RESUMO
We introduce a new approach to inference for subgroups in clinical trials. We use Bayesian model selection, and a threshold on posterior model probabilities to identify subgroup effects for reporting. For each covariate of interest, we define a separate class of models, and use the posterior probability associated with each model and the threshold to determine the existence of a subgroup effect. As usual in Bayesian clinical trial design we compute frequentist operating characteristics, and achieve the desired error probabilities by choosing an appropriate threshold(s) for the posterior probabilities.
Assuntos
Teorema de Bayes , Ensaios Clínicos como Assunto/estatística & dados numéricos , Feminino , Humanos , Masculino , Modelos EstatísticosRESUMO
MOTIVATION: Identifying groups of co-regulated genes by monitoring their expression over various experimental conditions is complicated by the fact that such co-regulation is condition-specific. Ignoring the context-specific nature of co-regulation significantly reduces the ability of clustering procedures to detect co-expressed genes due to additional 'noise' introduced by non-informative measurements. RESULTS: We have developed a novel Bayesian hierarchical model and corresponding computational algorithms for clustering gene expression profiles across diverse experimental conditions and studies that accounts for context-specificity of gene expression patterns. The model is based on the Bayesian infinite mixtures framework and does not require a priori specification of the number of clusters. We demonstrate that explicit modeling of context-specificity results in increased accuracy of the cluster analysis by examining the specificity and sensitivity of clusters in microarray data. We also demonstrate that probabilities of co-expression derived from the posterior distribution of clusterings are valid estimates of statistical significance of created clusters. AVAILABILITY: The open-source package gimm is available at http://eh3.uc.edu/gimm.
