马什:生存结果的调解分析和高维度的OMICS调解者与复杂疾病的应用
Sunyi Chi1, Christopher R Flowers2, Ziyi Li1
1Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
The annals of applied statistics
|September 27, 2024
概括
环境暴露通过分子变化影响健康. 我们开发了MASH,这是一种新方法来分析高维的奥米克数据,以确定中介对生存结果的影响,并确定关键的分子中介.
科学领域:
- * 环境健康科学 环境健康科学
- * 生物统计学
- * 基因组学和奥米学
背景情况:
- *环境暴露,如吸烟,通过分子变化 (甲基组,转录组,代谢组) 影响健康.
- *调解分析有助于理解这些分子通路,但面临着高维的奥米克数据和生存结果的挑战.
- *现有的方法缺乏对使用高维介质的生存分析中总调解效应的可靠测量.
研究的目的:
- * 提出一种新的统计程序,MASH (Mediation Analysis of Survival outcome and High-dimensional omics mediators),用于分析在生存中介分析中的高维的奥米克数据.
- * 引入对生存数据的总中介效应的强有力的测量方法,类似于线性模型中的R平方.
- * 为了能够识别将环境暴露与生存结果联系起来的分子媒介.
主要方法:
- * 开发了MASH,结合了确定独立性选,从高维的奥米克数据中选择相关的介质变量.
- *采用基于第二时刻的测量方法来量化生存终点的总中介效应.
- *通过广泛的模拟验证了该方法,并将其应用于现实世界数据集 (弗雷明汉心脏研究,淋巴瘤数据).
主要成果:
- *模拟证明了MASH在准确估计总调解效果和识别真正的分子调解者的有效性.
- * 在弗雷明汉心脏研究中,MASH确定了五种代谢物调解吸烟对冠心病的影响 (总调解率为51.1%) 和两种癌症风险 (总调解率为50.7%).
- *对淋巴瘤数据的分析揭示了8种基因拷贝数变异,调解了国际预后指数和整体存活率之间的关系.
结论:
- *MASH提供了一个强大的框架,用于通过高维的奥米克数据对生存结果的调解分析.
- * 该方法成功地确定了与吸烟相关的健康结果和癌症风险的特定分子媒介.
- *MASH提供了一种有价值的工具,用于剖析各种生物环境中复杂的环境暴露与健康结果关系.
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