Bioinformatics Core

生物信息学核心

基本信息

批准号：
10745014
负责人：
John Damian Shaughnessy
金额：
$ 13.74万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-01 至 2027-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10745014
关键词：
Archives Arkansas Benign Bioinformatics Biology Biopsy Bone Marrow Bone marrow biopsy CST6 gene Candidate Disease Gene Cells Characteristics Clinical Clinical Research Clinical Trials Data Database Management Systems Databases Development Diagnosis Disease Enrollment Ensure Gene Expression Profiling Genes Genomics Grant Image Immune system Laboratories Lesion Longterm Follow-up Malignant - descriptor Malignant Neoplasms Medical Methods Molecular Monoclonal Gammapathies Monoclonal gammopathy of uncertain significance Multiple Myeloma Natural History Outcome PET/CT scan Pathway interactions Patients Phase Plasma Cell Neoplasm Plasma Cells Premalignant Cell Premalignant Change Publishing Recording of previous events Research Research Project Grants Resources Retrieval Risk Role Sampling Science Serial Magnetic Resonance Imaging System Techniques Testing Therapeutic Intervention Time Tissue-Specific Gene Expression Tissues Universities Update Waldenstrom Macroglobulinemia Work archive data arm base bench to bedside bench-to-bedside translation bone bone cell cancer prevention clinical investigation data archive data infrastructure data management data sharing experimental study genetic analysis informatics infrastructure innovation neoplastic cell patient population prognostic repository single-cell RNA sequencing translational research program tumor heterogeneity user-friendly virtual

项目摘要

Bioinformatics Core Project Summary All forms of the incurable plasma cell malignancies, multiple myeloma (MM), and Waldenstrom’s macroglobulinemia (WM) emerge from a precursor condition known as monoclonal gammopathy of undermined significance (MGUS). Genetic analyses of MGUS cells have provided evidence that it is a genetically advanced lesion virtually indistinguishable from MM. The risk of conversion of MGUS to MM is approximately 1% per year. The mechanisms underlying the MGUS to MM or WM transformation are unclear. One possibility is that precancerous cells alter the bone marrow microenvironment and/or immune system to facilitate the conversion to overt malignancy. The Bioinformatics Core will provide in-depth genomic analysis of tissues from a spectrum of plasma cell dyscrasias, including invaluable serial samples of purified tumor cells and whole bone-marrow biopsies from patients with MGUS enrolled in observational clinical trials and followed over the past 20 years. The core will also analyze experimental samples obtained from Research Projects 1 and 2 of the Cancer Prevention-Interception Against MGUS Progression (CAP-MGUS Center) that aim to understand and treat premalignant changes in the plasma cells, immune system, and microenvironment in order to eliminate and/or delay the onset of malignant transformation. The Myeloma Center at the University of Arkansas for Medical Sciences (UAMS), where the core will be housed, is a unique resource for laboratory and clinical investigation of plasma cell dyscrasias with a long history of studying the biology of these diseases. The Bioinformatics Core will use innovative bioinformatics techniques in the context of a large clinically and molecularly annotated archive of primary plasma cell dyscrasias, to identify molecular correlates associated with the conversion of the benign asymptomatic MGUS to MM or WM. These discoveries will form the basis for hypotheses that will be tested in the CAP-MGUS Center projects, from which additional molecular data from experimental systems will be analyzed in the Bioinformatics Core.

生物信息学核心项目概要所有形式的无法治愈的浆细胞恶性肿瘤、多发性骨髓瘤 (MM) 和瓦尔登斯特伦氏病巨球蛋白血症 (WM) 是由一种被称为单克隆伽马病的先兆病症引起的 MGUS 细胞的遗传分析提供了证据，表明它是一种遗传先进的细胞。病变与 MM 几乎无法区分，每年 MGUS 转化为 MM 的风险约为 1%。 MGUS 向 MM 或 WM 转化的机制尚不清楚，一种可能性是。癌前细胞改变骨髓微环境和/或免疫系统以促进转化生物信息学核心将为一系列组织提供深入的基因组分析。浆细胞恶液质，包括纯化肿瘤细胞和全骨髓的宝贵系列样本 MGUS 患者的活检样本参加了观察性临床试验，并在过去 20 年进行了随访。该核心还将分析从癌症研究项目 1 和 2 获得的实验样本预防-拦截 MGUS 进展（CAP-MGUS 中心）旨在了解和治疗浆细胞、免疫系统和微环境的癌前变化，以消除和/或延缓恶性转化的发生阿肯色大学医学院的骨髓瘤中心。核心所在的科学 (UAMS) 是实验室和临床研究的独特资源浆细胞恶液质的研究具有悠久的生物信息学核心历史。将在大型临床和分子注释档案的背景下使用创新的生物信息学技术原发性浆细胞恶液质，以确定与良性浆细胞转化相关的分子相关性无症状 MGUS 至 MM 或 WM 的这些发现将构成将在 2017 年进行检验的假设的基础。 CAP-MGUS 中心项目，来自实验系统的额外分子数据将来自该项目在生物信息学核心中进行分析。