Network and Systems Biology Scientific Core 3

SC3项目总结 心房颤动(房颤)是最常见的心律失常，也是心血管死亡和死亡的主要危险因素 卒中。由于肥胖和人口年龄的增加，房颤的发病率进一步增加，这与 与房颤的风险和进展有关。尽管房颤的诊断和管理取得了重大进展，但治疗 临床结果仍然很差，距离上一次发现房颤药物已经过去了十多年。这个 此PPG应用程序的总体目标是使用基因组和转录组发现来识别预防性和 房颤的治疗策略并向临床应用发展。我们的中心假设是 增加我们对涉及遗传、转录、代谢和 心房的结构变化将使我们能够准确定位可能的靶点，以实现更安全和更有效的治疗 战略。为了帮助项目朝着这些目标前进，网络和系统生物学核心(SC3) 将负责所有RNA测序数据的处理、分析、整合和网络建模， 包括大量和单核、蛋白质组学、代谢组学和功能分析数据 四个项目。所有项目都建议广泛使用RNA测序研究，使SC3成为完整的 为他们的成功干杯。功能分析数据将主要在SC1和SC2的指导下生成 项目，然后发送到SC3进行分析并与RNAseq集成。SC3将与该项目密切合作 帮助解释和可视化结果的领导和人员，包括来自传统差异的结果 分析以及更先进的网络和系统生物学方法。SC3有一种独特的混合 专业知识和经验，将具有RNA处理和建模技能的人员以及具有 网络和系统生物学的重点，以及严格和可重复的管道实施 将有助于使PPG中的四个项目填补知识空白，并在理解方面取得进展 和治疗房颤。SC3将向PPG提供两组主要服务，这些服务围绕 正在分析的数据类型。AIM 1将专注于RNA测序数据服务，包括高级 网络和系统生物学方法，而Aim 2也将专注于功能分析数据的服务 作为与RNA数据的整合。

SC3 PROJECT SUMMARY Atrial fibrillation (AF) is the most common arrhythmia and a major risk factor for cardiovascular mortality and stroke. Incidence of AF is further increasing due to the rise in obesity and age of the population, factors closely related to AF risk and progression. Despite significant advances in AF diagnosis and management, treatment and clinical outcomes remain poor and more than a decade has passed since the last AF drug discovery. The overall goal of this PPG application is to use genomic and transcriptomic findings to identify preventative and therapeutic strategies for AF and develop them towards clinical application. Our central hypothesis is that increasing our knowledge about molecular mechanisms involved in genetic, transcriptomic, metabolic and structural changes in the atria will allow us to pinpoint possible targets for safer and more effective therapeutic strategies. To help the projects advance towards these goals, the Network and Systems Biology Core (SC3) will be responsible for the processing, analysis, integration and network modeling of all RNA sequencing data, including bulk and single nuclei, proteomic, metabolomics, and functional assay data used and generated in the four projects. All Projects have proposed extensive use of RNA sequencing studies, making SC3 integral to their success. Functional assay data will be generated primarily in SC1 and SC2 under direction of the Projects and then sent to SC3 for analysis and integration with RNASeq. SC3 will work closely with the project leads and personnel to help interpret and visualize the results including those from traditional differential analyses as well as from more advanced network and systems biology approaches. SC3 has a unique blend of expertise and experience, combining personnel with RNA processing and modeling skills and those with a network and systems biology focus, which together with a rigorous and reproducible pipeline implementation will help enable the four projects in this PPG to fill knowledge gaps and make advances towards understanding and treating atrial fibrillation. SC3 will provide two major groups of services to the PPG organized around the type of data being analyzed. Aim 1 will focus on services for RNA sequencing data, including advanced network and systems biology approaches, while Aim 2 will focus on services for functional assay data as well as integrations with the RNA data.