In-silico evaluation of aging-related interventions using omics data and predictive modeling

IF 12.4 1区 医学 Q1 CELL BIOLOGY
Georg Fuellen , Daniel Palmer , Claudia Fruijtier , Roberto A. Avelar
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引用次数: 0

Abstract

A major challenge in aging research is identifying interventions that can improve lifespan and health and minimize toxicity. Clinical studies cannot usually consider decades-long follow-up periods, and therefore, in-silico evaluations using omics-based surrogate biomarkers are emerging as key tools. However, many current approaches train predictive models on observational data, rather than on intervention data, which can lead to biased conclusions. Yet, the first classifiers for lifespan extension by compounds are now available, learned on intervention data. Here, we review evaluation methodologies and we prioritize training on intervention data whenever available, highlight the importance of safety and toxicity assessments, discuss the role of standardized benchmarks, and present a range of feature processing and predictive modeling approaches. We consider linear and non-linear methods, automated machine learning workflows, and use of AI. We conclude by emphasizing the need for explainable and reproducible strategies, the integration of safety metrics, and the careful validation of predictors based on interventional benchmarks.
使用组学数据和预测模型的衰老相关干预措施的计算机评估。
老龄化研究的一个主要挑战是确定可以延长寿命和健康并将毒性降到最低的干预措施。临床研究不能考虑长达数十年的随访期,因此,使用基于组学的替代生物标志物的计算机评估正在成为关键工具。然而,目前的许多方法都是根据观测数据而不是干预数据来训练预测模型,这可能导致有偏见的结论。然而,根据干预数据,化合物延长寿命的第一个分类器现在是可用的。在这里,我们回顾了评估方法,并在可用的情况下优先考虑干预数据的培训,强调安全性和毒性评估的重要性,讨论了标准化基准的作用,并提出了一系列特征处理和预测建模方法。我们考虑线性和非线性方法,以及自动化机器学习工作流程。最后,我们强调需要可解释和可重复的策略,安全指标的整合,以及基于干预基准的预测因子的仔细验证。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Ageing Research Reviews
Ageing Research Reviews 医学-老年医学
CiteScore
19.80
自引率
2.30%
发文量
216
审稿时长
55 days
期刊介绍: With the rise in average human life expectancy, the impact of ageing and age-related diseases on our society has become increasingly significant. Ageing research is now a focal point for numerous laboratories, encompassing leaders in genetics, molecular and cellular biology, biochemistry, and behavior. Ageing Research Reviews (ARR) serves as a cornerstone in this field, addressing emerging trends. ARR aims to fill a substantial gap by providing critical reviews and viewpoints on evolving discoveries concerning the mechanisms of ageing and age-related diseases. The rapid progress in understanding the mechanisms controlling cellular proliferation, differentiation, and survival is unveiling new insights into the regulation of ageing. From telomerase to stem cells, and from energy to oxyradical metabolism, we are witnessing an exciting era in the multidisciplinary field of ageing research. The journal explores the cellular and molecular foundations of interventions that extend lifespan, such as caloric restriction. It identifies the underpinnings of manipulations that extend lifespan, shedding light on novel approaches for preventing age-related diseases. ARR publishes articles on focused topics selected from the expansive field of ageing research, with a particular emphasis on the cellular and molecular mechanisms of the aging process. This includes age-related diseases like cancer, cardiovascular disease, diabetes, and neurodegenerative disorders. The journal also covers applications of basic ageing research to lifespan extension and disease prevention, offering a comprehensive platform for advancing our understanding of this critical field.
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