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.

项目摘要 数以万计的人类基因组已被测序，但核心挑战是 是他们的诠释。基因组中的一组全面的调控事件- 调节组-需要充分利用基因组信息，但目前没有 适用于大多数临床应用和生物系统。拟建中心将 开发技术，大大提高灵敏度，速度， 理解基因组调控的全面性。发展新型 询问基因组和调节因子之间的交易的技术， 例如来自单细胞的蛋白质和非编码RNA，以及DNA中的整合变异 序列和染色质状态随时间和个体的变化。新型分子 工程和生物传感器策略被用来封装所需的复合物 将DNA转化到探针系统中，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 或两个步骤。这些技术将应用于具有基因组的临床样品 畸变，以锻炼其鲁棒性，并首次揭示表观基因组 人类疾病进展和治疗过程中的动力学。这些技术将 广泛适用于许多生物医学研究，该中心将传播 通过培训和各种方式来学习技术。

项目成果

Genetic Adaptation of Porcine Circovirus Type 1 to Cultured Porcine Kidney Cells Revealed by Single-Molecule Long-Read Sequencing Technology.

• DOI: 10.1128/genomea.01539-16
• 发表时间: 2017-02-02
• 期刊: Genome announcements
• 作者: Tombácz D;Moldován N;Balázs Z;Csabai Z;Snyder M;Boldogkői Z
• 通讯作者: Boldogkői Z

Full Genome Sequence of the Western Reserve Strain of Vaccinia Virus Determined by Third-Generation Sequencing.

• DOI: 10.1128/genomea.01570-17
• 发表时间: 2018-03-15
• 期刊: Genome announcements
• 作者: Prazsák I;Tombácz D;Szűcs A;Dénes B;Snyder M;Boldogkői Z
• 通讯作者: Boldogkői Z

Long-read sequencing of the human cytomegalovirus transcriptome with the Pacific Biosciences RSII platform.

• DOI: 10.1038/sdata.2017.194
• 发表时间: 2017-12-19
• 期刊: Scientific data
• 影响因子: 9.8
• 作者: Balázs Z;Tombácz D;Szűcs A;Snyder M;Boldogkői Z
• 通讯作者: Boldogkői Z

Association of Omics Features with Histopathology Patterns in Lung Adenocarcinoma.

• DOI: 10.1016/j.cels.2017.10.014
• 发表时间: 2017-12-27
• 期刊: Cell systems
• 影响因子: 9.3
• 作者: Yu KH;Berry GJ;Rubin DL;Ré C;Altman RB;Snyder M
• 通讯作者: Snyder M

Chromatin accessibility landscape and regulatory network of high-altitude hypoxia adaptation.

高原缺氧适应的染色质可达性景观和调控网络

• DOI: 10.1038/s41467-020-18638-8
• 发表时间: 2020-10-01
• 期刊: Nature communications
• 影响因子: 16.6
• 作者: Xin J;Zhang H;He Y;Duren Z;Bai C;Chen L;Luo X;Yan DS;Zhang C;Zhu X;Yuan Q;Feng Z;Cui C;Qi X;Ouzhuluobu;Wong WH;Wang Y;Su B
• 通讯作者: Su B