Systems Biology of Early Atopy (SUNBEAM) Analysis and Bioinformatics Center

PROJECT SUMMARY Food allergy (FA) and atopic dermatitis (AD) are common chronic conditions of atopy affecting 10% and 20% of children, respectively. Individuals with FA are at daily risk for potentially life-threatening hives, angioedema, respiratory difficulty, cardiovascular compromise, gastrointestinal distress, and/or anaphylaxis following ingestion of a food antigen to which they are sensitized. Individuals with AD must live with chronically pruritic, inflamed skin that can cover a significant proportion of their bodies and become infected. The development of FA is frequently preceded by AD, suggesting shared risk factors and overlapping pathobiology. FA and AD are complex diseases, and parsing the biological heterogeneity hidden under their clinical umbrellas is paramount to improving their prevention, diagnosis, and clinical management. A systems biology approach where the biology of FA and AD are investigated comprehensively at several levels may help identify new knowledge about the development of allergy. Systems Biology of Early Atopy (SunBEAm) is a general population pre-birth cohort study initiated by the NIAID to study the role and inter-relationships of genetic, clinical, biological, and environmental early-life factors in the development of allergic diseases, with an emphasis on FA and AD. Pregnant women, children born to them, and the children's biological fathers are being enrolled and phenotyped with longitudinal biosample collections. A central goal of SunBEAm is to apply systems biology to identify mechanisms and biomarkers underlying the development of FA, AD, and their endotypes. The overarching goal of this SunBEAm Analysis & Bioinformatics Center (ABC) application is to create a center for assaying SunBEAm biosamples using omics, and to apply integrative systems biology to identify novel determinants of FA and AD. Our application centers on these five specific aims: (1) Assay biosamples from SunBEAm participants to generate longitudinal, multi-scale omic data that will inform on the development of FA and AD; (2) Analyze the systems-wide omic data generated to identify novel biomarkers, endotypes, and mechanisms underlying the development of FA and AD; (3) Integrate data across molecular dimensions to identify key drivers and predictors of FA and AD development; (4) Share all generated data, create a centralized platform for SunBEAm data and bioinformatic innovations, and build capacity for the integration of future SunBEAm omics data; and (5) Develop infrastructure for interactions with the SunBEAm Steering Group, the NIAID Statistical and Clinical Coordinating Center, and NIAID. With this award, we will create a center for unprecedented systems allergy research. In addition to an investigator team with world- class expertise in multi-omics, systems biology, computational biology, data science, and bioinformatics, our team also includes physician-scientists and immunologists who directly designed and continue to actively drive the ongoing enrollment and implementation of SunBEAm. Our team's experience, expertise, and proven track record will ensure the success of SunBEAm-ABC.