A Platform for Large-Scale Genomic Discovery

在过去的四年里，发生了一场引人注目的测序技术爆炸，开启了 许多生物实验和发现的新途径。我们描述了一个大型- 扩展下一代的惊人潜力的规模排序和分析 测序将改变生物医学研究并显著影响医疗实践。我们的八个人 具体目标交织在六个主要研究领域，总体上解决了NHGRI 使命，并提供一种跨学科的方法，已经产生了与医学相关的 在癌症基因组学、遗传病和微生物/元基因组学领域取得的成果。我们的 Platform为测序相关研究项目提供了一致的经济高效的方法 我们已经建立了一条可扩展的进样管道，可以采集和跟踪40,000个样品 将每年的样本送入灵活而创新的测序管道。同样可扩展的是我们的 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， 以及多个其他项目类型。我们描述了一项研究计划，该计划将推动我们的 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，结合其独特的属性 并将它们整合到我们的制作剧目中。我们拟议工作的一个重要方面 包括开始将我们的发现和程序转化为临床环境的努力， 有效地为基因组诊断和个性化医学奠定了基础。这一点很重要 将DNA测序引入临床医学将需要转型，我们的创新 结合测序技术、数据分析和杰出的临床合作者 增加成功的潜力。总体而言，我们对基因组的未来充满热情 高规模的测序，我们结合了多年在DNA测序和分析方面的成功 拥有必要的协作专业知识、基础设施支持和与NHGRI的共同愿景 在未来四年内在实现这些目标方面取得重大进展。

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.