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.
bioRxiv : the preprint server for biology
|September 4, 2023
概括
环境暴露通过分子变化影响健康. 我们开发了MASH,这是一种分析高维奥米克数据以调解生存结果的方法,成功地识别了吸烟相关疾病的调解者.
科学领域:
- 生物统计学 生物统计学
- 基因组学就是基因组学.
- 环境健康 环境健康
背景情况:
- 环境暴露通过分子变化 (甲基组,转录组,代谢组) 影响健康.
- 调解分析探讨了这些中间表型,但缺乏用于高维欧米克数据和生存结果的方法.
- 需要对生存数据的总中介效应进行强有力的测量.
研究的目的:
- 提出一种新的统计方法,MASH (生存结果的调解分析和高维的奥米克调解器).
- 为了能够对具有生存终点的高维欧米克数据的总调解效应进行可靠的估计.
- 确定特定的分子介质,将环境暴露与健康结果联系起来.
主要方法:
- 开发了MASH,在调解人选择中结合了确定的独立性选.
- 引入了一种基于第二个时刻的测量方法,用于对生存数据的总中介效应.
- 通过广泛的模拟验证了MASH,并将其应用于现实世界的数据集.
主要成果:
- 在模拟中,MASH在估计调解效应和识别真正的调解者方面表现强.
- 应用到Framingham心脏研究的代谢学数据,MASH确定了调解吸烟对冠心病和癌症风险的影响的关键代谢物.
- 对淋巴瘤基因组学数据的分析揭示了基因拷贝数变异,调解了预后得分对生存的影响.
结论:
- MASH为调解分析提供了一个强大的框架,提供了高维的奥米克数据和生存结果.
- 该方法成功地确定了与吸烟相关的疾病风险和癌症的分子媒介.
- 在OMICS研究中,MASH为理解复杂的环境暴露与健康结果关系提供了有价值的工具.
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