Center for Personal Dynamic Regulomes

项目摘要 数以万计的人类基因组已经被测序，但主要的挑战是 就是他们的解释。整个基因组的一组全面的调控事件- Regulome-是充分利用基因组信息所必需的，但目前已不存在 覆盖大多数临床应用和生物系统。拟建的中心将 开发技术，大大提高敏感度、速度和 理解基因组调控的全面性。我们将开发新的 询问基因组和调节因子之间的交易的技术， 例如来自单细胞蛋白质和非编码RNA，以及DNA的整合变异 序列和染色质状态随时间和跨个体。新型分子 工程和生物传感器策略被用来封装所需的复合体 DNA转化到探针系统中，这样探针系统可以直接 在非常小的人类临床样本上使用，并在一个中捕获全基因组信息 或者两个步骤。这些技术将应用于具有基因组的临床样本 像差来锻炼它们的健壮性，并首次揭示表观基因组 人类疾病在进展和治疗过程中的动态。这些技术将 广泛适用于许多生物医学研究，该中心将传播 通过培训和多样化的手段掌握技术。

Project Summary Tens of thousands of human genomes have been sequenced, but the central challenge is their interpretation. A comprehensive set of regulatory events across a genome—the regulome—is needed to make full use of genomic information, but is currently out of reach for most clinical applications and biological systems. The proposed Center will develop technologies that greatly increase the sensitivity, speed, and comprehensiveness of understanding genome regulation. We will develop new technologies to interrogate the transactions between the genome and regulatory factors, such as proteins and noncoding RNAs from single cells, and integrate variations in DNA sequences and chromatin states over time and across individuals. Novel molecular engineering and biosensor strategies are deployed to encapsulate the desired complex DNA transformations into the probe system, such that the probe system can be directly used on very small human clinical samples and capture genome-wide information in one or two steps. These technologies will be applied to clinical samples with genomic aberrations to exercise their robustness, and reveal for the first time epigenomic dynamics of human diseases during progression and treatment. These technologies will be broadly applicable to many biomedical investigations, and the Center will disseminate the technologies via training and diverse means.