PROJECT SUMMARY DATA SCIENCE CORE The Jackson Laboratory-Icahn School of Medicine at Mt. Sinai Cooperative Center on Human Immunology (JAX- ISMMS CCHI) aims to study lung tissue-resident immunity and its decline in older individuals. To manage and analyze the large volumes of multimodal data generated across the different Projects and the Sample Core, a dedicated Data Science Core (DSC) will be established with three Specific Aims. First, we will capture, integrate, and disseminate JAX-ISMMS CCHI data (Aim 1). To this end, we will establish a central data repository following FAIR principles and coordinate with U19 investigators to ensure data interoperability and reusability. Data will be shared in compliance with NIH policies and our Data Management and Sharing Plan. Web applications will be developed for data access and visualization, and figure generation for presentations and publications. Critical for meeting the goal of the JAX-ISMMS through supporting hypothesis-driven Projects 1 and 2, we will identify multimodal molecular signatures and phenotypes associated with impaired airway epithelium response to viral infection as a function of age (Aim 2). We will develop and employ fixed module repertoires and perform integrative data analyses to identify age-related immune pathways in response to viral infection. Finally, we will collectively interpret signatures associated with age-related alteration in airway immune responsiveness and select candidates for downstream validation experiments (Aim 3). Workshops will be organized to facilitate collaborative interpretation of datasets generated by our U19 Center and to select candidates for targeted profiling and functional validation experiments. Dr. Damien Chaussabel, Principal Computational Scientist at JAX, will lead the DSC, supported by a team of Computational Scientists, a Bioinformatics Analyst, and a Data Wrangler. The DSC will work with the other Cores, research Projects, and the Technology Development Project to mine harmonized data across the eight JAX-ISMMS U19 geographical sites. In sum, the DSC's activities are crucial for achieving the U19's objective of identifying age-related epithelial cell pathways driving immune dysfunction in the lung.