Machine learning based frailty index for the genetically diverse mice

基于机器学习的遗传多样性小鼠的衰弱指数

• 批准号: 10513177
• 负责人: VIVEK KUMAR
• 金额: $ 33.6万
• 依托单位: JACKSON LABORATORY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10513177
• 关键词: Adopted; Affect; Age; Aging; Animal Model; Animals; Applied Research; Automation; Basic Science; Behavior; Behavioral; Behavioral Model; Biological; Biological Aging; Biological Assay; Caloric Restriction; Chronic; Chronology; Clinical; Collaborations; Computer Vision Systems; Data; Data Set; Diet; Dietary Intervention; Disease; Environmental Risk Factor; Etiology; Fatty acid glycerol esters; Future; Genetic; Gerontology; Health; Health Status; Heterogeneity; High Fat Diet; Hour; Human; Individual; Intervention; Intervention Studies; Judgment; Letters; Longevity; Machine Learning; Manuals; Measures; Methods; Monitor; Mouse Strains; Mus; Nesting Behavior; Organism; Outcome; Phase; Phenotype; Physiological; Physiology; Population; Population Heterogeneity; Process; Public Health; Reproducibility; Research; Shock; Sleep; Social Behavior; System; Testing; The Jackson Laboratory; Therapeutic; Time; Training; Translational Research; Visual; age related; aged; base; biological systems; clinical heterogeneity; dietary restriction; diverse data; drinking behavior; feeding; frailty; hands-on learning; healthy aging; high reward; high risk; human model; improved; indexing; machine learning model; mortality; mortality risk; novel; open field behavior; pre-clinical; preclinical study; social; sugar; tool; translational study

PROJECT SUMMARY Aging is a terminal process that affects all biological systems. Biological aging—in contrast to chronological aging—occurs at different rates for different individuals. In humans, growing old comes with increased health issues and mortality rates, yet some individuals live long and healthy lives, and others succumb earlier to diseases and disorders. The concept of frailty is used to quantify this heterogeneity and is defined as the state of increased vulnerability to adverse health outcomes. The frailty index (FI) is an invaluable and widely used tool which outperforms other methods to quantify frailty. FIs have been adapted for use in mice using a variety of both behavioral and physiological measures as index items. However, because conducting mouse FI requires trained individuals for manual scoring, it often limits the scalability of the tool. Thus, although the FI is an extremely useful tool for aging research, an increase in its scalability, reliability, and reproducibility through automation would enhance its utility. We used machine learning applied to video data to create an automated visual FI (vFI). The is easy to implement, unbiased, and scalable. Here we propose to improve our tool and carry out an interventional study. We will adopt the vFI to function with genetically diverse mice (R61: Aim 1). We will also create features from long-term monitoring to increase accuracy and breadth of systems measured in the vFI (R61: Aim 2). Finally, we will apply the vFI to a diet intervention study to show its utility for large scale studies (R33: Aim 3). We will test a high fat high sugar diet (increased frailty) and caloric restriction group (decreased frailty) with normal chow (control) in a Diversity Outbred population of mice. The result of this project will be a fully validated and automated vFI that can be used for high-throughput interventional studies, enabling therapeutics for healthy aging.

项目摘要 衰老是一个影响所有生物系统的终端过程。生物老化-与时间老化相反 老化--对于不同的个体以不同的速率发生。在人类中，随着年龄的增长，健康状况也会增加 问题和死亡率，但有些人活得长，健康的生活，和其他人屈服于更早， 疾病和失调。脆弱性的概念被用来量化这种异质性，并被定义为状态 对不利健康结果的脆弱性增加。虚弱指数（FI）是一个非常宝贵和广泛使用的工具 它优于其他方法来量化脆弱性。FI已经被调整用于使用多种方法的小鼠中。 行为和生理测量作为指标项目。然而，由于进行鼠标FI需要 人工评分的培训人员，它往往限制了工具的可扩展性。虽然，这是一个 一个非常有用的工具，老化研究，增加其可扩展性，可靠性和再现性，通过 自动化将提高其效用。我们将机器学习应用于视频数据， 视觉FI（vFI）。易于实现、无偏差且可扩展。在这里，我们建议改善我们的工具和携带 进行一项干预性研究。我们将采用vFI对遗传多样性小鼠发挥作用（R61：目标1）。我们将 还从长期监测中创建功能，以提高系统测量的准确性和广度， vFI（R61：目标2）。最后，我们将应用vFI的饮食干预研究，以显示其效用的大规模研究 (R33目标3）。我们将测试高脂肪高糖饮食（增加虚弱）和热量限制组（减少 虚弱）与正常食物（对照）在多样性远交小鼠群体中进行比较。该项目的结果将是一个 完全验证和自动化的vFI，可用于高通量介入研究， 健康老龄化的治疗方法。