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Articles 1 - 14 of 14
Full-Text Articles in Bioinformatics
Identification Of Candidate Microbial Biomarkers Of Disease And Design Of Engineered Microbial Therapeutics For The Gut Microbiome, Aura Lucia Ferreiro
Identification Of Candidate Microbial Biomarkers Of Disease And Design Of Engineered Microbial Therapeutics For The Gut Microbiome, Aura Lucia Ferreiro
McKelvey School of Engineering Theses & Dissertations
The human gut microbiome is a compositionally and functionally diverse community of microorganisms that profoundly influences the health of the host. Deep characterization of gut microbiomes via high-throughput sequencing has identified associations between the gut microbiome and disease states, and spurred development of engineered microbial therapeutics. Successful translation of these research efforts to the clinic will involve i) consideration of how engineered microbes behave and adapt in the gut, towards the implementation of biosafety mechanisms, and ii) identification and validation of microbial biomarkers of disease. This dissertation describes both investigative (Chapter 2) and engineering (Chapters 3 and 4) approaches to …
On The Challenges And Rewards Of Analyzing Molecular Dynamics At The Terabyte And Millisecond Scale, Justin Roy Porter
On The Challenges And Rewards Of Analyzing Molecular Dynamics At The Terabyte And Millisecond Scale, Justin Roy Porter
Arts & Sciences Electronic Theses and Dissertations
Molecular Dynamics (MD) and Markov state models (MSMs) are powerful tools for estimating and concisely representing the conformational ensemble accessible to biological macromolecules, particularly proteins. Conformational ensembles are of special importance biological function, both in health and disease, because biology derives from molecules’ entire conformational distribution rather than any single structure. Consequently, MD is poised to become a powerful tool for personalized medicine and for the study of molecular sequence-function relationships generally. However, because of their hyperdimensionality and size, just generating MD datasets and Markov state models (MSMs) that represent biologically relevant molecules is a substantive technical challenge. Then, even …
Surveillance And Dynamics Of Bacteria And Resistance Genes In Humans And Hospitals, Alaric Wences D'Souza
Surveillance And Dynamics Of Bacteria And Resistance Genes In Humans And Hospitals, Alaric Wences D'Souza
Arts & Sciences Electronic Theses and Dissertations
Bacteria live in, on, and around us. These bacteria affect human health through beneficial commensal interactions that promote normal development and through harmful infections or perturbations leading to disease. Understanding the prevalence, spread, and resilience of these bacteria in humans and human environments is critical to clinical medicine and epidemiology. I investigated environmental and human resident bacteria to understand dynamics in bacterial communities and how these dynamics may impact human health.Hospitals are one critical location of human-bacterial interactions. Bacteria can contaminate hospital surfaces from patients or environmental sources and subsequently transmit from surfaces to vulnerable patients. I analyzed bacteria from …
Association Of Structural Variation (Sv) With Cardiometabolic Traits In Finns, Lei Chen
Association Of Structural Variation (Sv) With Cardiometabolic Traits In Finns, Lei Chen
Arts & Sciences Electronic Theses and Dissertations
Cardiovascular diseases (CVDs) are known to be associated with a variety of quantitative risk factors such as cholesterol, metabolites, and insulin. Understanding the genetic basis of these quantitative traits can shed light on the etiology, prevention, diagnosis, and treatment of disease. However most prior trait-mapping studies have focused on single nucleotide variants (SNVs) and Indels, with the contribution of structural variation (SV) remaining unknown. In this thesis, we present the results of a study examining genetic association between SVs and cardiometabolic traits in the Finnish population. In the first chapter, we used sensitive methods to identify and genotype 129,166 high-confidence …
Regulation Of Transcription Factor Binding Specificity: From Binding Motifs To Local Dna Context, Jiayue Liu
Regulation Of Transcription Factor Binding Specificity: From Binding Motifs To Local Dna Context, Jiayue Liu
Arts & Sciences Electronic Theses and Dissertations
Regulation of transcription factor (TF) binding specificity lies at the heart of transcriptional control which governs how cells divide, differentiate, and respond to their environments. TFs are known to bind to DNA in a sequence specific manner, and such short sequence is known as transcription factor binding site (TFBS). However, the in vivo TF bound regions do not always contain a TFBS, and additionally, there are often excessive non-functional TFBSs with binding potential in the regulatory regions that are unbound for a given TF. This dissertation focuses on understanding the principles of TF binding specificity and is divided into two …
Disentangling Glial Diversity In Peripheral Nerves At Single Nuclei Resolution, Aldrin Kay Yuen Yim
Disentangling Glial Diversity In Peripheral Nerves At Single Nuclei Resolution, Aldrin Kay Yuen Yim
Arts & Sciences Electronic Theses and Dissertations
The ability to discern gene expression at single cell level is revolutionizing our understanding of both basic biology and human health. Peripheral nerves are essential communicators between the outside world and the CNS, as evidenced by the devastating effects of diseases that disrupt them, such as ALS, Charcot-Marie-Tooth Syndrome and diabetic neuropathy. Understanding peripheral nerve dysfunction at a mechanistic level is of considerable interest due to the increasing prevalence and associated patient care costs of these disorders. Although most research of the peripheral nerve has focused on glial-axonal interactions, the important contributions of other cell types besides Schwann cells, such …
Analysis Of Structural Variation And Mtdna Copy Number In Finns, Liron Ganel
Analysis Of Structural Variation And Mtdna Copy Number In Finns, Liron Ganel
Arts & Sciences Electronic Theses and Dissertations
Cardiovascular disease (CVD) is a complex disease responsible for more deaths worldwide than any other cause according to the World Health Organization. Genetic association studies for CVD and related risk factors have successfully identified hundreds of loci associated with these complex diseases and traits, although much of their heritability remains unexplained. Structural variants (SVs) - including insertions, deletions, duplications, and inversions - are an understudied class of genomic variation that have the potential to explain much of the missing heritability of CVD and other complex traits. Here, we discuss advances emerging from the study of SVs in the context of …
Understanding Immune Responses With Single-Cell Rna Sequencing And Cytof Across Different Diseases And Model Organisms, Ekaterina Esaulova
Understanding Immune Responses With Single-Cell Rna Sequencing And Cytof Across Different Diseases And Model Organisms, Ekaterina Esaulova
Arts & Sciences Electronic Theses and Dissertations
The immune system is an integral part of a healthy functioning organism. Immune responses during the disease are complex and include the interplay of many cell subsets. Integrated genomics and bioinformatics usage can yield unique insights into the immune system’s function in health and disease at a single-cell resolution. Here we utilize complimentary single-cell profiling technologies, scRNA-seq and CyTOF, to explore immune responses across diseases and model organisms. Our approach included leveraging scRNA-seq on few samples to understand the immune response landscape and select key markers for a follow-up protein level validation using an appropriate number of replicates by FACS …
Comprehensive Characterization Of The Genetic And Neoantigen Landscapes Of Follicular Lymphoma Patients Supports The Feasibility Of Personalized Cancer Vaccine Treatments, Cody Alexander Ramirez
Comprehensive Characterization Of The Genetic And Neoantigen Landscapes Of Follicular Lymphoma Patients Supports The Feasibility Of Personalized Cancer Vaccine Treatments, Cody Alexander Ramirez
Arts & Sciences Electronic Theses and Dissertations
Follicular lymphoma (FL) is the most common indolent non-Hodgkin’s lymphoma; however, it remains incurable with conventional therapies and is poorly responsive to checkpoint blockade. FL arises from B-lymphocytes and develops slowly (and often asymptomatically). A major research focus has been on how to avoid chemotherapy treatments, to limit the potential development of treatment-related side effects, and the risk of therapy-related second cancers. FL also carries an approximately 30% lifetime risk of transforming from an iNHL to more destructive lymphomas, which are associated with poorer prognosis. The most common transformation results in diffuse large B-cell lymphoma (DLBCL). However, many patients may …
Mapping Transcription Factor Networks And Elucidating Their Biological Determinants, Yiming Kang
Mapping Transcription Factor Networks And Elucidating Their Biological Determinants, Yiming Kang
McKelvey School of Engineering Theses & Dissertations
A central goal in systems biology is to accurately map the transcription factor (TF) network of a cell. Such a network map is a key component for many downstream applications, from developmental biology to transcriptome engineering, and from disease modeling to drug discovery. Building a reliable network map requires a wide range of data sources including TF binding locations and gene expression data after direct TF perturbations. However, we are facing two roadblocks. First, rich resources are available only for a few well-studied systems and cannot be easily replicated for new organisms or cell types. Second, when TF binding and …
Identify Genetic And Epigenetic Abnormalities Associated With Therapeutic Vulnerability In Human Cancers, Wen-Wei Liang
Identify Genetic And Epigenetic Abnormalities Associated With Therapeutic Vulnerability In Human Cancers, Wen-Wei Liang
Arts & Sciences Electronic Theses and Dissertations
Human cancer is a complex and dynamic disease with mutational, spatial, and temporal heterogeneity. There has been a concerted effort to address the heterogeneity by profiling large-scale multiomic datasets with an emphasis on abnormalities such as DNA mutations at coding regions and structural variants. However, a systematic analysis of alterations at “dark matter” is lacking – including DNA slippage events at microsatellite sequences, gene fusions arising from genomic rearrangements, and aberrant DNA methylations at promoter regions. This dissertation focus on developing data-driven computational analysis pipelines to study the patterns of microsatellite instability, gene fusions, and aberrant DNA methylation, and their …
Differentiating Human Embryonic Stem Cells In Micropatterns To Study Cell Fate Specification And Morphogenetic Events During Gastrulation, Kyaw Thu Minn
McKelvey School of Engineering Theses & Dissertations
During mammalian embryogenesis, the first major lineage segregation occurs when embryonic epiblast, and extraembryonic trophectoderm and hypoblast arise in the blastocyst. In the next fundamental and conserved phase of animal embryogenesis known as gastrulation, extraembryonic cells provide signals to epiblast to instruct embryonic patterning, and epiblast gives rise to germ layers ectoderm, mesoderm, and endoderm, that will establish all embryonic tissues. Proper specification and morphogenesis of germ layers during gastrulation is vital for correct embryonic development. Due to ethical and legal restrictions limiting human embryo studies, human gastrulation is poorly understood. Our knowledge of human gastrulation has largely been derived …
Computational Analysis Of Non-Cpg Dna Methylation In The Mammalian Nervous System, Dennis Yawen Wu
Computational Analysis Of Non-Cpg Dna Methylation In The Mammalian Nervous System, Dennis Yawen Wu
Arts & Sciences Electronic Theses and Dissertations
Noncanonical forms of DNA methylation, especially non-CpG DNA methylation, play essential roles in the neuronal epigenome, and have only recently begun to be characterized. While most DNA methylation within mammals is found in a CG context and maintained by DNMT1, neurons contain uniquely high levels of non-CpG methylation, such that the total amounts of methylation in non-CpG contexts equals or surpasses the total amounts of methylation in CG contexts. Non-CpG methylation, unlike CpG methylation, cannot be maintained by DNMT1, and must be established by the de novo methyltransferase DNMT3A.One unique characteristic of non-CpG methylation compared to canonical CpG methylation is …
Understand And Predict Microbiome And Resistome Dynamics In Response To Perturbations Across Diverse Populations And Environments, Manish Boolchandani
Understand And Predict Microbiome And Resistome Dynamics In Response To Perturbations Across Diverse Populations And Environments, Manish Boolchandani
Arts & Sciences Electronic Theses and Dissertations
Complex microbial communities are at the interface of human, animal and environment interconnected ecosystem, where they can move within and between these entities. These microbial communities are mostly beneficial, maintaining the host health and homeostatic state. However, these communities can also serve as reservoirs of antibiotic resistance (AR) genes that may disseminate to pathogen bacteria, compromising the treatment options. Like other microbial communities, human gut microbiome is highly dynamic and can get acutely perturbed with the changes in the habitat, diet, lifestyle and disease. A perturbed gut community structure has profound impact on the host health and physiology. Use of …