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This thesis presents simple efficient algorithms to estimate distribution parameters and to construct prediction intervals for location-scale families. Specifically, we study two scenarios: one is a frequentist method for a general location--scale family and then extend to a 3-parameter distribution, another is a Bayesian method for the Gumbel distribution. At the end of the thesis, a generalized bootstrap resampling scheme is proposed to construct prediction intervals for data with an unknown distribution. Our estimator construction begins with the equivariance principle, and then makes use of unbiasedness principle. These two estimates have closed form and are functions of the sample mean, sample standard deviation, sample size, as well as the mean and variance of a corresponding standard distribution. Next, we extend the previous result to estimate a 3-parameter distribution which we call a mixed method. A central idea of the mixed method is to estimate the location and scale parameters as functions of the shape parameter. The sample mean is a popular estimator for the population mean. The mean squared error (MSE) of the sample mean is often large, however, when the sample size is small or the scale parameter is greater than the location parameter. To reduce the MSE of our location estimator, we introduce an adaptive estimator. We will illustrate this by the example of the power Gumbel distribution. The frequentist approach is often criticized as failing to take into account the uncertainty of an unknown parameter, whereas a Bayesian approach incorporates such uncertainty. The present Bayesian analysis for the Gumbel data is achieved numerically as it is hard to obtain an explicit form. We tackle the problem by providing an approximation to the exponential sum of Gumbel random variables. Next, we provide two efficient methods to construct prediction intervals. The first one is a Monte Carlo method for a general location-scale family, based on our previous parameter estimation. Another is the Gibbs sampler, a special case of Markov Chain Monte Carlo. We derive the predictive distribution by making use of an approximation to the exponential sum of Gumbel random variables . Finally, we present a new generalized bootstrap and show that Efron's bootstrap re-sampling is a special case of the new re-sampling scheme. Our result overcomes the issue of the bootstrap of its ``inability to draw samples outside the range of the original dataset.'' We give an applications for constructing prediction intervals, and simulation shows that generalized bootstrap is better than that of the bootstrap when the sample size is small. The last contribution in this thesis is an improved GRS method used in nuclear engineering for construction of non-parametric tolerance intervals for percentiles of an unknown distribution. Our result shows that the required sample size can be reduced by a factor of almost two when the distribution is symmetric. The confidence level is computed for a number of distributions and then compared with the results of applying the generalized bootstrap. We find that the generalized bootstrap approximates the confidence level very well. / Dissertation / Doctor of Philosophy (PhD)

The rapid development of biotechnology has enabled researchers to collect high-throughput data for studying various biological processes at the genomic level, transcriptomic level, and proteomic level. Due to the large noise in the data and the high complexity of diseases (such as cancer), it is a challenging task for researchers to extract biologically meaningful information that can help reveal the underlying molecular mechanisms. The challenges call for more efforts in developing efficient and effective computational methods to analyze the data at different levels so as to understand the biological systems in different aspects. In this dissertation research, we have developed novel Bayesian approaches to infer alternative splicing mechanisms in biological systems using RNA sequencing data. Specifically, we focus on two research topics in this dissertation: isoform identification and phenotype-specific transcript assembly. For isoform identification, we develop a computational approach, SparseIso, to jointly model the existence and abundance of isoforms in a Bayesian framework. A spike-and-slab prior is incorporated into the model to enforce the sparsity of expressed isoforms. A Gibbs sampler is developed to sample the existence and abundance of isoforms iteratively. For transcript assembly, we develop a Bayesian approach, IntAPT, to assemble phenotype-specific transcripts from multiple RNA sequencing profiles. A two-layer Bayesian framework is used to model the existence of phenotype-specific transcripts and the transcript abundance in individual samples. Based on the hierarchical Bayesian model, a Gibbs sampling algorithm is developed to estimate the joint posterior distribution for phenotype-specific transcript assembly. The performances of our proposed methods are evaluated with simulation data, compared with existing methods and benchmarked with real cell line data. We then apply our methods on breast cancer data to identify biologically meaningful splicing mechanisms associated with breast cancer. For the further work, we will extend our methods for de novo transcript assembly to identify novel isoforms in biological systems; we will incorporate isoform-specific networks into our methods to better understand splicing mechanisms in biological systems. / Ph. D.