A Bayesian analysis of colonic crypt structure and coordinated response to carcinogen exposure incorporating missing crypts
A Bayesian analysis of colonic crypt structure and coordinated response to carcinogen exposure incorporating missing crypts
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DOI：
10.1093/biostatistics/3.4.529
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发表时间：
2002-12-01
期刊：
影响因子：
2.1
通讯作者：
Carroll, RJ
中科院分区：
文献类型：
--
作者：
Morris, JS;Wang, NY;Carroll, RJ
本文对结肠隐窝的结构进行了建模，并探讨了该建模对于理解致癌物诱导的DNA损伤在结肠不同区域之间可能的协调反应的意义。我们开发的解决这两个问题的方法被应用于结肠癌发生中的一个特别重要的例子。我们把这个问题描述为一种不寻常的、以前没有研究过的分层混合效应模型，其特征是除了一些随机选择的单元外，在结构上基本水平的单元中完全缺少协变量。关于缺失协变量的信息可以通过某些已知的排序约束和替代措施来获得。我们的方法使用贝叶斯机制。我们利用这个问题的生物结构来同时有效地在基本水平上产生缺失的协变量，而不是用Metropolis-Hastings步骤在基本水平上一次一个地产生单元的天真做法。我们应用我们的方法来证明结肠的不同区域具有不同的结构，并估计一个重要但非标准的函数，该函数衡量结肠不同区域DNA损伤机制的相互关系。
This paper is concerned with modeling the architecture of colonic crypts and the implications of this modeling for understanding possible coordinated response of carcinogen-induced DNA damage between various regions of the colon. The methods we develop to address these two issues are applied to a particular important example in colon carcinogenesis. We cast the problem as an unusual and not previously studied hierarchical mixed-effects model characterized by completely missing covariates in units at a structurally base level, except for some randomly selected units. Information concerning the missing covariates is available through certain known ordering constraints and surrogate measures. Our methods use Bayesian machinery. We exploit the biological structure of this problem to generate the missing covariates simultaneously and efficiently at the base levels, as opposed to the naive practice of generating units at the base levels one-at-a-time with Metropolis-Hastings steps. We apply our methods to show that different regions of the colon have different architectures, and to estimate an important but nonstandard function that measures the interrelationship of DNA damage mechanisms in different regions of the colon.