Bioinformatics Commons^™

Molecular Understanding And Design Of Deep Eutectic Solvents And Proteins Using Computer Simulations And Machine Learning, Usman Lame Abbas

Theses and Dissertations--Chemical and Materials Engineering

Hydrophobic deep eutectic solvents (DESs) have emerged as excellent extractants. A major challenge is the lack of an efficient tool to discover DES candidates. Currently, the search relies heavily on the researchers’ intuition or a trial-and-error process, which leads to a low success rate or bypassing of promising candidates. DES performance depends on the heterogeneous hydrogen bond environment formed by multiple hydrogen bond donors and acceptors. Understanding this heterogeneous hydrogen bond environment can help develop principles for designing high performance DESs for extraction and other separation applications. This work investigates the structure and dynamics of hydrogen bonds in hydrophobic DESs …

Wearable Sensor Gait Analysis For Fall Detection Using Deep Learning Methods, Haben Girmay Yhdego

Electrical & Computer Engineering Theses & Dissertations

World Health Organization (WHO) data show that around 684,000 people die from falls yearly, making it the second-highest mortality rate after traffic accidents [1]. Early detection of falls, followed by pneumatic protection, is one of the most effective means of ensuring the safety of the elderly. In light of the recent widespread adoption of wearable sensors, it has become increasingly critical that fall detection models are developed that can effectively process large and sequential sensor signal data. Several researchers have recently developed fall detection algorithms based on wearable sensor data. However, real-time fall detection remains challenging because of the wide …

Gene Expression–Based Algorithms For The Identification Of Drug Combinations In Personalized Medicine, Lon Fong

Dissertations & Theses (Open Access)

Three of the major problems facing cancer therapeutics are 1) drug resistance, the intrinsic or acquired ability of cancer cells to evade the effect of the therapies used to treat them; 2) heterogeneity among individual patients’ disease at the molecular level and the resulting variability in therapeutic response; and 3) the limitations of genomics biomarkers in matching patients to the most effective therapy. One possible solution to drug resistance is the use of combination therapies rather than monotherapies. Use of multiple drugs, each with a different mechanism of action, lowers the chances that the cancer cells will develop or have …

Applying Data Science And Machine Learning To Understand Health Care Transition For Adolescents And Emerging Adults With Special Health Care Needs, Lisamarie Turk

Nursing ETDs

A problem of classification places adolescents and emerging adults with special health care needs among the most at risk for poor or life-threatening health outcomes. This preliminary proof-of-concept study was conducted to determine if phenotypes of health care transition (HCT) for this vulnerable population could be established. Such phenotypes could support development of future studies that require data classifications as input. Mining of electronic health record data and cluster analysis were implemented to identify phenotypes. Subsequently, a machine learning concept model was developed for predicting acute care and medical condition severity. Three clusters were identified and described (Cluster 1, n …

Improved Computational Prediction Of Function And Structural Representation Of Self-Cleaving Ribozymes With Enhanced Parameter Selection And Library Design, James D. Beck

Boise State University Theses and Dissertations

Biomolecules could be engineered to solve many societal challenges, including disease diagnosis and treatment, environmental sustainability, and food security. However, our limited understanding of how mutational variants alter molecular structures and functional performance has constrained the potential of important technological advances, such as high-throughput sequencing and gene editing. Ribonuleic Acid (RNA) sequences are thought to play a central role within many of these challenges. Their continual discovery throughout all domains of life is evidence of their significant biological importance (Weinreb et al., 2016). The self-cleaving ribozyme is a class of noncoding Ribonuleic Acid (ncRNA) that has been useful for …

Machine Learning Models For Human Synapse Genomics, Anqi Wei

All Dissertations

In the central nervous system, synapses are essential junctions that connect neurons and play important roles in neurotransmission and synaptic plasticity. While there are many challenges in human synapse genomics, machine learning techniques, which are capable of mining and interpreting large amounts of genomic data, may be utilized to facilitate the functional studies of human synapses. In this study, we have developed machine learning models for human synapse genomics to address several biological problems.

RNA localization plays an important role at the synapse, allowing local protein synthesis required for synaptic plasticity during brain development. Previous studies were conducted in mice …

What I Talk About When I Talk About Integration Of Single-Cell Data, Yang Xu

Doctoral Dissertations

Over the past decade, single-cell technologies evolved from profiling hundreds of cells to millions of cells, and emerged from a single modality of data to cover multiple views at single-cell resolution, including genome, epigenome, transcriptome, and so on. With advance of these single-cell technologies, the booming of multimodal single-cell data creates a valuable resource for us to understand cellular heterogeneity and molecular mechanism at a comprehensive level. However, the large-scale multimodal single-cell data also presents a huge computational challenge for insightful integrative analysis. Here, I will lay out problems in data integration that single-cell research community is interested in and …

Framework For The Evaluation Of Perturbations In The Systems Biology Landscape And Inter-Sample Similarity From Transcriptomic Datasets — A Digital Twin Perspective, Mariah Marie Hoffman

Dissertations and Theses

One approach to interrogating the complexities of human systems in their well-regulated and dysregulated states is through the use of digital twins. Digital twins are virtual representations of physical systems that are descriptive of an individual's state of health, an object fundamentally related to precision medicine. A key element for building a functional digital twin type for a disease or predicting the therapeutic efficacy of a potential treatment is harmonized, machine-parsable domain knowledge. Hypothesis-driven investigations are the gold standard for representing subsystems, but their results encompass a limited knowledge of the full biosystem. Multi-omics data is one rich source of …

Intelligent Resource Prediction For Hpc And Scientific Workflows, Benjamin Shealy

All Dissertations

Scientific workflows and high-performance computing (HPC) platforms are critically important to modern scientific research. In order to perform scientific experiments at scale, domain scientists must have knowledge and expertise in software and hardware systems that are highly complex and rapidly evolving. While computational expertise will be essential for domain scientists going forward, any tools or practices that reduce this burden for domain scientists will greatly increase the rate of scientific discoveries. One challenge that exists for domain scientists today is knowing the resource usage patterns of an application for the purpose of resource provisioning. A tool that accurately estimates these …

Deep Learning Applications In Medical Bioinformatics, Ziad Omar

Electronic Theses and Dissertations

After a patient’s breast cancer diagnosis, identifying breast cancer lymph node metastases is one of the most important and critical factor that is directly related to the patient’s survival. The traditional way to examine the existence of cancer cells in the breast lymph nodes is through a lymph node procedure, biopsy. The procedure process is time-consuming for the patient and the provider, costly, and lacks accuracy as not every lymph node is examined. The intent of this study is to develop an artificial neural network (ANNs) that would map genetic biomarkers to breast lymph node classes using ANNs. The neural …

Gene Selection And Classification In High-Throughput Biological Data With Integrated Machine Learning Algorithms And Bioinformatics Approaches, Abhijeet R Patil

Open Access Theses & Dissertations

With the rise of high throughput technologies in biomedical research, large volumes of expression profiling, methylation profiling, and RNA-sequencing data are being generated. These high-dimensional data have large number of features with small number of samples, a characteristic called the "curse of dimensionality." The selection of optimal features, which largely affects the performance of classification algorithms in machine learning models, has led to challenging problems in bioinformatics analyses of such high-dimensional datasets. In this work, I focus on the design of two-stage frameworks of feature selection and classification and their applications in multiple sets of colorectal cancer data. The first …

Using Machine Learning To Predict Super-Utilizers Of Healthcare Services, Kevin Paul Buchan Jr.

Legacy Theses & Dissertations (2009 - 2024)

In this dissertation, I aim to forecast high utilizers of emergency care and inpatient Medicare services (i.e., healthcare visits). Through a literature review, I demonstrate that accurate and reliable prediction of these future high utilizers will not only reduce healthcare costs but will also improve the overall quality of healthcare for patients. By identifying this population at risk before manifestation, I propose that there is still time to reverse undesirable healthcare trajectories (i.e., individuals whose clinical risk increases an excessive healthcare and treatment burden) through timely attention and proper care coordination. My dissertation culminates in the delivery of state-of-the-art predictive …

Machine Learning And Bioinformatic Insights Into Key Enzymes For A Bio-Based Circular Economy, Japheth E. Gado

Theses and Dissertations--Chemical and Materials Engineering

The world is presently faced with a sustainability crisis; it is becoming increasingly difficult to meet the energy and material needs of a growing global population without depleting and polluting our planet. Greenhouse gases released from the continuous combustion of fossil fuels engender accelerated climate change, and plastic waste accumulates in the environment. There is need for a circular economy, where energy and materials are renewably derived from waste items, rather than by consuming limited resources. Deconstruction of the recalcitrant linkages in natural and synthetic polymers is crucial for a circular economy, as deconstructed monomers can be used to manufacture …

Applications Of Machine Learning In Microbial Forensics, Ryan B. Ghannam

Dissertations, Master's Theses and Master's Reports

Microbial ecosystems are complex, with hundreds of members interacting with each other and the environment. The intricate and hidden behaviors underlying these interactions make research questions challenging – but can be better understood through machine learning. However, most machine learning that is used in microbiome work is a black box form of investigation, where accurate predictions can be made, but the inner logic behind what is driving prediction is hidden behind nontransparent layers of complexity.

Accordingly, the goal of this dissertation is to provide an interpretable and in-depth machine learning approach to investigate microbial biogeography and to use micro-organisms as …

Ensemble Protein Inference Evaluation, Kyle Lee Lucke

Graduate Student Theses, Dissertations, & Professional Papers

The Protein inference problem is becoming an increasingly important tool that aids in the characterization of complex proteomes and analysis of complex protein samples. In bottom-up shotgun proteomics experiments the metrics for evaluation (like AUC and calibration error) are based on an often imperfect target-decoy database. These metrics make the inherent assumption that all of the proteins in the target set are present in the sample being analyzed. In general, this is not the case, they are typically a mix of present and absent proteins. To objectively evaluate inference methods, protein standard datasets are used. These datasets are special in …

Modified-Half-Normal Distribution And Different Methods To Estimate Average Treatment Effect., Jingchao Sun

Electronic Theses and Dissertations

This dissertation consists of three projects related to Modified-Half-Normal distribution and causal inference. In my first project, a new distribution called Modified-Half-Normal distribution was introduced. I explored a few of its distributional properties, the procedures for generating random samples based on Bayesian approaches, and the parameter estimation based on the method of moments. The second project deals with the problem of selection bias of average treatment effect (ATE) if we use the observational data. I combined the propensity score based inverse probability of treatment weighting (IPTW) method and the directed acyclic graph (DAG) to solve this problem. The third project …

New Methods For Deep Learning Based Real-Valued Inter-Residue Distance Prediction, Jacob Barger

Theses

Background: Much of the recent success in protein structure prediction has been a result of accurate protein contact prediction--a binary classification problem. Dozens of methods, built from various types of machine learning and deep learning algorithms, have been published over the last two decades for predicting contacts. Recently, many groups, including Google DeepMind, have demonstrated that reformulating the problem as a multi-class classification problem is a more promising direction to pursue. As an alternative approach, we recently proposed real-valued distance predictions, formulating the problem as a regression problem. The nuances of protein 3D structures make this formulation appropriate, allowing predictions …

Enrichment Of Ontologies Using Machine Learning And Summarization, Hao Liu

Dissertations

Biomedical ontologies are structured knowledge systems in biomedicine. They play a major role in enabling precise communications in support of healthcare applications, e.g., Electronic Healthcare Records (EHR) systems. Biomedical ontologies are used in many different contexts to facilitate information and knowledge management. The most widely used clinical ontology is the SNOMED CT. Placing a new concept into its proper position in an ontology is a fundamental task in its lifecycle of curation and enrichment.

A large biomedical ontology, which typically consists of many tens of thousands of concepts and relationships, can be viewed as a complex network with concepts as …

Classification Of Bacterial Motility Using Machine Learning, Yue Ma

Masters Theses

Cells can display a diverse set of motility behaviors, and these behaviors may reflect a cell’s functional state. Automated, and accurate cell motility analysis is essential to cell studies where the analysis of motility pattern is required. The results of such analysis can be used for diagnostic or curative decisions. Deep learning area has made astonishing progresses in the past several years. For computer vision tasks, different convolutional neural networks (CNN) and optimizers have been proposed to fix some problems. For time sequence data, recurrent neural networks (RNN) have been widely used.

This project leveraged on these recent advances to …

Mhcherrypan, A Novel Model To Predict The Binding Affinity Of Pan-Specific Class I Hla-Peptide, Xuezhi Xie

Electronic Thesis and Dissertation Repository

The human leukocyte antigen (HLA) system or complex plays an essential role in regulating the immune system in humans. Accurate prediction of peptide binding with HLA can efficiently help to identify those neoantigens, which potentially make a big difference in immune drug development. HLA is one of the most polymorphic genetic systems in humans, and thousands of HLA allelic versions exist. Due to the high polymorphism of HLA complex, it is still pretty difficult to accurately predict the binding affinity. In this thesis, we presented a new algorithm to combine convolutional neural network and long short-term memory to solve this …

Methods To Integrate Genetic And Clinical Data For Disease Subtyping, Diana Mabel Diaz-Herrera

Wayne State University Dissertations

Enormous efforts have been made to collect genetic and clinical data from cancer patients to advance the understanding of disease development and progression. Processing and analyzing these flows of data is challenging. Many computational methods have been proposed to help different fronts of biology and medicine. The integration of clinical and genetic data using computational methods towards personalized medicine is considered the future for oncology studies, and this thesis contributes in this direction. This thesis presents three new data integration approaches to elucidate granular and meaningful disease sub-types from high-dimensional complex genetic and clinical variables, which is an essential step …

Cancer Risk Prediction With Whole Exome Sequencing And Machine Learning, Abdulrhman Fahad M Aljouie

Dissertations

Accurate cancer risk and survival time prediction are important problems in personalized medicine, where disease diagnosis and prognosis are tuned to individuals based on their genetic material. Cancer risk prediction provides an informed decision about making regular screening that helps to detect disease at the early stage and therefore increases the probability of successful treatments. Cancer risk prediction is a challenging problem. Lifestyle, environment, family history, and genetic predisposition are some factors that influence the disease onset. Cancer risk prediction based on predisposing genetic variants has been studied extensively. Most studies have examined the predictive ability of variants in known …

Model-Based Deep Autoencoders For Characterizing Discrete Data With Application To Genomic Data Analysis, Tian Tian

Dissertations

Deep learning techniques have achieved tremendous successes in a wide range of real applications in recent years. For dimension reduction, deep neural networks (DNNs) provide a natural choice to parameterize a non-linear transforming function that maps the original high dimensional data to a lower dimensional latent space. Autoencoder is a kind of DNNs used to learn efficient feature representation in an unsupervised manner. Deep autoencoder has been widely explored and applied to analysis of continuous data, while it is understudied for characterizing discrete data. This dissertation focuses on developing model-based deep autoencoders for modeling discrete data. A motivating example of …

Highly Accurate Fragment Library For Protein Fold Recognition, Wessam Elhefnawy

Computer Science Theses & Dissertations

Proteins play a crucial role in living organisms as they perform many vital tasks in every living cell. Knowledge of protein folding has a deep impact on understanding the heterogeneity and molecular functions of proteins. Such information leads to crucial advances in drug design and disease understanding. Fold recognition is a key step in the protein structure discovery process, especially when traditional computational methods fail to yield convincing structural homologies. In this work, we present a new protein fold recognition approach using machine learning and data mining methodologies.

First, we identify a protein structural fragment library (Frag-K) composed of a …

Applying Machine Learning Algorithms For The Analysis Of Biological Sequences And Medical Records, Shaopeng Gu

Electronic Theses and Dissertations

The modern sequencing technology revolutionizes the genomic research and triggers explosive growth of DNA, RNA, and protein sequences. How to infer the structure and function from biological sequences is a fundamentally important task in genomics and proteomics fields. With the development of statistical and machine learning methods, an integrated and user-friendly tool containing the state-of-the-art data mining methods are needed. Here, we propose SeqFea-Learn, a comprehensive Python pipeline that integrating multiple steps: feature extraction, dimensionality reduction, feature selection, predicting model constructions based on machine learning and deep learning approaches to analyze sequences. We used enhancers, RNA N6- methyladenosine sites and …

Dna Sequence Classification: It’S Easier Than You Think: An Open-Source K-Mer Based Machine Learning Tool For Fast And Accurate Classification Of A Variety Of Genomic Datasets, Stephen Solis-Reyes

Electronic Thesis and Dissertation Repository

Supervised classification of genomic sequences is a challenging, well-studied problem with a variety of important applications. We propose an open-source, supervised, alignment-free, highly general method for sequence classification that operates on k-mer proportions of DNA sequences. This method was implemented in a fully standalone general-purpose software package called Kameris, publicly available under a permissive open-source license. Compared to competing software, ours provides key advantages in terms of data security and privacy, transparency, and reproducibility. We perform a detailed study of its accuracy and performance on a wide variety of classification tasks, including virus subtyping, taxonomic classification, and human haplogroup assignment. …

Prediction Of 1p/19q Codeletion Status In Diffuse Glioma Patients Using Preoperative Multiparametric Magnetic Resonance Imaging, Donnie Kim

Dissertations & Theses (Open Access)

A complete codeletion of chromosome 1p/19q is strongly correlated with better overall survival of diffuse glioma patients, hence determining the codeletion status early in the course of a patient’s disease would be valuable in that patient’s care. The current practice requires a surgical biopsy in order to assess the codeletion status, which exposes patients to risks and is limited in its accuracy by sampling variations. To overcome such limitations, we utilized four conventional magnetic resonance imaging sequences to predict the 1p/19q status. We extracted three sets of image-derived features, namely texture-based, topology-based, and convolutional neural network (CNN)-based, and analyzed each …

Discerning Drivers Of Cancer: Computational Approaches To Somatic Exome Sequencing Data, Runjun Kumar

Arts & Sciences Electronic Theses and Dissertations

Paired tumor-normal sequencing of thousands of patient’s exomes has revealed millions of somatic mutations, but functional characterization and clinical decision making are stymied because biologically neutral ‘passenger’ mutations greatly outnumber pathogenic ‘driver’ mutations. Since most mutations will return negative results if tested, conventional resource-intensive experiments are reserved for mutations which are observed in multiple patients or rarer mutations found in well-established cancer genes. Most mutations are therefore never tested, diminishing the potential to discover new mechanisms of cancer development and treatment opportunities. Computational methods that reliably prioritize mutations for testing would greatly increase the translation of sequencing results to clinical …

Clinical Information Extraction From Unstructured Free-Texts, Mingzhe Tao

Legacy Theses & Dissertations (2009 - 2024)

Information extraction (IE) is a fundamental component of natural language processing (NLP) that provides a deeper understanding of the texts. In the clinical domain, documents prepared by medical experts (e.g., discharge summaries, drug labels, medical history records) contain a significant amount of clinically-relevant information that is crucial to the overall well-being of patients. Unfortunately, in many cases, clinically-relevant information is presented in an unstructured format, predominantly consisting of free-texts, making it inaccessible to computerized methods. Automatic extraction of this information can improve accessibility. However, the presence of synonymous expressions, medical acronyms, misspellings, negated phrases, and ambiguous terminologies make automatic extraction …

Understanding Huntington's Disease Using Machine Learning Approaches, Sonali Lokhande

KGI Theses and Dissertations

Huntington’s disease (HD) is a debilitating neurodegenerative disorder with a complex pathophysiology. Despite extensive studies to study the disease, the sequence of events through which mutant Huntingtin (mHtt) protein executes its action still remains elusive. The phenotype of HD is an outcome of numerous processes initiated by the mHtt protein along with other proteins that act as either suppressors or enhancers of the effects of mHtt protein and PolyQ aggregates. Utilizing an integrative systems biology approach, I construct and analyze a Huntington’s disease integrome using human orthologs of protein interactors of wild type and mHtt protein. Analysis of this integrome …