论文标题

推断暴露混合物中的协同和拮抗相互作用

Inferring Synergistic and Antagonistic Interactions in Mixtures of Exposures

论文作者

Chattopadhyay, Shounak, Engel, Stephanie M., Dunson, David

论文摘要

评估多种暴露对人类健康的共同影响具有丰富的兴趣。这通常被称为环境流行病学和毒理学中的混合物问题。从经典上讲,研究一次检查了一种不同化学物质的不良健康影响,但人们担心某些化学物质可能会共同起作用以扩大彼此的影响。这种扩增被称为协同相互作用,而抑制彼此效应的化学物质具有拮抗相互作用。当前评估化学混合物健康影响的方法并未明确考虑建模中的协同作用或拮抗作用,而是专注于参数或无约束的非参数剂量反应表面建模。参数情况可能过于僵化,而非参数方法则面临着维度的诅咒,导致过度摇摆不定的表面估计。我们提出了一种贝叶斯方法,将响应表面分解为添加剂主要效应和成对相互作用效应,然后检测到协同和拮抗的相互作用。还提供了每个相互作用组件的可变选择决策。使用仿真实验和对NHANES数据的应用,对现有方法进行了评估,对现有方法评估了这种协同的拮抗互动检测(上述)框架。

There is abundant interest in assessing the joint effects of multiple exposures on human health. This is often referred to as the mixtures problem in environmental epidemiology and toxicology. Classically, studies have examined the adverse health effects of different chemicals one at a time, but there is concern that certain chemicals may act together to amplify each other's effects. Such amplification is referred to as synergistic interaction, while chemicals that inhibit each other's effects have antagonistic interactions. Current approaches for assessing the health effects of chemical mixtures do not explicitly consider synergy or antagonism in the modeling, instead focusing on either parametric or unconstrained nonparametric dose response surface modeling. The parametric case can be too inflexible, while nonparametric methods face a curse of dimensionality that leads to overly wiggly and uninterpretable surface estimates. We propose a Bayesian approach that decomposes the response surface into additive main effects and pairwise interaction effects, and then detects synergistic and antagonistic interactions. Variable selection decisions for each interaction component are also provided. This Synergistic Antagonistic Interaction Detection (SAID) framework is evaluated relative to existing approaches using simulation experiments and an application to data from NHANES.

扫码加入交流群

加入微信交流群

微信交流群二维码

扫码加入学术交流群,获取更多资源