| Genome research advances of the last two decades allow us to obtain various forms of data, such as next-generation sequencing, genotyping, phenotyping, as well as clinical information. However, our ability to derive useful information from these data remains to be improved. This motivated me to develop a pipeline with new computational methods. In this dissertation, I develop, implement, evaluate, and apply statistical and computational methods for high-dimensional data analysis to facilitate efforts in regenerative medicine and to uncover novel insights in cancer genomics.;The first method is an integrative pathway-index (IPI) model to identify a clinically actionable biomarker of high-risk advanced ovarian cancer patients. Despite improvements in operative management and therapies, overall survival rates in advanced ovarian cancer have remained largely unchanged over the past three decades. The IPI model is applied to messenger RNA expression and survival data collected on ovarian cancer patients as part of the Cancer Genome Atlas project. The approach identifies signatures that are strongly associated with overall and progression-free survival, and also identifies group of patients who may benefit from enhanced adjuvant therapy.;The second method is called SCDC for removing increased variability due to oscillating genes in a snapshot scRNA-seq experiment. Single-cell RNA sequencing provides a new avenue for studying oscillatory gene expression. However, in many studies, oscillations (e.g., cell cycle) are not of interest, and the increased variability imposed by them masks the effects of interest. In bulk RNA-seq, the increase in variability caused by oscillatory genes is mitigated by averaging over thousands of cells. However, in typical unsynchronized scRNA-seq, this variability remains. Simulation and case studies demonstrate that by removing increased variability due to oscillations, both the power and accuracy of downstream analysis is increased.;Finally, in this thesis, we have extended a data analysis pipeline for both single- cell and bulk RNA-seq data. In this pipeline, we review current standards and resources for (sc)RNA-seq data analysis and provide an extended pipeline that incorporates a quality control scheme and user friendly advanced statistical analysis software for visualization and projected principal component analysis (PCA). |
