Gene and Chromatin Analysis Core

基因和染色质分析核心

• 批准号: 10306367
• 负责人: Li Shen
• 金额: $ 34.9万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-02-15 至 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10306367
• 关键词: ATAC-seq; Advisory Committees; Animal Model; Autopsy; Bioinformatics; Biological Assay; Brain; Brain region; Cells; ChIP-seq; Chromatin; Collaborations; Communities; Complex; DNA Methylation; Data; Data Set; Development; Drug Addiction; Ensure; Faculty; Foundations; Gene Expression; Gene Expression Profiling; Genes; Genetic Transcription; Goals; Human; Human Genome; Human Resources; Individual; Laboratories; Lead; Leadership; Logistics; Measures; Methods; Modeling; Molecular; Neuroglia; Neurons; Opiate Addiction; Program Research Project Grants; Protocols documentation; Regulation; Research; Research Personnel; Resource Sharing; Resources; Rodent; Running; Substance Use Disorder; Technology; Work; addiction; advanced analytics; analytical tool; bioinformatics infrastructure; bioinformatics tool; bisulfite sequencing; brain cell; brain reward regions; brain tissue; cell type; chromatin modification; chromosome conformation capture; data sharing; design; epigenome; epigenome editing; experimental study; genome-wide; genome-wide analysis; improved; in vivo; interest; large datasets; meetings; member; next generation sequencing; novel; reward circuitry; rodent genome; sex; sharing platform; stimulant dependence; success; tool; transcriptome; transcriptome sequencing; whole genome

PROJECT SUMMARY/ABSTRACT– GENE AND CHROMATIN ANALYSIS CORE The Gene and Chromatin Analysis Core provides the technical and bioinformatics infrastructure to optimally mine the large amount of genome-wide gene expression and chromatin data that are generated from the PPG’s work. PPG investigators lead the field in several aspects of genome-wide analyses, including pioneering these approaches to specific cell types in brain, which offers several technical challenges. We have optimized methods for several next generation sequencing approaches, including RNA-seq, ChIP-seq, ATAC- seq, HiC, and whole genome bisulfite sequencing, among others, for rodent and human brain, the latter offering an additional set of unique technical challenges. These approaches are being used increasingly to study individual cell types within a given brain reward region, in both rodent and human. The Core has established expertise in analyzing the highly complex datasets obtained, and will work on further improving the tools available. All of the genome-wide data generated by our PPG are analyzed by this Core. In parallel, the Core runs routine genome-wide assays on defined animal models, with the Animal Models Core, and thereby provides a foundation for the more specific and sophisticated measures in the individual Projects. Indeed, each Project focuses on genes that are among the most robustly regulated across rodent addiction models and human substance use disorders. As well, the Core pilots novel experimental technologies; an example is our ability to target single chromatin modifications to a single gene within a single brain region and cell type in vivo, thus providing an unparalleled level of proof to establish transcriptional mechanisms of addiction. By consolidating the analytical work and routine genome-wide analyses within a centralized Core, we ensure rigorous control over the data and facilitate comparisons of experimental findings across the four individual Projects. This consolidation also makes financial sense, since we concentrate and maximize efficient use of our expertise. Finally, the Core is responsible, with the Administrative Core, in maintaining a platform for sharing our genome-wide datasets and analytical tools across the PPG’s laboratories as well as with the scientific community and lay public at large.

项目总结/摘要-基因和染色质分析核心 基因和染色质分析核心提供技术和生物信息学基础设施， 最佳地挖掘大量的全基因组基因表达和染色质数据，这些数据是由 PPG的工作。PPG研究人员在全基因组分析的几个方面领先该领域，包括 将这些方法用于大脑中的特定细胞类型，这带来了几个技术挑战。我们有 优化的方法，用于几种下一代测序方法，包括RNA-seq，ChIP-seq，ATAC- seq、HiC和全基因组亚硫酸氢盐测序等，用于啮齿动物和人脑，后者 提供了额外的一组独特的技术挑战。这些方法越来越多地用于 研究啮齿动物和人类大脑特定奖励区域内的单个细胞类型。核心 在分析所获得的高度复杂的数据集方面建立了专门知识，并将致力于进一步改进 工具可用。我们的PPG生成的所有全基因组数据都由该核心进行分析。并行地将第 Core使用Animal Models Core对定义的动物模型进行常规全基因组分析，从而 为个别项目中更具体和复杂的措施提供了基础。事实上，每个 该项目的重点是在啮齿动物成瘾模型中受到最有力调控的基因， 人类物质使用障碍此外，核心飞行员新颖的实验技术;一个例子是我们的 能够在体内将单个染色质修饰靶向单个脑区域和细胞类型内的单个基因， 从而为建立成瘾的转录机制提供了无与伦比的证据。通过 将分析工作和常规全基因组分析整合到一个集中的核心中，我们确保 严格控制数据，便于比较四个个体的实验结果 项目这种整合也具有财务意义，因为我们集中并最大限度地有效利用 我们的专业知识最后，核心与行政核心一起负责维持一个平台， 在PPG的实验室之间以及与 科学界和广大公众。