A new mixture model approach to analyzing allelic-loss data using Bayes factors

Abstract

Background: Allelic-loss studies record data on the loss of genetic material in tumor tissue relative to normal tissue at various loci along the genome. As the deletion of a tumor suppressor gene can lead to tumor development, one objective of these studies is to determine which, if any, chromosome arms harbor tumor suppressor genes.

Results: We propose a large class of mixture models for describing the data, and we suggest using Bayes factors to select a reasonable model from the class in order to classify the chromosome arms. Bayes factors are especially useful in the case of testing that the number of components in a mixture model is n0 versus n1. In these cases, frequentist test statistics based on the likelihood ratio statistic have unknown distributions and are therefore not applicable. Our simulation study shows that Bayes factors favor the right model most of the time when tumor suppressor genes are present. When no tumor suppressor genes are present and background allelic-loss varies, the Bayes factors are often inconclusive, although this results in a markedly reduced false-positive rate compared to that of standard frequentist approaches. Application of our methods to three data sets of esophageal adenocarcinomas yields interesting differences from those results previously published.

Conclusions: Our results indicate that Bayes factors are useful for analyzing allelic-loss data.

Figure 1

Histogram of allelic loss for the Barrett data set

Figure 2

Histogram of allelic loss for the Gleeson data set

Figure 3

Histogram of allelic loss for the Hammoud data set