Indiana University-Purdue University Indianapolis (IUPUI) / In eukaryotes, genetic information is encoded by DNA, transcribed to precursor
messenger RNA (pre-mRNA), processed into mature messenger RNA (mRNA), and
translated into functional proteins. Splicing of pre-mRNA is an important epigenetic
process that alters the function of proteins through modifying the exon structure of
mature mRNA transcripts and is known to greatly contribute to diversity of the human
proteome. The vast majority of human genes are expressed through multiple transcript
isoforms. Expression of genes through splicing of pre-mRNA plays crucial roles in
cellular development, identity, and processes. Both the identity of genes selected for
transcription and the specific transcript isoforms that are expressed are essential for
normal cellular function. Deviations in gene expression or isoform proportion can be an
indication or the cause of disease.
RNA sequencing (RNAseq) is a high-throughput next-generation sequencing technology
that allows for the interrogation of gene expression on a massive scale. RNAseq
generates short sequences that reflect pieces of mRNAs present in a sample. RNAseq can
therefore be used to explore differences in gene expression, reveal transcript isoform
identities and compare changes in isoform proportions. In this dissertation, I design and
apply advanced analysis techniques to RNAseq, phenotypic and drug response data to
investigate disease mechanisms and drug sensitivity. Research Goals: The work described in this dissertation accomplishes 4 aims. Aim 1)
Evaluate the gene expression signature of concussion in collegiate athletes and identify
potential biomarkers for response and recovery. Aim 2) Implement a machine-learning
algorithm to determine if splicing can predict drug response in cancer cell lines. Aim 3)
Design a fast, scalable method to identify differentially spliced events related to cancer
drug response. Aim 4) Construct a drug-splicing network and use a systems biology
approach to search for similarities in underlying splicing events.
| Identifer | oai:union.ndltd.org:IUPUI/oai:scholarworks.iupui.edu:1805/27735 |
| Date | 01 1900 |
| Creators | Simpson, Edward Ronald Jr. |
| Contributors | Liu, Yunlong, Janga, Sarath, Wan, Jun, Wu, Huanmei, Yan, Jingwen |
| Source Sets | Indiana University-Purdue University Indianapolis |
| Language | en_US |
| Detected Language | English |
| Type | Dissertation |
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