A Catalog of Cell Types and Genomic Elements in Tissues, Organoids and Disease

项目概要 拟议项目旨在从根本上推进 ENCODE 联盟的功能目录 人类基因组中的序列元件。 ENCODE 已经建立了一个重要的资源，即 促进人类生物学、遗传学和疾病研究。然而，联盟目标的进展 识别所有功能基因组元件受到有限的检测通量和事实的限制 功能元素往往是精确地针对特定上下文的，仅在特定的情况下声明自己 发育间隔、特定疾病环境或组织异质性掩盖的特定细胞类型。 为了克服这些限制并加速实现 ENCODE 目标，拟议的项目将 从正常人体组织和血液、肿瘤和其他疾病中纯化高度特化的细胞类型 标本以及来自实验室的“类器官”模型，这些模型忠实地再现了发育中的大脑、肾脏或肠道。 这些纯化的细胞类型将应用于能够获取全基因组染色质的多重管道 状态图具有前所未有的吞吐量和低成本。数千张反映不同染色质的图谱 不同细胞类型的修饰将被整合，以衍生出一套全面的序列元素 人类基因组，通过其预测功能和细胞类型特异性进行注释。 该项目将汇集人类生物学和发育、染色质领域的多元化专家团队 生物学、基因组学和生产研究。该科学团队将与其他数据部门密切协调 编码联盟中的生产、协调、分析和功能表征中心 组装一个通用目录，其中包含调节元件的位置和细胞类型特异性功能 人类基因组。这些注释以及项目中收集的所有主要数据将免费提供 向科学界提供帮助，目标是促进生物医学研究和推进基因组医学。

Project Summary The proposed project aims to fundamentally advance the ENCODE Consortium's catalog of functional sequence elements in the human genome. ENCODE has already established a seminal resource that is enabling human biology, genetics and disease research. However, progress towards the Consortium's goal of identifying all functional genomic elements has been constrained by modest assay throughput and by the fact that functional elements tend to be exquisitely context-specific, only declaring themselves in specific developmental intervals, in specific disease settings, or in specific cell types obscured by tissue heterogeneity. To overcome these limitations and hasten progress towards ENCODE goals, the proposed project will purify highly specialized cell types from normal human tissues and blood, from tumors and other disease specimens, and from laboratory 'organoid' models that faithfully recapitulate developing brain, kidney or gut. These purified cell types will be applied to a multiplexed pipeline capable of acquiring genome-wide chromatin state maps with unprecedented throughput and low cost. Thousands of maps reflecting different chromatin modifications in different cell types will be integrated to derive a comprehensive set of sequence elements in the human genome, annotated by their predicted functions and cell type-specificities. The project will bring together a diverse team of experts in human biology and development, chromatin biology, genomics, and production research. This scientific team will coordinate closely with other Data Production, Coordination, Analysis and Functional Characterization Centers in the Encode Consortium to assemble a common catalog of the locations and cell type-specific functions of regulatory elements in the human genome. These annotations, and all primary data collected in the project, will be made freely available to the scientific community, with the goal to catalyze biomedical research and advance genomic medicine.