Mixture distributions with application to microarray data analysis

The main goal in analyzing microarray data is to determine the genes that are differentially expressed across two types of tissue samples or samples obtained under two experimental conditions. In this dissertation we proposed two methods to determine differentially expressed genes. For the penalized normal mixture model (PMMM) to determine genes that are differentially expressed, we penalized both the variance and the mixing proportion parameters simultaneously. The variance parameter was penalized so that the log-likelihood will be bounded, while the mixing proportion parameter was penalized so that its estimates are not on the boundary of its parametric space. The null distribution of the likelihood ratio test statistic (LRTS) was simulated so that we could perform a hypothesis test for the number of components of the penalized normal mixture model. In addition to simulating the null distribution of the LRTS for the penalized normal mixture model, we showed that the maximum likelihood estimates were asymptotically normal, which is a first step that is necessary to prove the asymptotic null distribution of the LRTS. This result is a significant contribution to field of normal mixture model. The modified p-value approach for detecting differentially expressed genes was also discussed in this dissertation. The modified p-value approach was implemented so that a hypothesis test for the number of components can be conducted by using the modified likelihood ratio test. In the modified p-value approach we penalized the mixing proportion so that the estimates of the mixing proportion are not on the boundary of its parametric space. The null distribution of the (LRTS) was simulated so that the number of components of the uniform beta mixture model can be determined. Finally, for both modified methods, the penalized normal mixture model and the modified p-value approach were applied to simulated and real data