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: 10240019
• 负责人: BRADLEY Evan BERNSTEIN
• 金额: $ 200.27万
• 依托单位: BROAD INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-02-01 至 2022-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10240019
• 关键词: Alzheimer' s disease pathology; Biological; Biological Assay; Brain; Catalogs; Cells; ChIP-seq; Chromatin; Data; Data Set; Disease; Elements; Encyclopedias; Funding; Genome; Genomics; Goals; Gold; Hand; Histones; Human Genome; Infrastructure; Maps; National Human Genome Research Institute; Organoids; Phase; Prefrontal Cortex; Research; Sampling; Technology; Tissues; Work; cell type; cost; operation; working group

Project Summary: NHGRI’s ENCODE Project aims to develop a comprehensive catalog of functional sequence elements in the human genome. The goal of ENCODE4 is to continue to catalyze genome research by capturing new elements and precisely defining the cell & tissue type(s) in which each element acts. To this end, the mapping centers will have amassed approximately 1000 diverse BioSamples during the main phase of ENCODE4. The prioritization of these samples for the different assays to maximize the coverage and utility of ENCODE4 has been an ongoing effort led by the BioSamples working group. By the end of the main phase of the project, our mapping center will have contributed chromatin state data (6 histone marks and CTCF) for 306 of these BioSamples. In year 5, we propose to add chromatin state data for 105 additional BioSamples. This represents an increased throughput from the main phase of the project. In addition, we will profile dorsolateral prefrontal cortex (DLPFC) from 80 brains with varying Alzheimer’s disease pathologies across year 4 and 5 as part of a distinct funding supplement. In year 5, we will continue to map chromatin state using two technologies: ChIP-seq and MINT. BioSamples have been chosen to maximize integration with other mapping centers, genomic coverage, coverage of biological space, and utility of the Encyclopedia. In summary, the consortium and our mapping center continue to work towards a holistic gold-standard dataset of candidate functional elements and their cellular contexts. To this end, the ENCODE project phase 4 has assembled a critical set of BioSamples and data. Given that critical infrastructure has been established, that our mapping center is in a phase of extremely efficient operation, and that key BioSamples are in hand, the impact of the project could be cost-effectively amplified to a great extent by completing chromatin state mapping of the highest priority information-rich BioSamples in Year 5.

项目概述：NHGRI的ENCODE项目旨在开发一个功能全面的目录， 人类基因组中的序列元件。ENCODE 4的目标是继续促进基因组研究 通过捕获新元素并精确定义每个元素作用的细胞和组织类型。本 最终，在主要阶段，制图中心将积累大约1000个不同的生物样品 编码4对这些样本进行不同检测的优先级排序，以最大限度地提高覆盖率和效用 ENCODE 4是由生物样品工作组领导的一项持续努力。在主要阶段结束时 在该项目中，我们的绘图中心将为以下项目提供染色质状态数据（6个组蛋白标记和CTCF）： 306个生物样本在第5年，我们建议增加105个额外的染色质状态数据， 生物样品。这表明项目主要阶段的生产量有所增加。此外，我们将 来自80个具有不同阿尔茨海默病病理学的脑的背外侧前额叶皮层（DLPFC）的轮廓 第四年和第五年，作为一个独特的资金补充的一部分。在第5年，我们将继续绘制染色质状态图， 使用两种技术：ChIP-seq和MINT。选择生物样品是为了最大限度地整合其他 地图中心，基因组覆盖率，生物空间覆盖率，以及百科全书的实用性。在 总而言之，联盟和我们的制图中心继续致力于建立一个完整的黄金标准数据集， 候选功能元件及其细胞背景。为此，ENCODE项目第四阶段已 收集了一组关键的生物样本和数据鉴于关键基础设施已经建立， 我们的绘图中心正处于一个非常有效的运作阶段，关键的生物样品在手， 该项目的影响可以在很大程度上通过完成染色质状态 在第5年绘制最高优先级的信息丰富的生物样品。

项目成果

A Genetic Variant Associated with Five Vascular Diseases Is a Distal Regulator of Endothelin-1 Gene Expression.

与五种血管疾病相关的遗传变异是内皮素-1基因表达的远端调节剂。

• DOI: 10.1016/j.cell.2017.06.049
• 发表时间: 2017-07-27
• 期刊: Cell
• 影响因子: 64.5
• 作者: Gupta RM;Hadaya J;Trehan A;Zekavat SM;Roselli C;Klarin D;Emdin CA;Hilvering CRE;Bianchi V;Mueller C;Khera AV;Ryan RJH;Engreitz JM;Issner R;Shoresh N;Epstein CB;de Laat W;Brown JD;Schnabel RB;Bernstein BE;Kathiresan S
• 通讯作者: Kathiresan S

Chromatin complex dependencies reveal targeting opportunities in leukemia.

• DOI: 10.1038/s41467-023-36150-7
• 发表时间: 2023-01-27
• 期刊: NATURE COMMUNICATIONS
• 影响因子: 16.6
• 作者: Najm, Fadi J.;DeWeirdt, Peter;Moore, Molly M.;Bevill, Samantha M.;El Farran, Chadi A.;Macias, Kevin A.;Hegde, Mudra;Waterbury, Amanda L.;Liau, Brian B.;van Galen, Peter;Doench, John G.;Bernstein, Bradley E.
• 通讯作者: Bernstein, Bradley E.

Analyzing histone ChIP-seq data with a bin-based probability of being signal.

• DOI: 10.1371/journal.pcbi.1011568
• 发表时间: 2023-10
• 期刊: PLoS computational biology
• 影响因子: 4.3