A Platform for Large-Scale Genomic Discovery

在过去的四年里，一个显着的测序技术爆炸发生了，开放 许多生物实验和发现的新途径。我们描述了一个大型平台- 大规模测序和分析，扩展了下一代 测序将改变生物医学研究，并对医疗实践产生重大影响。我们的八 具体目标交织在六个主要研究领域中，这些研究领域总体上解决了NHGRI问题 使命，并提供一个跨学科的方法，已经产生医学相关 在癌症基因组学、遗传性疾病和微生物/宏基因组学领域取得成果。我们 平台为测序相关的研究项目提供了一致的成本效益方法， 我们已经建立了一个可扩展的输入样本管道，可以接收和跟踪> 40，000 我们每年都会将一批样本导入灵活、创新的测序管道。同样可扩展的还有我们的 LIMS和分析管道能力，建立了处理多个 仅去年一年，就有数百例癌症病例通过全基因组测序和分析， 沿着与多个其他项目类型。我们描述了一个研究计划，将进一步我们的 对人类健康和疾病的探索，比以往任何时候都更加全面， 并将研究第三代测序技术， 并将它们整合到我们的制作曲目中。我们拟议工作的一个重要方面是 包括努力开始将我们的发现和程序转化为临床环境， 有效地为基因组诊断和个性化医疗奠定了基础。这一重要 将DNA测序带到临床医学需要过渡，我们的创新 测序技术、数据分析和优秀临床合作者的结合 增加成功的可能性。总的来说，我们对基因组的未来充满热情 我们将联合收割机多年来在DNA测序和分析领域的成功经验 具备必要的协作专业知识、基础设施支持以及与NHGRI的共同愿景 在未来四年内，在这些目标上取得重大进展。

Over the past four years, a remarkable sequencing technology explosion has occurred, opening many new avenues of biological experimentation and discovery. We describe a platform for large- scale sequencing and analysis that extends the incredible potential of next-generation sequencing to transform biomedical research and significantly impact medical practice. Our eight specific aims are intertwined across six major research areas that overall address the NHGRI mission and provide an interdisciplinary approach that is already producing medically relevant results in the areas of cancer genomics, heritable disease, and microbial/metagenomics. Our platform offers a consistently cost-effective approach to sequencing-related research projects and we have established a scalable incoming sample pipeline that can intake and track >40,000 samples per year into a flexible and innovative sequencing pipeline. Equally scalable are our LIMS and analysis pipeline capabilities, having established systems that processed several hundred cancer cases through whole genome sequencing and analysis in the last year alone, along with multiple other project types. We describe a research plan that will further our explorations of human health and disease, in a more comprehensive manner than ever before, and will investigate third-generation sequencing technologies, incorporating their unique attributes and integrating them to our production repertoire. One important aspect of our proposed work includes efforts to begin translating our discoveries and procedures into the clinical setting, effectively setting the stage for genomic diagnosis and personalized medicine. This important transition will be required to bring DNA sequencing to clinical medicine, and our innovative combination of sequencing technology, data analysis, and outstanding clinical collaborators increase the potential for success. Overall, we are enthusiastic about the future of genome sequencing at high scale, and we combine years of success in DNA sequencing and analysis with the necessary collaboration expertise, infrastructure support, and shared vision with NHGRI to make significant progress on these aims in the next four years.