Core B: Integrative Genomics Core

核心 B：综合基因组学核心

• 批准号: 10456242
• 负责人: Soumya Raychaudhuri
• 金额: $ 24.5万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-15 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10456242
• 关键词: ATAC-seq; Algorithms; Allergic Disease; Archives; Asthma; Automobile Driving; Basal Cell; Bioinformatics; Biological Response Modifier Therapy; Cell Aging; Cell Differentiation process; Cells; Cellular biology; Chromatin; Clinical Trials; Computational Biology; Computing Methodologies; Data; Data Analytics; Data Science; Data Set; Development; Discriminant Analysis; Disease; Epithelial; Event; Gene Expression; Genetic Transcription; Genomic approach; Genomics; Goals; Grant; Heterogeneity; High Performance Computing; Hospitals; Human Resources; Immune; Individual; Institutes; Interleukin-13; Interleukin-4; Mediating; Medical; Methods; Modeling; Molecular; Morphologic artifacts; Nasal Polyps; National Institute of Allergy and Infectious Disease; National Institute of Arthritis and Musculoskeletal and Skin Diseases; Nose; Occupations; Pathway interactions; Patients; Pharmaceutical Preparations; Population; Positioning Attribute; Procedures; Process; Proteomics; RNA; Reproducibility; Research; Research Personnel; Research Project Grants; Rheumatoid Arthritis; Running; Sampling; Series; Statistical Data Interpretation; Statistical Methods; Systemic Lupus Erythematosus; Systems Biology; Technology; Testing; Therapeutic; Tissue-Specific Gene Expression; Tuberculosis; Woman; Work; analytical tool; aspirin-exacerbated respiratory disease; base; cell type; chromatin protein; chromatin remodeling; chronic rhinosinusitis; data integration; epigenome; epigenomics; experience; experimental study; firewall; functional genomics; immunopathology; informatics infrastructure; insight; large datasets; large scale data; mast cell; medical schools; multiple omics; polyposis; programs; response; single-cell RNA sequencing; stem cells; success; synergism; targeted treatment; terabyte; transcriptome; transcriptome sequencing; transcriptomics

Core B: Integrative Genomics Core ABSTRACT This U19 re-competing proposal entitled “Pathophysiologic and Therapeutic Mechanisms of Aspirin Exacerbated Respiratory Disease” seeks to understand the mechanisms of chronic rhinosinusitis with nasal polyposis (CRSwNP) and aspirin exacerbated respiratory disease (AERD) at a multi-omic molecular and cellular level. The Integrative Genomics Core (IGC) will utilize cutting-edge technologies and computational methods, many of which were developed by our group, to support the objectives of the three Projects, each of which is focused on a different aspect of Type II immunopathology (T2I). The IGC will be based at the Raychaudhuri lab at the Brigham and Women’s Hospital (BWH), where the BWH Single Cell Genomics Core is also based. The IGC is composed of researchers with 10+ years of experience leading large-scale functional genomics projects, processing large datasets, and performing statistical analyses to integrate different layers of multi-dimensional information for the understanding of immune-mediated diseases. The IGC has a robust informatics infrastructure where terabytes of data can be stored and high-performance computing jobs can be run. Specifically, the IGC will (i) generate the single-cell and bulk datasets profiling RNA, open chromatin and protein levels for all three Projects, (ii) process and perform the quality check of each dataset, (iii) apply normalization and batch correction procedures, (iv) perform reproducible bioinformatic and statistical analyses, and (v) archive all experimental data and results on a firewall and password protected internal network. The IGC will perform analyses according to each Project’s needs to gain insights into mast cell heterogeneity and differentiation (Project 1), basal cell differentiation and senescence programs (Project 2), and the molecular underpinnings of drug response in a clinical trial (Project 3). Additionally, the IGC will facilitate synergy and data integration across all three Projects, contributing to new mechanistic insights into the control and therapy of T2I in CRSwNP and AERD.

核心 B：综合基因组学核心 抽象的 本U19复赛提案题为“阿司匹林加剧的病理生理学和治疗机制” 《呼吸系统疾病》旨在了解慢性鼻窦炎伴鼻息肉病的机制 （CRSwNP）和阿司匹林在多组学分子和细胞水平上加剧了呼吸道疾病（AERD）。 综合基因组学核心（IGC）将利用尖端技术和计算方法，其中许多 由我们小组开发，以支持三个项目的目标，每个项目都侧重于 IGC 将设在位于该中心的 Raychaudhuri 实验室。 Brigham 妇女医院 (BWH)，也是 BWH 单细胞基因组学核心的所在地。 由具有 10 多年领导大规模功能基因组学项目经验的研究人员组成， 处理大型数据集，并执行统计分析以整合多维的不同层 用于了解免疫介导疾病的信息 IGC 拥有强大的信息学基础设施。 其中可以存储数 TB 的数据并可以运行高性能计算作业，具体来说，就是 IGC。 将 (i) 生成单细胞和批量数据集，分析所有三个的 RNA、开放染色质和蛋白质水平 项目，(ii) 处理并执行每个数据集的质量检查，(iii) 应用归一化和批量校正 程序，(iv) 执行可重复的生物信息学和统计分析，以及 (v) 存档所有实验数据 IGC 将根据防火墙和密码保护的内部网络进行分析。 每个项目需要深入了解肥大细胞异质性和分化（项目 1）、基底细胞 分化和衰老程序（项目 2），以及药物反应的分子基础 此外，IGC 将促进所有三个项目的协同和数据整合， 为 CRSwNP 和 AERD 中 T2I 的控制和治疗提供新的机制见解。