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.

项目摘要/摘要 Core C的目的是提供AML基因组和表观基因组的高通量产生和分析 该PPG中所有四个项目的序列数据。这包括测序，体细胞和种系变体 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来实现 DNA和RNA测序数据并使用尖端算法和技术对其进行分析。 特定的目标/核心服务1 ：（序列生产） Core C中样品的测序将使用Illumina Hiseqx，4000和Novaseq平台进行。 Core C中产生的数据将是全面的：整个基因组，外显子组和DNA的捕获验证， 以及错误校正的测序，单细胞RNA-seq，总和小的RNA-seq，整个基因组Bisulfite 测序和其他自定义表观遗传分析。这些数据将通过最新的 基因组管道产生主要结果，例如序列比对和变体调用。 特定的目标/核心服务2 ：（生物信息学分析） 这些管道为将发生的详细，新颖和迭代分析提供了一个起点 核心C，是每个项目的基础。项目1将需要基因组和基因组的综合分析 表观基因组学（转录组，SCRNA-SEQ，WGB）数据，以更好地定义驱动启动的事件， 进展，并在有和没有DNMT3A突变的样品中复发。在项目2中，我们将利用我们的 具有免疫基因组学的经验来定义介导异晶植物的较小组织相容性抗原 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WG，错误校正的测序，大量RNA-Seq， scrna-seq和阶梯式阅读数据，以定义驱动亚克隆扩展和进展的机制 从MDS到SAML（项目3），或TP53突变对非整倍体AML发展的特定影响 （项目4）。 回答这些项目中概述的问题需要深入的整合分析，这远远超出了 简单的突变计数是先前基因组研究的标志。这需要共同 基础架构，全面数据库和广泛的专业知识将通过紧密整合提供 在项目领导力与核心C的科学家之间。