation, helping to assist in the interpretation of genetic findings whose clinical significance is currently unknown or uncertain. CancerCancer is, fundamentally, a genetic disorder where mutations lead to uncontrolled cell growth. The clinical impact of sequencing technologies has already enabled precise definitions of disease, uncovered insights into how cancer develops and has helped identify therapeutic targets from which to develop treatments. The importance of around 200 key genes across cancer types is known but focusing only on these alone in clinical care will not be enough to significantly impact upon the majority of individuals with cancer. Due to the scale of the 100,000 Genomes Project it offers the best opportunity to drive forward our understanding. Pathogens and Infectious Disease. WGS for pathogens - both viruses and bacteria is being adopted for routine management of infectious diseases, providing information on transmission and antibiotic resistance and creating tremendous opportunities for clinical research. Output This proposal is to fund the core hardware and software components of a data and computing infrastructure for genomics and clinical genomics research, this includes adapting existing software developed by UK partners who are international leaders in this field. The proposed infrastructure will be innovative in terms of content, technology, and scientific collaboration. It will contain clinical, health, and WGS data on large numbers of patients and pathogens in a range of key therapeutic areas. The data will be collected prospectively and will be extended with regular updates from clinical care. Available to clinicians, patients, industry and academia it will: encourage and enable engagement and collaboration in research, provide a platform for trials recruitment, and increase the depth and quality of the data obtained.