Core 3: Integrative Models of Aging Core

核心3：老化核心的综合模型

• 批准号: 10665593
• 负责人: Tatyana O. SHARPEE
• 金额: $ 14.37万
• 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/10665593
• 关键词: Age; Aging; Algorithms; Biological Process; Biology of Aging; Computer Models; Computer software; Data; Data Analyses; Data Set; Disparate; 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; data integration; 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.

项目总结-老化核心的综合模型 老龄化是一个多方面、多尺度、异质性的过程。虽然特定的途径和基因 与老龄化相关的研究开始从计算建模研究中脱颖而出，在高度... 产量和单细胞测序、蛋白质组学和成像分析，老龄化领域的研究人员必须 克服许多挑战来集成和解释这些不同的、通常是海量的数据集。 由于进入门槛很高，衰老生物学的研究人员才刚刚开始接近 使用集成的数据驱动方法进行老化。以支持圣地亚哥内森休克中心的使命 衰老基础生物学(SD-NSC)--衰老核(模型核)的综合模型 将通过制定产生和管理高通量数据的战略来应对这些挑战， 开发用于询问衰老生物学的特定方面的新的综合算法和模型， 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。这个 建模核心提出了以下三个具体目标。首先，核心将建立足够的数据 基础设施。综合建模需要从不同的高精度数据中获得高质量的预处理数据 吞吐量分析。这一目标将确定和实施预配置所需的硬件和软件资源 处理和存储测序、蛋白质组学、代谢组学和成像数据。第二，核心将实施 并开发综合的老化模型，考虑到过程的异质性。集成式 计算模型将能够将不同的预处理数据输入映射到综合数据 可解释的生物过程。然后，可以使用这些模型来生成可以检验的假设 在实验室中，导致生成额外的数据集，这些数据集可用于改进 迭代方式。这一目标的工作将包括：1)满足将既定技术应用于 数据的综合分析，以及2)开发定制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，核心将提供广泛的访问 集成的建模工具。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，将需要广泛获得这些模型，以最大限度地影响 NSCs和整个老龄化领域。这个目标集中在将模型和理论转化为交互 供年迈的生物学研究人员使用的工具。