Application of Bayesian Modeling in High-throughput Genomic Data and Clinical Trial Design
Cox, Dennis D.; Ji, Yuan
Doctor of Philosophy
My dissertation mainly focuses on developing Bayesian models for high-throughput data and clinical trial design. Next-generation sequencing (NGS) technology generates millions of short reads, which provide valuable information for various aspects of cellular activities and biological functions. So far, NGS techniques have been applied in quantitatively measurement of diverse platforms, such as RNA expression, DNA copy number variation (CNV) and DNA methylation. Although NGS is powerful and largely expedite biomedical research in various fields, challenge still remains due to the high modality of disparate high-throughput data, high variability of data acquisition, high dimensionality of biomedical data, and high complexity of genomics and proteomics, e.g., how to extract useful information for the enormous data produced by NGS or how to effectively integrate the information from different platforms. Bayesian has the potential to fill in these gaps. In my dissertation, I will propose Bayesian-based approaches to address above challenges so that we can take full advantage of the NGS technology. It includes three specific topics: (1) proposing BM-Map: a Bayesian mapping of multireads for NGS data, (2) proposing a Bayesian graphical model for integrative analysis of TCGA data, and (3) proposing a non- parametric Bayesian Bi-clustering for next generation sequencing count data. For the clinical trial design, I will propose a latent Gaussian process model with application to monitoring clinical trials.