Allergic diseases (asthma, allergic dermatitis (AD), allergic rhinitis, food allergy and eosinophilic esophagitis (EoE)) commonly affect US children and have substantial lifetime co-morbidity. Our findings over the last 3 funding cycles identify and implicate novel epithelial pathways as key drivers of allergic inflammation and allergic disease pathogenesis. However, how these key drivers and other epithelial pathways contribute to development, persistence, progression and remission of allergic disease remains largely unknown. Our Center is focused on refining current atopic march paradigms and elucidating the epithelial-centric mechanisms that drive the atopic march. This proposal's overarching hypothesis is that homeostatic mechanisms at epithelial surfaces, upon dysregulation, promote allergic inflammation and contribute to the persistence, progression, remission, and resolution of allergic disease(s). This hypothesis will be tested by three integrated and synergistic projects that combine epidemiologic, basic, translational, and clinical research approaches. The Data Integration and Analysis Core's (DIAC) purpose is to provide the quantitative expertise to accomplish the overall objectives, curate and integrate data, and perform synergistic analyses. The DIAC's expertise in quantitative genetics, genomics, statistics, ancestry, and bioinformatics enhances the capacity for rigorous and reproducible research that will be applied to advance the goals of the overall Center as well as assist the project investigators with their specific hypotheses and aims. This DIAC's aims are to 1) curate, integrate, and share data and results across the U19 Center team and with the scientific community; 2) provide analytic rigor and expertise to the Center Projects so that the Center can achieve its overarching goal and the Projects can achieve their goals; and 3) perform synergistic analyses across all Projects so the Center can achieve its full potential. Our longstanding success in evaluating the role of the epithelium in allergic disorders coupled with our MPAACH longitudinal cohort, novel experimental systems to perform mechanistic studies, and analytic expertise, uniquely position us to accomplish the Center objectives. Successful completion of the proposed studies will provide novel insights into a key question in the allergy field: Why is allergic inflammation restricted to one tissue in some cases, while it progresses to involve additional tissues in other individuals?