CPML - Core C: Bioinformatics & Biostatistical Core

CPML - 核心 C：生物信息学

• 批准号: 8933501
• 负责人: Jinghui Zhang
• 金额: $ 61.2万
• 依托单位: ST. JUDE CHILDREN'S RESEARCH HOSPITAL
• 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/8933501
• 关键词: Acute Lymphocytic Leukemia; Address; Adult; Adult Acute Lymphocytic Leukemia; Adverse effects; Age; Algorithms; Bioinformatics; Biological Assay; Biological Process; Biostatistics Core; Characteristics; Child; Childhood; Childhood Acute Lymphocytic Leukemia; Classification; Clinical; Clinical Data; Clinical Trials; Clinical Trials Design; Coupled; CpG Islands; DNA; DNA Methylation; Data; Data Analyses; Data Quality; Deposition; Detection; Ensure; Epigenetic Process; Future; Genes; Genetic; Genetic Markers; Genome; Genomics; Goals; Individual; Inherited; International; Joints; Knowledge; Laboratories; Methylation; Molecular Profiling; Patients; Pharmaceutical Preparations; Pharmacogenomics; Phenotype; Positioning Attribute; Protein Isoforms; Publications; RNA; RNA Sequences; Regimen; Reproducibility; Research; Research Design; Research Infrastructure; Research Personnel; Research Project Grants; Resources; Scientist; Standardization; Statistical Data Interpretation; TNFRSF5 gene; Toxic effect; Transcript; Translating; Treatment Protocols; Treatment outcome; Variant; Work; analytical method; arm; base; clinical infrastructure; data management; data sharing; design; epigenetic marker; epigenomics; exome; exome sequencing; experience; genome wide methylation; genomic variation; improved; in vivo; leukemia; model building; next generation sequencing; non-genomic; novel strategies; pre-clinical; precision medicine; response; sound; tool; transcriptome sequencing; transcriptomics; treatment response; tumor

ABSTRACT – CORE C The three research projects outlined in this P50 Center proposal use multi-dimensional genomic and epigenomic assays, based on next-generation sequencing and microarray approaches (implemented in Core B), to gain understanding of the inherited variations and somatically acquired genetic and epigenetic alterations that drive treatment response of pediatric and adult acute lymphoblastic leukemia (ALL). The Bioinformatics/Biostatistics Core (Core C) provides biostatistical and bioinformatic support to ensure each project generates high quality data with analytical accuracy and reproducibility. Core C includes designated scientists to analyze genomic and epigenetic data for each project; to provide uniform and high quality approaches to variant calling, annotation, and functional assessments for germline and somatic tumor variations; and to perform statistical analyses. Working closely with Cores A and B, they develop and provide critical infrastructure necessary for data management and facilitate cross-project and public data sharing. Together with the project Leaders and Investigators, using statistically sound analyses, Core C will identify important biological processes involved in the classification and treatment response of ALL and determine the genetic and epigenetic markers that are associated with discrete phenotypes defined in the Projects: in vivo response (Project 1), drug sensitivitity (Project 2), and adverse effects (Project 3). Core C will integrate cross- platform genomic, transcriptomic, and epigenomic data. Core C also provides critical input on study design and power estimates for both clinical and preclinical aims of the Projects. In Aim 3, Core C will coordinate addressing the Center's overarching goal of using genome variations identified in the Projects to integrate clinical and genomic data for designing precision medicine approaches that can be used to improve treatment outcomes for children and adults with ALL.

抽象-核心C P50中心提案中概述的三个研究项目使用了多维基因组和 基于下一代测序和微阵列方法的表观基因组分析(在CORE实施 B)了解遗传变异和躯体获得性遗传和表观遗传改变 推动儿童和成人急性淋巴细胞白血病(ALL)的治疗反应。这个 生物信息学/生物统计核心(核心C)提供生物统计和生物信息支持，以确保每个 Project生成具有分析准确性和重复性的高质量数据。核心C包括指定的 科学家为每个项目分析基因组和表观遗传学数据；提供统一和高质量的数据 生殖系和体细胞肿瘤的变异叫声、注释和功能评估方法 变化；并进行统计分析。他们与核心A和B密切合作，开发并提供 数据管理所需的关键基础设施，并促进跨项目和公共数据共享。 与项目负责人和调查人员一起，使用可靠的统计分析，Core C将确定 重要的生物学过程涉及ALL的分类和治疗反应，并决定 与项目中定义的离散表型相关的遗传和表观遗传标记：体内 反应(项目1)、药物敏感性(项目2)和不良反应(项目3)。核心C将整合交叉- 平台基因组、转录和表观基因组数据。核心C还提供了研究设计和研究的关键投入 对项目的临床和临床前目标的功率估计。在目标3中，核心C将协调 解决该中心的首要目标，即利用项目中确定的基因组变异来整合 临床和基因组数据用于设计可用于改善治疗的精确医学方法 儿童和成人急性淋巴细胞白血病的结果。