Core C - Sequencing and Analysis.

核心 C - 排序和分析。

• 批准号: 9902360
• 负责人: Christopher A Miller
• 金额: $ 85.93万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9902360
• 关键词: AML/MDS; ATAC-seq; Acute Myelocytic Leukemia; Address; Algorithms; Aneuploidy; Bioinformatics; Biological; Biological Assay; Biological Sciences; Cells; ChIP-seq; Code; Complex; Custom; DNA; DNA sequencing; Data; Data Analyses; Data Set; Databases; Detection; Development; Disease; Disease remission; Epigenetic Process; Event; FarGo; Foundations; Functional disorder; Gene Expression Profiling; Generations; Genetic; Genome; Genomics; Goals; Heterogeneity; High Performance Computing; High-Throughput Nucleotide Sequencing; Immunogenomics; Infrastructure; Knowledge; Leadership; Link; Mediating; Methods; Methylation; Minor Histocompatibility Antigens; Modeling; Morphology; Mutation; Output; Pattern; Phase; Play; Process; Production; RNA; Relapse; Reproducibility; Resources; Role; Running; Sampling; Scientist; Sequence Alignment; Sequence Analysis; Services; Small RNA; Structure; TP53 gene; Techniques; Technology; Untranslated RNA; Validation; Variant; Visualization; allotransplant; analysis pipeline; bisulfite sequencing; clinically relevant; computer program; data management; epigenomics; exome; experience; genome sequencing; genomic biomarker; genomic platform; mouse model; nanopore; novel; response; single-cell RNA sequencing; transcriptome; transcriptome sequencing; transplant model; tumor; variant detection; whole genome

PROJECT SUMMARY/ABSTRACT The goal of Core C is to provide high-throughput production and analysis of AML genomic and epigenomic sequence data for all four projects in this PPG. This includes sequencing, somatic and germline variant detection and validation, and integration of many data types. This will be achieved by generating high-quality DNA and RNA sequencing data and analyzing it using cutting-edge algorithms and techniques. Specific Aim/Core Service 1: (Sequence Production) Sequencing of samples in Core C will take place using the Illumina HiSeqX, 4000, and NovaSeq platforms. The data produced in Core C will be comprehensive: whole genome, exome, and capture validation for DNA, as well as error-corrected sequencing, single-cell RNA-seq, total and small RNA-seq, whole genome bisulfite sequencing, and other custom epigenetic analyses. These data will be processed through state-of-the-art genomic pipelines to produce primary results like sequence alignments and variant calls. Specific Aim/Core Service 2: (Bioinformatic Analysis) These pipelines provide a starting point for the detailed, novel, and iterative analyses which will take place in Core C and are foundational for each project. Project 1 will require integrative analysis of genomic and epigenomic (transcriptome, scRNA-Seq, WGBS) data to better define the events that drive initiation, progression, and relapse in samples with and without DNMT3A mutations. In Project 2, we will leverage our experience in immunogenomics to define minor histocompatibility antigens that mediate allo-transplant response, and characterize the genetic and epigenetic changes that drive relapse in a mouse model of transplantation. In Projects 3 and 4, we will utilize enhanced WGS, error-corrected sequencing, bulk RNA-seq, scRNA-seq, and phased-read data to define the mechanisms that drive subclonal expansion and progression from MDS to sAML (Project 3), or the specific effects of TP53 mutations on the development of aneuploid AML (Project 4). Answering the questions outlined in these projects requires deep integrative analysis that goes far beyond the simple mutation counting that was a hallmark of previous genomic studies. This requires common infrastructure, comprehensive databases, and extensive expertise that will be provided by tight integration between project leadership and the scientists in Core C.

项目概要/摘要 Core C 的目标是提供 AML 基因组和表观基因组的高通量生产和分析 该 PPG 中所有四个项目的序列数据。这包括测序、体细胞和种系变异 检测和验证以及多种数据类型的集成。这将通过产生高质量的 DNA 和 RNA 测序数据并使用尖端算法和技术对其进行分析。 具体目标/核心服务1：（序列制作） Core C 中的样品测序将使用 Illumina HiSeqX、4000 和 NovaSeq 平台进行。 Core C 中生成的数据将是全面的：全基因组、外显子组和 DNA 捕获验证， 以及纠错测序、单细胞 RNA-seq、总 RNA 和小 RNA-seq、全基因组亚硫酸氢盐 测序和其他定制表观遗传分析。这些数据将通过最先进的技术进行处理 基因组管道产生主要结果，如序列比对和变体调用。 具体目标/核心服务2：（生物信息分析） 这些管道为详细的、新颖的和迭代的分析提供了一个起点，这些分析将在 核心 C 和 是每个项目的基础。项目 1 将需要对基因组和 表观基因组（转录组、scRNA-Seq、WGBS）数据，以更好地定义驱动启动的事件， 具有和不具有 DNMT3A 突变的样本中的进展和复发。在项目 2 中，我们将利用我们的 具有免疫基因组学经验来定义介导同种异体移植的次要组织相容性抗原 反应，并描述导致小鼠模型复发的遗传和表观遗传变化 移植。在项目 3 和 4 中，我们将利用增强型 WGS、纠错测序、bulk RNA-seq、 scRNA-seq 和分阶段读取数据来定义驱动亚克隆扩增和进展的机制 从 MDS 到 sAML（项目 3），或 TP53 突变对非整倍体 AML 发展的具体影响 （项目 4）。 回答这些项目中概述的问题需要深入的综合分析，这远远超出了 简单的突变计数是以前基因组研究的一个标志。这需要共同 紧密集成将提供基础设施、综合数据库和广泛的专业知识 项目领导和 Core C 科学家之间的关系。