Physical Sciences and Mathematics Commons^™

Towards Personalized Medicine: Computational Approaches For Drug Repurposing And Cell Type Identification, Azam Peyvandipour

Wayne State University Dissertations

The traditional drug discovery process is extremely slow and costly. More than 90% of drugs fail to pass beyond the early stage of development and toxicity tests, and many of the drugs that go through early phases of the clinical trials fail because of adverse reactions, side effects, or lack of efficiency. In spite of unprecedented investments in research and development (R&D), the number of new FDA-approved drugs remains low, reflecting the limitations of the current R&D model.

In this context, finding new disease indications for existing drugs sidesteps these issues and can therefore increase the available therapeutic choices at …

Integrative Pathway Analysis Pipeline For Mirna And Mrna Data, Diana Mabel Diaz Herrera

Wayne State University Theses

The identification of pathways that are involved in a particular phenotype helps us understand the underlying biological processes. Traditional pathway analysis techniques aim to infer the impact on individual pathways using only mRNA levels. However, recent studies showed that gene expression alone is unable to capture the whole picture of biological phenomena. At the same time, MicroRNAs (miRNAs) are newly discovered gene regulators that have shown to play an important role in diagnosis, and prognosis for different types of diseases. Current pathway analysis techniques do not take miRNAs into consideration. In this project, we investigate the effect of integrating miRNA …

Algorithms And Tools For Computational Analysis Of Human Transcriptome Using Rna-Seq, Nan Deng

Wayne State University Dissertations

Alternative splicing plays a key role in regulating gene expression, and more than 90% of human genes are alternatively spliced through different types of alternative splicing. Dysregulated alternative splicing events have been linked to a number of human diseases. Recently, high-throughput RNA-Seq technologies have provided unprecedented opportunities to better characterize and understand transcriptomes, in particular useful for the detection of splicing variants between healthy and diseased human transcriptomes.

We have developed two novel algorithms and tools and a computational workflow to interrogate human transcriptomes between healthy and diseased conditions. The first is a read count-based Expectation-Maximization (EM) algorithm and tool, …

The Rna Newton Polytope And Learnability Of Energy Parameters, Elmirasadat Forouzmand

Wayne State University Theses

Computational RNA secondary structure prediction has been a topic of much research interest for several decades now. Despite all the progress made in the field, even the state-of-the-art algorithms do not provide satisfying results, and the accuracy of output is limited for all the existent tools. Very complex energy models, different parameter estimation methods, and recent machine learning approaches had not been the answer for this problem. We believe that the first step to achieve results with high quality is to use the energy model with the potential for predicting accurate output. Hence, it is necessary to have a systematic …

Disulfide By Design 2.0: A Web-Based Tool For Disulfide Engineering In Proteins, Douglas B. Craig, Alan A. Dombkowski

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Disulfide engineering is an important biotechnological tool that has advanced a wide range of research. The introduction of novel disulfide bonds into proteins has been used extensively to improve protein stability, modify functional characteristics, and to assist in the study of protein dynamics. Successful use of this technology is greatly enhanced by software that can predict pairs of residues that will likely form a disulfide bond if mutated to cysteines.

Results

We had previously developed and distributed software for this purpose: Disulfide by Design (DbD). The original DbD program has been widely used; however, it has a number …