Bioinformatics Commons^™

Genetic Predictors Of Metabolic Side Effects Of Diuretic Therapy, Jorge L. Del Aguila

Dissertations & Theses (Open Access)

Thiazide diuretics are a recommended first-line monotherapy for hypertension (i.e.SBP>140 mmHg or DBP>90 mmHg). Even so, diuretics are associated with adverse metabolic side effects, such as hyperlipidemia, hyperglycemia and hypokalemia which increase the risk of developing type II diabetes. This thesis used three analytical strategies to identify and quantify genetic factors that contribute to the development of adverse metabolic effects due to thiazide diuretic treatment. I performed a genome-wide association study (GWAS) and meta-analysis of the change in fasting plasma glucose and triglycerides in response to HCTZ from two different clinical trials: the Pharmacogenomic Evaluation of Antihypertensive Responses …

Improvements On Segment Based Contours Method For Dna Microarray Image Segmentation, Yang Li

Doctoral Dissertations

DNA microarray is an efficient biotechnology tool for scientists to measure the expression levels of large numbers of genes, simultaneously. To obtain the gene expression, microarray image analysis needs to be conducted. Microarray image segmentation is a fundamental step in the microarray analysis process. Segmentation gives the intensities of each probe spot in the array image, and those intensities are used to calculate the gene expression in subsequent analysis procedures. Therefore, more accurate and efficient microarray image segmentation methods are being pursued all the time.

In this dissertation, we are making efforts to obtain more accurate image segmentation results. We …

Improving Structural Features Prediction In Protein Structure Modeling, Ashraf Yaseen

Computer Science Theses & Dissertations

Proteins play a vital role in the biological activities of all living species. In nature, a protein folds into a specific and energetically favorable three-dimensional structure which is critical to its biological function. Hence, there has been a great effort by researchers in both experimentally determining and computationally predicting the structures of proteins.

The current experimental methods of protein structure determination are complicated, time-consuming, and expensive. On the other hand, the sequencing of proteins is fast, simple, and relatively less expensive. Thus, the gap between the number of known sequences and the determined structures is growing, and is expected to …

Risk Prediction With Genomic Data, Bharati Jadhav

Theses

Genome wide association study (GWAS) is widely used with various machine learning algorithms to predict disease risk. This thesis investigates this widely used approach of GWAS using Single Nucleotide Polymorphism (SNP) genotype data and a novel approach of disease risk prediction with whole exome sequencing data, namely Whole Exome Wide Association Study (WEWAS). It further applies a discriminating machine learning algorithm, namely a Support Vector Machine (SVM) with different Kernel functions. For this study, only SNPs generated using genotyping technology, which focuses more on common variants, are used initially for disease prediction. Later, the whole exome data generated using Next …

Disease Name Extraction From Clinical Text Using Conditional Random Fields, Omid Ghiasvand

Theses and Dissertations

The aim of the research done in this thesis was to extract disease and disorder names from clinical texts. We utilized Conditional Random Fields (CRF) as the main method to label diseases and disorders in clinical sentences. We used some other tools such as MetaMap and Stanford Core NLP tool to extract some crucial features. MetaMap tool was used to identify names of diseases/disorders that are already in UMLS Metathesaurus. Some other important features such as lemmatized versions of words, and POS tags were extracted using the Stanford Core NLP tool. Some more features were extracted directly from UMLS Metathesaurus, …

The Association Between The Il-1 Pathway, Isaac C. Wun

Dissertations & Theses (Open Access)

Cutaneous malignant melanoma (CMM) is a potentially lethal malignancy that warrants attention and further research, as it is known to that there is an increasing rate of incidence in theUnited States, and it is also known that exposure to UV light is its most crucial risk factor, and family history of melanoma is also an important risk factor. Melanoma is an aggressive and lethal cancer in humans. There are an estimated new 132,000 melanoma cases annually worldwide, and the trend has doubled in the past 20 years. However, attempts to treat melanoma have encountered considerable resistance and remained ineffective. The …

Statistical Methods For Assessing Treatment Effects For Observational Studies., Kristopher C. Gardner 1984-

Electronic Theses and Dissertations

Though randomized clinical (RCTs) trials are the gold standard for comparing treatments, they are often infeasible or exclude clinically important subjects, or generally represent an idealized medical setting rather than real practice. Observational data provide an opportunity to study practice-based evidence, but also present challenges for analysis. Traditional statistical methods which are suitable for RCTs may be inadequate for the observational studies. In this project, four of the most popular statistical methods for observational studies: ANCOVA, propensity score matching, regression with the propensity score as a covariate, and instrumental variables (IV) are investigated through application to MarketScan insurance claims data. …

Stream Crossing Barrier Prioritization Methods For Increasing Eastern Brook Trout Habitat In The Little Androscoggin River Watershed, Michele Windsor

Thinking Matters Symposium Archive

Eastern Brook Trout (Salvelinas fontanalis) are an important cold water fishery in the state of Maine. While populations in Maine are relatively abundant there has been decline in some parts of its range due in part to loss of habitat connectivity. Brook trout require access to specific types of stream habitat for spawning, feeding, and seasonal thermal refuges. Stream crossing structures such as undersized, poorly installed, or blocked culverts, as well as small remnant dams, can create barriers to accessing important stream habitat for brook trout. A recent Fish Barrier/Culvert Survey in the Little Androscoggin River Watershed provided data about …

Modeling Stem Cell Population Dynamics, Samiur Arif

Computer Science Theses & Dissertations

Because of the stochastic nature of biological systems, mathematical and computational modeling approaches have become more acceptable to experimentalists and clinicians in recent years as contributing to new understandings of complicated cell mechanisms and tissue physiology. Indeed, even single cell or small tissue samples are complex dynamic systems that adapt to environmental challenges in space and time which is poorly understood. Mathematical models and computer simulations can explain and uncover unknown aspects of cell behavior and tissue functions. Models based on key biological mechanisms can give interesting insights and formulate predictions that cannot be derived from physical experiments or statistical …

Identification Of Transcriptionally Quiescent Regions In The Neurospora Crassa Genome, Katie Marie Groskreutz

Theses and Dissertations

Sexual reproduction and genetic exchange via meiosis are important and highly conserved processes in many living organisms. Occasionally, complications occur during meiosis that can result in chromosome abnormalities. In humans, improper chromosome development can cause life altering disorders such as Down Syndrome, Edwards Syndrome, and Patau Syndrome. Unfortunately, despite its importance, gaps remain in our knowledge of how this process works. For instance, little is known about how homolog identification occurs and what proteins identify matching chromosomes during pairing. This fundamental process occurs early during meiosis and ensures proper development of gametes.

Understanding the proteins involved during homolog pairing may …

Analysis Of Dna Motifs In The Human Genome, Yupu Liang

Dissertations, Theses, and Capstone Projects

DNA motifs include repeat elements, promoter elements and gene regulator elements, and play a critical role in the human genome. This thesis describes a genome-wide computational study on two groups of motifs: tandem repeats and core promoter elements.

Tandem repeats in DNA sequences are extremely relevant in biological phenomena and diagnostic tools. Computational programs that discover tandem repeats generate a huge volume of data, which can be difficult to decipher without further organization. A new method is presented here to organize and rank detected tandem repeats through clustering and classification. Our work presents multiple ways of expressing tandem repeats using …

Comparison Of Different Differential Expression Analysis Tools For Rna-Seq Data, Junfei Zhu

Theses

In molecular biology research, RNA-seq is a relatively new method for transcriptome profiling. It utilizes the next generation sequencing technology to provide huge amount information about the variety and abundance of RNA present in an organism of interest at a specific state and a given time. One of the most important tasks of RNA-seq analysis is finding genes that are expressed differently in different subject groups. A lot of differential expression analysis tools for RNA-seq have been developed, but there is no golden standard in this field. In this research, four commonly used tools (DESeq, edgeR, limma, and cuffdiff) are …

Oligonucleotide Design For Whole Genome Tiling Arrays, Qin Dong

Electronic Thesis and Dissertation Repository

Oligonucleotides are short, single-stranded fragments of DNA or RNA, designed to readily bind with a unique part in the target sequence. They have many important applications including PCR (polymerase chain reaction) amplification, microarrays, or FISH (fluorescence in situ hybridization) probes. While traditional microarrays are commonly used for measuring gene expression levels by probing for sequences of known and predicted genes, high-density, whole genome tiling arrays probe intensively for sequences that are known to exist in a contiguous region. Current programs for designing oligonucleotides for tiling arrays are not able to produce results that are close to optimal since they allow …

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 …

De Novo Co-Assembly Of Bacterial Genomes From Multiple Single Cells, Narjes Sadat Movahedi Tabrizi

Wayne State University Theses

Recent progress in DNA amplication techniques, particularly multiple displacement amplication (MDA), has made it possible to sequence and assemble bacterial genomes from a single cell. However, the quality of single cell genome assembly has not yet reached the quality of normal multicell genome assembly due to the coverage bias and errors caused by MDA. Using a template of more than one cell for MDA or combining separate MDA products has been shown to improve the result of genome assembly from few single cells, but providing identical single cells, as a necessary step for these approaches, is a challenge. As a …

Methods For Integrative Analysis Of Genomic Data, Paul Manser

Theses and Dissertations

In recent years, the development of new genomic technologies has allowed for the investigation of many regulatory epigenetic marks besides expression levels, on a genome-wide scale. As the price for these technologies continues to decrease, study sizes will not only increase, but several different assays are beginning to be used for the same samples. It is therefore desirable to develop statistical methods to integrate multiple data types that can handle the increased computational burden of incorporating large data sets. Furthermore, it is important to develop sound quality control and normalization methods as technical errors can compound when integrating multiple genomic …

Teak: A Novel Computational And Gui Software Pipeline For Reconstructing Biological Networks, Detecting Activated Biological Subnetworks, And Querying Biological Networks., Thair Judeh

Wayne State University Dissertations

As high-throughput gene expression data becomes cheaper and cheaper, researchers are faced with a deluge of data from which biological insights need to be extracted and mined since the rate of data accumulation far exceeds the rate of data analysis. There is a need for computational frameworks to bridge the gap and assist researchers in their tasks. The Topology Enrichment Analysis frameworK (TEAK) is an open source GUI and software pipeline that seeks to be one of many tools that fills in this gap and consists of three major modules. The first module, the Gene Set Cultural Algorithm, de novo …

Natural Phenomena As Potential Influence On Social And Political Behavior: The Earth’S Magnetic Field, Jackie R. East

Theses and Dissertations--Political Science

Researchers use natural phenomena in a number of disciplines to help explain human behavioral outcomes. Research regarding the potential effects of magnetic fields on animal and human behavior indicates that fields could influence outcomes of interest to social scientists. Tests so far have been limited in scope. This work is a preliminary evaluation of whether the earth’s magnetic field influences human behavior it examines the baseline relationship exhibited between geomagnetic readings and a host of social and political outcomes. The emphasis on breadth of topical coverage in these statistical trials, rather than on depth of development for any one model, …

Time Will Tell : Temporal Reasoning In Clinical Narratives And Beyond, Weiyi Sun

Legacy Theses & Dissertations (2009 - 2024)

Temporal reasoning in natural language refers to the extraction and understanding of time-related information conveyed in free text. A clinical narrative temporal reasoning component can enable a spectrum of medical natural language processing (NLP) applications that directly improve patient care documentation efficiency, accessibility and accountability. This dissertation contributes in three subtasks under temporal reasoning: temporal annotation, temporal expression extraction and temporal relation inferences. The temporal annotation work described in the dissertation produced one of the first publicly available clinical narratives. We published one of the first sets of temporal