Network and Systems Biology Scientific Core 3

网络与系统生物学科学核心 3

• 批准号: 10646354
• 负责人: John Barnard
• 金额: $ 23.79万
• 依托单位: CLEVELAND CLINIC LERNER COM-CWRU
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10646354
• 关键词: Age; Arrhythmia; Atrial Fibrillation; Biological Assay; Cell Nucleus; Clinical; Data; Detection; Diagnosis; Disease; Doctor of Philosophy; Gene Expression; Genes; Genetic; Genomics; Goals; Heart Atrium; Human Resources; Incidence; Kinetics; Knowledge; Lead; Metabolic; Modeling; Molecular; Obesity; Outcome; Population; Process; Proteins; Proteomics; RNA; RNA Processing; Reproducibility; Research Institute; Research Personnel; Risk; Sample Size; Sampling; Services; Stroke; Study models; Systems Biology; Therapeutic; Visualization; Work; cardiovascular risk factor; cell type; clinical application; differential expression; drug discovery; experience; flexibility; genome wide association study; metabolomics; mortality; network models; power analysis; single nucleus RNA-sequencing; skills; success; therapeutically effective; trait; transcriptome sequencing; transcriptomics

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.

SC3项目摘要 心房颤动（AF）是最常见的心律失常，也是心血管死亡率的主要危险因素 中风。由于肥胖和人口年龄的增长，AF的发病率进一步增加 与AF风险和进展有关。尽管在AF诊断和管理方面取得了重大进展，但 自上次AF药物发现以来，临床结果仍然很差，并且已经过去了十多年。这 该PPG应用的总体目标是使用基因组和转录组发现来识别预防性和 AF的治疗策略并将其开发为临床应用。我们的中心假设是 提高我们对参与遗传，转录组，代谢和 心房的结构变化将使我们能够指出可能更安全，更有效治疗的可能目标 策略。为了帮助项目迈向这些目标，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，集成和网络建模， 包括散装和单核，蛋白质组学，代谢组学以及使用和生成的功能分析数据 四个项目。所有项目都提出了RNA测序研究的广泛使用，使SC3积分不可或缺 取得成功。功能测定数据将主要在SC1和SC2中生成 项目，然后发送到SC3进行分析和与RNASEQ集成。 SC3将与该项目紧密合作 潜在客户和人员来解释和可视化结果，包括传统差异的结果 分析以及更高级的网络和系统生物学方法。 SC3具有独特的混合 专业知识和经验，将人员与RNA处理和建模技巧相结合，以及与 网络和系统生物学重点，以及严格且可重复的管道实施 将有助于使本PPG中的四个项目填补知识空白，并提高理解 并处理心房颤动。 SC3将向PPG提供两个主要的服务，并在PPG周围组织 分析数据类型。 AIM 1将专注于RNA测序数据的服务，包括高级 网络和系统生物学方法，而目标2也将专注于功能分析数据的服务 作为与RNA数据的集成。