Core B - Epigenomics Core

核心 B - 表观基因组学核心

• 批准号: 10154463
• 负责人: Joseph R Ecker
• 金额: $ 16.33万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-12-01 至 2025-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10154463
• 关键词: 3-Dimensional; Adopted; Algorithms; Anatomy; Animals; Anterior; Area; BRAIN initiative; Bioinformatics; California; Candidate Disease Gene; Carbon; Cells; Chromatin; Classification; Code; Complex; Cytosine; DNA Methylation; DNA Sequence Alteration; DNA methylation profiling; Data; Data Set; Development; Dimensions; Dorsal; Epigenetic Process; Exposure to; Folic Acid; Funding; Gene Expression Regulation; Generations; Genes; Genetic; Genetic Transcription; Genome; Genomics; Global Change; Goals; Human; Individual; Informatics; Institutes; International; Lateral; Measures; Medial; Meningomyelocele; Methodology; Methods; Modification; Molecular Conformation; Mus; Mutate; Mutation; Neural tube; Neuroglia; Neurons; Pathway interactions; Patients; Pattern; Phenotype; Post-Translational Protein Processing; Procedures; Production; Productivity; Publishing; Recording of previous events; Regenerative Medicine; Regulator Genes; Regulatory Element; Risk; Techniques; Technology; Tissues; United States National Institutes of Health; Untranslated RNA; Ursidae Family; Validation; Variant; Work; Xenopus; base; bisulfite sequencing; candidate marker; cell type; computerized data processing; cost effective; data sharing; epigenetic profiling; epigenome; epigenomics; gene environment interaction; genetic variant; genome-wide; histone modification; innovation; knockout animal; methylome; multimodality; multiple omics; programs; relating to nervous system; single cell analysis; single cell sequencing; success; synergism; transcriptome; whole genome

PROJECT SUMMARY – Core B: Epigenomics The epigenetic modifications found in chromatin (DNA methylation and post-translational modifications of histones) are involved in gene regulation during development and differentiation. Core B will generate epigenomics data from massive parallel, multi-omic sequencing from human and mouse and xenopus developing neural tube. The Core will identify gene regulatory elements and epigenomic variants having the potential to cause or influence phenotypes. The Program PI and Director of Core B have worked together extensively in the past with great success producing significant mouse neural tube epigenomic data. Dr. Ecker has worked broadly in the area of genomics and epigenomics and in the development methodologies employing multi-modal ‘multi-omics’ techniques for generation multiple types of NGS datasets from single cells. The data generated from Core B, as well as imported from Project I, II and III, will be delivered to Core C for extraction of results which will be delivered to each of the Projects for further validation. These goals will be accomplished by developing the key pipelines of Core B that involve data production, and analysis: 1] Bulk whole genome bisulfite sequencing (WGBS) Pipeline. The Ecker lab published the first human methylome and thus has significant expertise in the workflow for data production. Our data workflow was established, and standard operating procedures developed and adopted, by the ENCODE project and will take advantage of the same features of our WGBS workflow that has made it successful for that effort. 2] Single cell methylome sequencing (snmC-seq) pipeline. The methods for production and analysis of single cell methylome data snmC-seq2 and more recently snmC-seq3, were established and standard operating procedures develop for the NIH BRAIN initiative. 3] Multi-omics analysis combining two different NGS datasets measured from single cells. These include snMethyl-3C-seq, snPaired-seq and snMethyl-HiC. The Epigenomics Core and the Bioinformatics Core will work together to perform analysis of all epigenomic data produced by Core B, will work with existing pipelines or create new pipelines as need demands, and will share data the Projects I, II and III. We anticipate that 25,000 single cell methylomes/yr will be generated, along with detailed analyses. Data processing quantification of genome wide unmethylated and methylated cytosine base calls are generated using an algorithm that we previously developed called Methylpy. Clustering of snmC-seq2 data for cell type classification will utilize both mCG and mCH patterns to effectively classify both neuronal and non-neuronal cell types in the developing neural tube. These analyses will result in a prioritized list of candidate marker features (genes and predicted regulatory elements) that will be provided to the project PIs for further examination and validation.

项目摘要 – 核心 B：表观基因组学 染色质中发现的表观遗传修饰（DNA 甲基化和翻译后修饰） 组蛋白）参与发育和分化过程中的基因调控。 来自人类、小鼠和非洲爪蟾的大规模并行、多组学测序的表观基因组数据 发育中的神经管将识别具有以下特征的基因调控元件和表观基因组变异。 项目 PI 和核心 B 主任一起工作。 通常，Ecker 博士在过去取得了巨大的成功，产生了重要的小鼠神经管表观基因组数据。 在基因组学和表观基因组学领域以及采用 用于从单细胞数据生成多种类型 NGS 数据集的多模式“多组学”技术。 从核心 B 产生的以及从项目 I、II 和 III 进口的，将被交付到核心 C 提取 结果将交付给每个项目以供进一步验证，这些目标将通过以下方式实现。 开发涉及数据生成和分析的 Core B 关键流程：1] 批量全基因组 亚硫酸氢盐测序（WGBS）管道。埃克实验室发表了第一个人类甲基化组，因此拥有了。 我们在数据生产工作流程方面拥有丰富的专业知识，并建立了标准。 由 ENCODE 项目开发和采用的操作程序，并将利用相同的优势 我们的 WGBS 工作流程的特点使其成功实现了这一目标 2] 单细胞甲基化组。 测序 (snmC-seq) 流程用于产生和分析单细胞甲基化组数据。 snmC-seq2 和最近的 snmC-seq3 均已建立并开发了标准操作程序 NIH BRAIN 计划 3] 结合单个测量的两个不同 NGS 数据集的多组学分析。 这些包括 snMmethyl-3C-seq、snPaired-seq 和 snMmethyl-HiC。 生物信息学核心将共同对核心 B 产生的所有表观基因组数据进行分析，将发挥作用 现有管道或根据需要创建新管道，并将共享项目 I、II 和 III 的数据。 预计每年将生成 25,000 个单细胞甲基化组，并进行详细的数据处理。 使用以下方法生成全基因组非甲基化和甲基化胞嘧啶碱基的定量 我们之前开发的用于细胞类型分类的 snmC-seq2 数据聚类算法。 将利用 mCG 和 mCH 模式对神经元和非神经元细胞类型进行有效分类 这些分析将产生候选标记特征（基因和）的优先列表。 预测的监管要素）将提供给项目 PI 进行进一步检查和验证。