Date of Award

2019

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biology

Abstract

This study is to characterize and quantify regulatory changes in the cancer regulatory network, which includes factors such as alternative splicing (AS) and miRNA-mRNA interaction. To achieve this goal, we compare, develop, and evaluate tools to identify AS splicing junction. We also develop pipelines to characterize, cluster, and visualize miRNA-mRNA pairs in tumor tissues compared to normal tissues. With the tools or pipelines, researchers can characterize and quantify molecular level changes in the tumorous tissues compared to normal tissues in different cancer types. This study provides new hallmarks of cancer types, potential diagnostic biomarkers, and therapeutic targets in cancer and can improve the personalized medicine with the advance of the personal sequencing. This study is organized into eight chapters. The first chapter gives a brief introduction of the background of the research. The second chapter introduces cancer genetics and bioinformatics tools by reviewing AS detection tools. The third chapter develops and evaluates the AS detection tools (Read-Split-Run). The fourth chapter develops and evaluates AS detection tools (Read-Split-Fly). The fifth chapter dissects and visualizes biological relationships between miRNA and mRNA using The Cancer Genome Atlas (TCGA) data (MMiRNA-Viewer 1). The sixth chapter involves identifying gene and miRNA interaction clusters and visualizing functional annotation of miRNA-mRNA pairs (MMiRNA-Viewer 2). The seventh chapter develop algorithms to cluster the miRNA and mRNA based on their correlation change from normal to tumor by applying Hungarian-Blossom algorithm (MWMM). The eighth chapter summarizes the research and discusses potential future study direction.

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