Core C: Immune bioinformatics and biostatistics

核心C：免疫生物信息学和生物统计学

• 批准号: 10360422
• 负责人: Katherine L. Nathanson
• 金额: $ 28.81万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10360422
• 关键词: Bioinformatics; Biological Assay; Biometry; Biostatistics Core; Biostatistics Shared Resource; Chromatin; Clinical; Clinical Data; Clinical Research; Clinical Trials; Consult; DNA; DNA analysis; Data; Data Analyses; Databases; Generations; Genetic; Goals; Graph; Human; Immune; Immunologics; Immunotherapy; Infrastructure; Knowledge; Libraries; Link; Machine Learning; Malignant Neoplasms; Manuscripts; Massive Parallel Sequencing; Mus; Patients; Performance; Play; Preparation; Productivity; Progress Reports; RNA; Radiation; Radiation therapy; Recording of previous events; Relapse; Research; Research Design; Research Personnel; Research Project Grants; Resistance; Resource Sharing; Resources; Role; Safety; Sample Size; Sampling; Schools; Services; T-Cell Receptor; T-Lymphocyte; Techniques; Transposase; Tumor-Infiltrating Lymphocytes; Universities; Work; base; biomarker evaluation; clinical biomarkers; clinical trial analysis; data integration; data sharing; database design; design; exome; exosome; experience; feature selection; genomic data; immune checkpoint blockade; insight; knowledge base; medical schools; member; multiple data types; neoantigens; pre-clinical; preclinical study; relational database; response; tumor

SUMMARY The Immune Bioinformatics and Biostatistics (Core C) will provide critical infrastructure and shared resources of biostatistic and bioinformatic expertise for the design, conduct and analyses of the Research Projects within the P01 - “Radiation and Checkpoint Blockade for Cancer Immune Therapy.” Core C will provide services to P01 projects at every stage of research. Core members will: 1) consult with investigators on selection of study designs; 2) develop a relational database to store clinical trial patient correlative data for analysis; 3) generate DNA and RNA-based massively parallel sequencing data from tumors, exosomes, PMBCs (T cells), and tumor infiltrating lymphocytes; 4) conduct efficient and robust data analyses, utilizing both bioinformatics and biostatistics; 5) perform higher level secondary and integrative analyses using multiple pre-clinical and clinical data types; 6) create graphs and tables, assist investigators with the preparation of progress reports, presentations and manuscripts; 7) consult on the design of subsequent research; and 8) be responsible for the implementation of the Shared Resources Plan in regards to Genomic Data Sharing. These goals will be implemented through the following specific aims – Aim 1) To provide biostatistical expertise in design and analysis for the proposed projects; Aim 2) To provide support for the generation and initial analysis of DNA- and RNA-based massively parallel sequencing data; and Aim 3) To perform secondary and integrative analyses across platforms and data types. A major theme of the P01 is studying the effect of checkpoint blockade and radiation therapy in humans through clinical trials, and concurrently performing linked pre-clinical studies in mice. Core C members will play a vital role in facilitating the comparison between the two groups, as they will be involved in the same analyses on human and mouse samples providing a conduit of knowledge between Projects. Core members have extensive experience in clinical trials biostatistics, database design and implementation, performance of massively parallel sequencing, bioinformatics analysis, and the utilization of analytical techniques for integration of the multiple data types generated from the Projects. The Immune Bioinformatics and Biostatistics Core will serve as an essential resource for the P01, providing specialized expertise to allow investigators to complete their research in a robust and efficient fashion. Members of Core C will work in a synergistic and cooperative fashion with Project investigators to determine the safety, efficacy and mechanism of the combination of local radiation therapy and immune checkpoint blockade and to understand the immunologic and genetic features of pre-clinical and clinical samples that are determinants of response, resistance, and relapse.

概括 免疫生物信息学和生物统计学（核心 C）将提供关键基础设施和共享资源 用于设计、实施和分析研究项目的生物统计和生物信息专业知识 P01 - “癌症免疫治疗的放射和检查点封锁”核心 C 将提供服务 P01项目在每个研究阶段的核心成员将：1）与研究者就研究选择进行协商。 设计；2）开发关系数据库来存储临床试验患者相关数据以供分析；3）生成 来自肿瘤、外泌体、PMBC（T 细胞）和肿瘤的基于 DNA 和 RNA 的大规模并行测序数据 浸润淋巴细胞；4）利用生物信息学和 5) 使用多种临床前和临床数据进行更高水平的二次和综合分析 数据类型；6）创建图表，协助调查人员准备进度报告， 7）对后续研究的设计进行咨询；8）负责 实施有关基因组数据共享的共享资源计划将是这些目标。 通过以下具体目标来实施 – 目标 1) 提供设计和实施方面的生物统计专业知识 分析拟议项目；目标 2) 为 DNA 的生成和初步分析提供支持 目标 3) 进行二次综合训练 P01 的一个主要主题是研究检查点的影响。 通过临床试验对人体进行封锁和放射治疗，并同时进行相关的临床前研究 核心 C 成员的小鼠研究将在促进两组之间的比较方面发挥至关重要的作用，因为 他们将参与对人类和小鼠样本的相同分析，提供知识渠道 核心成员在临床试验生物统计学、数据库设计方面拥有丰富的经验。 大规模并行测序的实现、性能、生物信息学分析和利用 用于集成免疫项目生成的多种数据类型的分析技术。 生物信息学和生物统计学核心将作为 P01 的重要资源，提供专业的 专业知识使研究人员能够以稳健和高效的方式完成他们的研究。 C 将与项目研究人员以协同和合作的方式工作，以确定安全性、有效性 局部放射治疗与免疫检查点阻断相结合的机制及机制 了解临床前和临床样本的免疫学和遗传特征，这些特征是决定因素 反应、抵抗和复发。