Center for Personal Dynamic Regulomes

个人动态调节中心

• 批准号: 10705043
• 负责人: Howard Y Chang
• 金额: $ 264.19万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10705043
• 关键词: Alleles; Autoimmune Diseases; Automobile Driving; Binding; Biological; Biological Assay; Biology; Biopsy; Biosensor; Blood; Brain; CRISPR interference; Cells; Chromatin; Chromosomes; Clinic; Clinical; Communities; Complex; Coupled; DNA; DNA Sequence; Data; Data Set; Dimensions; Disease; Distant; Dreams; Effectiveness; Elements; Encapsulated; Encyclopedia of DNA Elements; Engineering; Enhancers; Epigenetic Process; Epithelium; Epitopes; Etiology; Event; Exercise; Gene Expression Regulation; Generations; Genes; Genetic; Genetic Transcription; Genetic Variation; Genome; Genomics; Genotype; Heterochromatin; Human; Human Genome; Individual; Intervention; Investigation; Knowledge; Laboratories; Lead; Life; Link; Liquid substance; Malignant Neoplasms; Measurement; Methods; Modeling; Modification; Molecular; Molecular Conformation; Multiomic Data; Neurodegenerative Disorders; Organoids; Outcome; Output; Pathology; Patients; Persons; Protein Isoforms; Proteins; RNA; Regulation; Regulator Genes; Regulatory Element; Resolution; Sampling; Schizophrenia; Solid; Source; Speed; Structure; System; Technology; The Cancer Genome Atlas; Time; Tissues; Training; Untranslated RNA; Variant; biological systems; causal variant; cell type; circular RNA; clinical application; computational platform; computerized tools; connectome; disease diagnosis; epigenetic variation; epigenomics; genetic variant; genome-wide; genomic aberrations; human data; human disease; human tissue; improved; individual patient; insight; multiple omics; new technology; novel; personalized medicine; precision medicine; risk variant; sample collection; single cell technology; single molecule; transcription factor; treatment response

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.

项目概要 数以万计的人类基因组已被测序，但核心挑战 是他们对整个基因组的一套全面的调控事件的解释。 regulome——充分利用基因组信息所必需的，但目前还没有 拟议的中心将覆盖大多数临床应用和生物系统。 开发大大提高灵敏度、速度和性能的技术 我们将开发新的基因组调控的全面性。 询问基因组和监管因素之间的交易的技术， 例如来自单细胞的蛋白质和非编码 RNA，以及整合 DNA 中的变异 随着时间的推移和个体之间的序列和染色质状态。 部署工程和生物传感器策略来封装所需的复合物 将DNA转化为探针系统，使得探针系统可以直接 用于非常小的人类临床样本，并在一个样本中捕获全基因组信息 这些技术将应用于基因组临床样本。 畸变以锻炼其鲁棒性，并首次揭示表观基因组 这些技术将研究人类疾病在进展和治疗过程中的动态。 广泛适用于许多生物医学研究，中心将传播 通过培训和多种方式掌握技术。

项目成果

Atlas of Subcellular RNA Localization Revealed by APEX-Seq.

APEX-Seq 揭示的亚细胞 RNA 定位图谱。

• 发表时间: 2019-07-11
• 影响因子: 64.5
• 作者: Fazal, Furqan M;Han, Shuo;Parker, Kevin R;Kaewsapsak, Pornchai;Xu, Jin;Boettiger, Alistair N;Chang, Howard Y;Ting, Alice Y
• 通讯作者: Ting, Alice Y

Chromatin Remodeling in Response to BRCA2-Crisis.

应对 BRCA2 危机的染色质重塑。

• 发表时间: 2019
• 影响因子: 8.8
• 作者: Gruber, Joshua J;Chen, Justin;Geller, Benjamin;Jäger, Natalie;Lipchik, Andrew M;Wang, Guangwen;Kurian, Allison W;Ford, James M;Snyder, Michael P
• 通讯作者: Snyder, Michael P

c-Jun overexpression in CAR T cells induces exhaustion resistance.

CAR T 细胞中 c-Jun 过度表达可诱导疲劳抵抗。

• 发表时间: 2019
• 影响因子: 64.8
• 作者: Lynn, Rachel C;Weber, Evan W;Sotillo, Elena;Gennert, David;Xu, Peng;Good, Zinaida;Anbunathan, Hima;Lattin, John;Jones, Robert;Tieu, Victor;Nagaraja, Surya;Granja, Jeffrey;de Bourcy, Charles F A;Majzner, Robbie;Satpathy, Ansuman T;Quake, Ste
• 通讯作者: Quake, Ste

A Genetic Bottleneck of Mitochondrial DNA During Human Lymphocyte Development.

人类淋巴细胞发育过程中线粒体 DNA 的遗传瓶颈。

• 发表时间: 2022-05-03
• 影响因子: 10.7
• 作者: Tang, Zhongjie;Lu, Zhaolian;Chen, Baizhen;Zhang, Weixing;Chang, Howard Y;Hu, Zheng;Xu, Jin
• 通讯作者: Xu, Jin

HiChIPdb: a comprehensive database of HiChIP regulatory interactions.

HiChIPdb：HiChIP 监管相互作用的综合数据库。

• 发表时间: 2023-01-06
• 影响因子: 14.9
• 作者: Zeng, Wanwen;Liu, Qiao;Yin, Qijin;Jiang, Rui;Wong, Wing Hung
• 通讯作者: Wong, Wing Hung