April, 2005
Single-cell electrophoresis (comet assay) can be used to study DNA damage and repair mechanisms by measuring the frequency of strand breaks for individual cells in samples collected before and after exposure to a genotoxic agent. Because the distributions of the surrogates of DNA damage across cells in a sample vary in shape for different cell lines and follow-up times, standard hierarchical models are not adequate. We develop a Bayesian approach based on a finite mixture of normals that allows the mixture weights to shift dynamically with repair time and cell lines. Specifically, the weights are assigned a hierarchical model that includes a factor structure with cell-line-specific latent traits measuring baseline damage, susceptibility to induced damage, and rate of DNA repair. Methods are developed for assessing heterogeneity among individuals in these traits, while also identifying DNA repair gene polymorphisms. Preliminary results demonstrate clear evidence of heterogeneity in rates of DNA damage and repair across cell lines, possibly due in part to polymorphisms in repair genes such as POLG, XRCC3, POLD1, and ERCC1.
Keywords: Comet assay; Factor analysis; Finite mixture model; Hierarchical model; MCMC algorithm; Molecular epidemiology; Stochastic search, Test of homogeneity.
The manuscript is available in PDF formats.