Core D: Biomarkers and Bioinformatics

核心 D：生物标志物和生物信息学

• 批准号: 9884566
• 负责人: Raajit Rampal
• 金额: $ 58.4万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 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/9884566
• 关键词: Bioinformatics; Biological; Biological Assay; Biological Markers; Biology; Clinical; Clinical Research; Clinical Trials; Clonal Hematopoietic Stem Cell; Correlative Study; Cytogenetics; Cytokine Gene; DNA Sequence Alteration; Data; Dependence; Disease; Gene Expression; Gene Expression Profiling; Genetic; Genomics; Goals; Histopathology; Myelofibrosis; Myeloproliferative disease; Pathogenesis; Pathway interactions; Patients; Reaction Time; Reproducibility; Research; Sampling; Serum; Somatic Mutation; Specimen; Therapeutic; Therapeutic Agents; Therapeutic Intervention; Therapeutic Trials; Tissue Banks; Tissues; Treatment Efficacy; Work; base; cytokine; data integrity; epigenomics; genomic profiles; innovation; insight; new therapeutic target; novel marker; novel therapeutics; preclinical study; prospective; repository; resistance mechanism; responders and non-responders; software infrastructure; stem; targeted treatment; tool; treatment responders

Abstract The overall aim of Core D is to provide correlative biomarker analyses of primary specimens in the MPN-RC tissue bank as well as from samples arising from all MPN-RC clinical trials and prospective tissue banking efforts. Core D will carry out assessment of somatic genomic alterations on all MPN-RC samples derived from tissue banking efforts, and from therapeutic trials at baseline and the time of response assessment. The core will also carry out dynamic analyses of other mechanism-based biomarkers (such as serum cytokines, gene expression profiling, cytogenetics, and histopathology) which pertain to each of the biologic and clinical studies in Projects 1-4. The use of genomic profiling will provide Projects 1-3 with the ability to select genetically annotated samples for biologic studies aimed at investigating the relationship between somatic mutations, biological features of disease pathogenesis, and therapeutic dependencies. The goal of these assays is to provide comprehensive genetic and biologic correlative studies as well as to help determine the mechanistic impact of the hypothesis-driven therapeutic interventions of clinical trials in Project 4. The core will also perform and analyze assays for Project 1-3, which are common to these projects. The proposed analyses will result in integrated genomic, gene expression, and cytokine data of a large number of clinically annotated and homogenously treated patients. As well, the clinical trials proposed in Project 4 are mechanistically based, and stem from work in Projects 1-3. The correlative biomarker assays are directly related to the proposed mechanisms of action of the therapeutic agents delineated and which will be investigated in Project 4. These studies will allow for an assessment of the mechanistic impact of specific therapeutic interventions and allow us to credential novel therapeutic targets and pathways. As well, these studies will allow biological assessment of treatment responders and non-responders, thus giving insight into mechanisms of resistance. Importantly, we have developed rigorous organizational tools in order to maintain data integrity, traceability and reproducibility standards when dealing with the amount and the variety of data involved in the large-scale biomarker analyses for this core. The integration of state-of-the-art and novel biomarker assays offered by Core D, with robust preclinical and clinical studies will afford a unique opportunity to gain new genomic, epigenomic and biologic insights into MPN pathogenesis.

抽象的 Core D 的总体目标是提供 MPN-RC 中主要样本的相关生物标志物分析 组织库以及来自所有 MPN-RC 临床试验和前瞻性组织库的样本 努力。 Core D 将对来自以下来源的所有 MPN-RC 样本进行体细胞基因组改变评估： 组织库工作，以及基线治疗试验和反应评估时间。核心 还将对其他基于机制的生物标志物（如血清细胞因子、基因 表达谱、细胞遗传学和组织病理学），与每项生物学和临床研究相关 在项目 1-4 中。基因组分析的使用将为项目 1-3 提供基因选择的能力 用于生物学研究的注释样本，旨在研究体细胞突变之间的关系， 疾病发病机制的生物学特征和治疗依赖性。这些测定的目的是 提供全面的遗传和生物学相关研究，并帮助确定机制 项目 4 中临床试验的假设驱动治疗干预的影响。核心还将执行 并分析项目 1-3 的测定，这些测定对于这些项目来说是常见的。拟议的分析将导致 整合了大量临床注释和数据的基因组、基因表达和细胞因子数据 均质治疗的患者。同样，项目 4 中提出的临床试验是基于机械原理的，并且 源于项目 1-3 的工作。相关生物标志物测定与提议的直接相关 所描述的治疗药物的作用机制将在项目 4 中进行研究。这些 研究将允许评估特定治疗干预措施的机械影响，并允许 我们可以证明新的治疗靶点和途径。此外，这些研究将允许生物学评估 治疗有反应者和无反应者，从而深入了解耐药机制。重要的是， 我们开发了严格的组织工具，以保持数据完整性、可追溯性和 处理大规模数据涉及的数量和种类时的再现性标准 该核心的生物标志物分析。集成了最先进的和新颖的生物标志物检测 核心 D 拥有强大的临床前和临床研究，将为获得新的基因组、 MPN 发病机制的表观基因组学和生物学见解。