Core 3: Integrative Models of Aging Core

核心3：老化核心的综合模型

• 批准号: 10410542
• 负责人: Tatyana O. SHARPEE
• 金额: $ 14.36万
• 依托单位: SALK INSTITUTE FOR BIOLOGICAL STUDIES
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-30 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10410542
• 关键词: Address; Age; Aging; Algorithms; Biological Process; Biology of Aging; Computer Models; Computer software; Custom; Data; Data Analyses; Data Set; Generations; Genes; Heterogeneity; Image; Maps; Mission; Modeling; Pathway interactions; Process; Proteomics; Research; Research Personnel; Resources; Role; Shock; Study models; Techniques; Testing; Translating; Work; data infrastructure; high throughput screening; interactive tool; metabolomics; novel; single cell sequencing; theories; tool; web portal

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.

项目摘要 - 老化核心的综合模型 衰老是一个多方面的，多尺度和异质过程。而特定的途径和基因 与衰老相关的是，在高 - 吞吐量和单细胞测序，蛋白质组学和成像分析，衰老领域的研究人员必须 克服整合和解释这些不同且常常大量数据集的许多挑战。 由于进入的障碍很高，老龄化研究人员的生物学才开始研究 使用集成数据驱动的方法衰老。支持圣地亚哥内森冲击中心的任务 老化基本生物学（SD-NSC）的卓越表现，衰老核心的综合模型（建模核心） 通过制定高通量数据的生成和策略来解决这些挑战， 开发新颖的综合算法和模型来询问衰老生物学的特定方面， 包括细胞异质性的作用，并通过可访问的在线门户实施这些模型。 对核心建议进行建模以下三个特定目标。首先，核心将建立足够的数据 基础设施。综合建模需要从高质量的高质量预处理数据 吞吐量测定。此目标将确定并实施预先预先的硬件和软件资源 过程和存储测序，蛋白质组学，代谢组学和成像数据。第二，核心将实施 并开发衰老的综合模型，这些模型考虑了该过程的异质性。综合 计算模型将使各种预处理的数据输入能够映射到集成的 可解释的生物过程。然后可以使用这些模型来生成可以测试的假设 在实验室中，导致生成其他数据集，可用于完善模型 迭代方式。此目的的工作将包括：1）满足为应用既定技术的要求 数据的综合分析，以及2）开发自定义的预测计算模型作为工具 回答有关衰老生物学的具体问题。最后，核心将提供对宽度的访问 集成建模工具。虽然计算模型允许系统地了解特定的衰老 - 相关的生物过程，将需要宽度访问这些模型，以最大程度地发挥影响力 NSC和整个衰老领域。这个目标专注于将模型和理论转化为互动 老化生物学研究人员使用的工具。