TRAB: Testing Whether Mutation Frequencies Are Above an Unknown Background

To rigorously determine whether a gene or a set of genes have alterations that are involved in carcinogenesis requires a comparison of the prevalence of identified changes to a control mutation frequency present in tumor DNA. To facilitate this task, we develop a testing approach and the associated R library, called TRAB, that evaluates whether the frequency of somatic mutation in a given gene is higher than that observed in a control group of genes. Specifically, we test the null hypothesis that the frequency belongs to a control population of frequencies, against the alternative hypothesis that the frequency is higher. Mutation frequencies in the control group are themselves allowed to be variable. TRAB computes the a posteriori probability and the Bayes factor for the hypothesis using a hierarchical Bayesian approach.