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

项目摘要 拟议的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素。Encode已经建立了一个重要的资源，即 使人类生物学、遗传学和疾病研究成为可能。然而，朝着财团目标的进展 鉴定所有功能基因组元件一直受到适度的检测吞吐量和以下事实的限制 该功能元素往往是精致的特定于上下文的，仅在特定的 发育间期，在特定的疾病环境中，或在特定的细胞类型中，被组织异质性所掩盖。 为了克服这些限制并加速实现ENCODE目标，拟议项目将 从正常人体组织和血液、肿瘤和其他疾病中提纯高度特化的细胞类型 标本，以及来自实验室的“有机”模型，真实地概括了发育中的大脑、肾脏或肠道。 这些纯化的细胞类型将被应用于能够获得全基因组染色质的多路传输管道 具有前所未有的吞吐量和低成本的州地图。数千张反映不同染色质的地图 不同细胞类型的修饰将被整合，以推导出一套全面的序列元素 人类基因组，用它们预测的功能和细胞类型的特殊性来注释。 该项目将汇集人类生物学和发育方面的不同专家团队--染色质 生物学、基因组学和生产研究。这个科学团队将与其他数据密切协调 编码联盟中的生产、协调、分析和功能表征中心 汇编监管要素的位置和单元类型特定功能的通用目录 人类基因组。这些注解以及项目中收集的所有主要数据都将免费提供 科学界，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.