Indiana University-Purdue University Indianapolis (IUPUI) / The rapid innovations in biotechnology have led to an exponential growth of data
and electronically accessible scientific literature. In this enormous scientific data,
knowledge can be exploited, and novel discoveries can be made. In my dissertation, I
have focused on the novel molecular mechanism and therapeutic discoveries from big
data for complex diseases. It is very evident today that complex diseases have many
factors including genetics and environmental effects. The discovery of these factors is
challenging and critical in personalized medicine. The increasing cost and time to
develop new drugs poses a new challenge in effectively treating complex diseases. In this
dissertation, we want to demonstrate that the use of existing data and literature as a
potential resource for discovering novel therapies and in repositioning existing drugs. The
key to identifying novel knowledge is in integrating information from decades of research
across the different scientific disciplines to uncover interactions that are not explicitly
stated. This puts critical information at the fingertips of researchers and clinicians who
can take advantage of this newly acquired knowledge to make informed decisions.
This dissertation utilizes computational biology methods to identify and integrate
existing scientific data and literature resources in the discovery of novel molecular targets
and drugs that can be repurposed. In chapters 1 of my dissertation, I extensively sifted
through scientific literature and identified a novel interaction between Vitamin A and CYP19A1 that could lead to a potential increase in the production of estrogens. Further in
chapter 2 by exploring a microarray dataset from an estradiol gene sensitivity study I was
able to identify a potential novel anti-estrogenic indication for the commonly used
urinary analgesic, phenazopyridine. Both discoveries were experimentally validated in
the laboratory. In chapter 3 of my dissertation, through the use of a manually curated
corpus and machine learning algorithms, I identified and extracted genes that are
essential for cell survival. These results brighten the reality that novel knowledge with
potential clinical applications can be discovered from existing data and literature by
integrating information across various scientific disciplines.
| Identifer | oai:union.ndltd.org:IUPUI/oai:scholarworks.iupui.edu:1805/10978 |
| Date | 20 June 2016 |
| Creators | Philips, Santosh |
| Contributors | Li, Lang, Liu, Yunlong, Liu, Xiaowen, Skaar, Todd C., Janga, Sarath C. |
| Source Sets | Indiana University-Purdue University Indianapolis |
| Language | en_US |
| Detected Language | English |
| Type | Dissertation |
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