Core C - Sequencing and Analysis.

项目总结/摘要 核心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。 本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，以及许多数据类型的集成。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进行分析。 具体目标/核心服务1：（序列制作） 将使用Illumina HiSeqX、4000和NovaSeq平台对核心C中的样品进行测序。 核心C产生的数据将是全面的：全基因组、外显子组和DNA的捕获验证， 以及纠错测序、单细胞RNA-seq、总RNA-seq和小RNA-seq、全基因组亚硫酸氢盐 测序和其他定制的表观遗传分析。这些数据将通过最先进的 基因组管道，以产生主要结果，如序列比对和变异调用。 具体目标/核心服务2：（生物信息学分析） 这些管道为详细的、新颖的和迭代的分析提供了一个起点， Core 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，以更好地定义驱动起始的事件， 在具有和不具有DNMT 3A突变的样品中的进展和复发。在项目2中，我们将利用 在免疫基因组学中确定介导同种异体移植的次要组织相容性抗原的经验 反应，并表征在小鼠模型中驱动复发的遗传和表观遗传变化。 移植在项目3和4中，我们将利用增强的WGS，纠错测序，批量RNA-seq， scRNA-seq和分阶段读取数据，以定义驱动亚克隆扩增和进展的机制 从MDS到sAML（项目3），或TP 53突变对非整倍体AML发展的特定影响 （项目4）。 要解决这些项目中提出的问题，需要进行深入的综合分析， 简单的突变计数是以前基因组研究的标志。这需要共同的 基础设施、全面的数据库和广泛的专业知识将通过紧密集成提供 项目领导和C区科学家之间的联系

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.