Core 3: Integrative Models of Aging Core

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PROJECT SUMMARY – Integrative Models of Aging Core Aging is a multi-faceted, multi-scale and heterogeneous process. While specific pathways and genes associated with aging are beginning to emerge from computational modeling studies, in the age of high- throughput and single-cell sequencing, proteomic, and imaging analyses, researchers in the aging field must overcome a number of challenges to integrate and interpret these disparate and often massive datasets. Because of this high barrier to entry, biology of aging researchers are only beginning to approach the study of aging using integrated data-driven approaches. To support the mission of the San Diego Nathan Shock Center of Excellence in the Basic Biology of Aging (SD-NSC), the Integrative Models of Aging Core (Modeling Core) will address these challenges by devising strategies for the generation and curation of high-throughput data, developing novel integrative algorithms and models for interrogating specific aspects of aging biology, including the role of cellular heterogeneity, and implementing these models via an accessible online portal. The Modeling Core proposes the following three specific aims. First, the Core will establish sufficient data infrastructure. Integrative modeling requires high quality pre-processed data obtained from diverse high- throughput assays. This Aim will identify and implement the hardware and software resources required to pre- process and store sequencing, proteomics, metabolomics, and imaging data. Second, the Core will implement and develop integrative models of aging that take into account the heterogenicity of the process. Integrative computational models will enable the mapping of diverse pre-processed data inputs into integrated interpretable biological processes. These models can then be used to generate hypotheses that can be tested in the lab, resulting in the generation of additional datasets, which can be used to refine the models in an iterative manner. Work in this aim will consist of: 1) fulfilling requests to apply established techniques for the integrative analysis of data, and 2) developing customized predictive computational models as tools for answering specific questions regarding aging biology. Finally, the Core will provide widespread access to integrative modeling tools. While computational models allow for a systematic understanding of specific aging- related biological processes, widespread access to these models will be needed to maximize impact across NSCs and across the field of aging. This aim is focused on translating the models and theories into interactive tools for use by aging biology researchers.