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.