Core B: Integrative Genomics Core

核心B：整合基因组学核心 摘要 这个U19重新竞争的提案题为“阿司匹林加重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鼻息肉病的机制 （CRSwNP）和阿司匹林在多组分子和细胞水平上加重呼吸系统疾病（AERD）。的 整合基因组学核心（IGC）将利用尖端技术和计算方法，其中许多 这是由我们的团队开发的，以支持三个项目的目标，每个项目都集中在 II型免疫病理学（T2I）的另一个方面。IGC将设在Raychaudhuri实验室， 布里格姆妇女医院（BWH），BWH单细胞基因组学核心也位于那里。IGC是 由拥有10年以上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，以整合多维数据集的不同层， 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TB级的数据，并可以运行高性能计算作业。具体而言，IGC 将（i）生成所有三种RNA、开放染色质和蛋白质水平的单细胞和批量数据集 项目，（ii）处理和执行每个数据集的质量检查，（iii）应用标准化和批量校正 程序，（iv）进行可重现的生物信息学和统计分析，以及（v）存档所有实验数据 并在防火墙和密码保护的内部网络上产生。IGC将根据以下内容进行分析： 每个项目都需要深入了解肥大细胞的异质性和分化（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， 临床试验（项目3）。此外，IGC将促进所有三个项目的协同作用和数据整合， 有助于对CRSwNP和AERD中T2I的控制和治疗的新的机制见解。

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.