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

A Catalog of Cell Types and Genomic Elements in Tissues, Organoids and Disease
组织、类器官和疾病中的细胞类型和基因组元件目录
批准号:
9810980
负责人:
BRADLEY Evan BERNSTEIN
金额:
$197.94万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2017
资助国家:
美国
项目状态:
已结题
起止时间:
2017-02-01 至 2021-01-31

项目摘要

项目成果

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中文摘要
翻译
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件。ENCODE已经建立了一个开创性的资源, 使人类生物学、遗传学和疾病研究成为可能。然而,在实现联合会的目标方面取得的进展, 鉴定所有功能性基因组元件受到适度的测定通量和以下事实的限制 功能元素往往是精致的上下文特定的,只声明自己在特定的 在特定的疾病环境中,或在被组织异质性掩盖的特定细胞类型中,可以在不同的发育间隔中观察到。 为了克服这些限制,加快实现ENCODE目标的进展,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 这些细胞可以从动物标本中提取,也可以从实验室的“类器官”模型中提取,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得全基因组染色质的多路复用管道 状态映射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 不同细胞类型中的修饰将被整合以获得一组全面的序列元件, 人类基因组,由它们的预测功能和细胞类型特异性注释。 该项目将汇集人类生物学和发育、染色质、 生物学基因组学和生产研究。该科学团队将与其他数据中心密切协调, 编码联盟的生产、协调、分析和功能表征中心, 组装一个共同的目录的位置和细胞类型特异性功能的调控元件在 人类基因组这些注释和项目中收集的所有原始数据将免费提供 科学界,目标是促进生物医学研究和推进基因组医学。
英文摘要
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.
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