Advanced search
122
Views
4
CrossRef citations to date
0
Altmetric
Original Articles

Bayesian Analysis of A Rat Formaldehyde DNA–Protein Cross-Link Model

, , , &
Pages 787-806
Received 29 Oct 2009
Accepted 30 Jan 2010
Published online: 07 Apr 2010

As the initial effort in a multi-step uncertainty analysis of a biologically based cancer model for formaldehyde, a Markov chain Monte Carlo (MCMC) analysis was performed for a compartmental model that predicts DNA–protein cross-links (DPX) produced by formaldehyde exposure. The Bayesian approach represented by the MCMC analysis integrates existing knowledge of the model parameters with observed, formaldehyde-DPX-specific data, providing a statistically sound basis for estimating model output uncertainty. Uncertainty and variability were evaluated through a hierarchical structure, where interindividual variability was considered for all model parameters and that variability was assumed to be uncertain on population levels. The uncertainty of the population mean and that of the population variance were significantly reduced through the MCMC analysis. Our investigation highlights several issues that must be dealt with in many real-world analyses (e.g., issues of parameters' nonidentifiability due to limited data) while demonstrating the feasibility of conducting a comprehensive quantitative uncertainty evaluation. The current analysis can be viewed as a case study, for a relatively simple model, illustrating some of the constraints that analysts will face when applying Bayesian approaches to biologically or physiologically based models of increasing complexity.

The authors thank Drs. Rory Conolly, Julia Kimbell, Andy Nong, Jerry Campbell, and Miyoung Yoon and Betsy Gross Bermudez for their valuable reviews and comments. This work was supported by the Formaldehyde Council, Inc.

Present address for Yu-Mei Tan is U.S. Environmental Protection Agency, National Exposure Research Laboratory, Research Triangle Park, NC 27711, USA. Present address for Kai H. Liao is Drug Safety and Metabolism, Wyeth Research, 401 N. Middletown Rd, Pearl River, NY 10965, USA.

 

Related research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.