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Articles 1 - 30 of 452

Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

Iron-Sulfur Cluster Biosynthesis In Methanogens, Cuiping Zhao Jun 2019

Iron-Sulfur Cluster Biosynthesis In Methanogens, Cuiping Zhao

LSU Doctoral Dissertations

Methanogens live in a syntrophic consortium with bacteria, taking advantage of the metabolic abilities of their syntrophic partners to overcome energetic barriers and break down compounds that they cannot digest by themselves. Interspecies electron transfer, which is a major type of microbial communication in syntrophic processes, improves methanogenesis and anaerobic oxidization of methane (AOM) processes involved in syntrophic consortia. These processes have a significant impact on the global carbon cycle. Most of the essential enzymes involved in methanogenesis are iron-sulfur proteins. Iron-sulfur clusters are one of the oldest and most versatile cofactors present in all domains of life. To date ...


A Chromosome Folding Intermediate At The Condensin-To-Cohesin Transition During Telophase, Kristin Abramo, Anne-Laure Valton, Sergey V. Venev, Hakan Ozadam, A. Nicole Fox, Job Dekker Jun 2019

A Chromosome Folding Intermediate At The Condensin-To-Cohesin Transition During Telophase, Kristin Abramo, Anne-Laure Valton, Sergey V. Venev, Hakan Ozadam, A. Nicole Fox, Job Dekker

University of Massachusetts Medical School Faculty Publications

Chromosome folding is extensively modulated as cells progress through the cell cycle. During mitosis, condensin complexes fold chromosomes in helically arranged nested loop arrays. In interphase, the cohesin complex generates loops that can be stalled at CTCF sites leading to positioned loops and topologically associating domains (TADs), while a separate process of compartmentalization drives the spatial segregation of active and inactive chromatin domains. We used synchronized cell cultures to determine how the mitotic chromosome conformation is transformed into the interphase state. Using Hi-C, chromatin binding assays, and immunofluorescence we show that by telophase condensin-mediated loops are lost and a transient ...


Structure-Based Design Of Hepatitis C Virus Vaccines That Elicit Neutralizing Antibody Responses To A Conserved Epitope, Brian G. Pierce, Elisabeth N. Boucher, Kurt H. Piepenbrink, Ejemel Monir, Chelsea A. Rapp, William D. Thomas Jr., Eric J. Sundberg, Zhiping Weng, Yan Wang Jun 2019

Structure-Based Design Of Hepatitis C Virus Vaccines That Elicit Neutralizing Antibody Responses To A Conserved Epitope, Brian G. Pierce, Elisabeth N. Boucher, Kurt H. Piepenbrink, Ejemel Monir, Chelsea A. Rapp, William D. Thomas Jr., Eric J. Sundberg, Zhiping Weng, Yan Wang

Kurt Piepenbrink

Despite recent advances in therapeutic options, hepatitis C virus (HCV) remains a severe global disease burden, and a vaccine can substantially reduce its incidence. Due to its extremely high sequence variability, HCV can readily escape the immune response; thus, an effective vaccine must target conserved, functionally important epitopes. Using the structure of a broadly neutralizing antibody in complex with a conserved linear epitope from the HCV E2 envelope glycoprotein (residues 412 to 423; epitope I), we performed structure-based design of immunogens to induce antibody responses to this epitope. This resulted in epitope-based immunogens based on a cyclic defensin protein, as ...


Crispr-Sonic: Targeted Somatic Oncogene Knock-In Enables Rapid In Vivo Cancer Modeling, Haiwei Mou, Deniz M. Ozata, Jordan L. Smith, Ankur Sheel, Suet-Yan Kwan, Soren Hough, Alper Kucukural, Zachary Kennedy, Yueying Cao, Wen Xue Apr 2019

Crispr-Sonic: Targeted Somatic Oncogene Knock-In Enables Rapid In Vivo Cancer Modeling, Haiwei Mou, Deniz M. Ozata, Jordan L. Smith, Ankur Sheel, Suet-Yan Kwan, Soren Hough, Alper Kucukural, Zachary Kennedy, Yueying Cao, Wen Xue

RNA Therapeutics Institute Publications

CRISPR/Cas9 has revolutionized cancer mouse models. Although loss-of-function genetics by CRISPR/Cas9 is well-established, generating gain-of-function alleles in somatic cancer models is still challenging because of the low efficiency of gene knock-in. Here we developed CRISPR-based Somatic Oncogene kNock-In for Cancer Modeling (CRISPR-SONIC), a method for rapid in vivo cancer modeling using homology-independent repair to integrate oncogenes at a targeted genomic locus. Using a dual guide RNA strategy, we integrated a plasmid donor in the 3'-UTR of mouse beta-actin, allowing co-expression of reporter genes or oncogenes from the beta-actin promoter. We showed that knock-in of oncogenic Ras and ...


Unified Methods For Feature Selection In Large-Scale Genomic Studies With Censored Survival Outcomes, Lauren Spirko-Burns, Karthik Devarajan Mar 2019

Unified Methods For Feature Selection In Large-Scale Genomic Studies With Censored Survival Outcomes, Lauren Spirko-Burns, Karthik Devarajan

COBRA Preprint Series

One of the major goals in large-scale genomic studies is to identify genes with a prognostic impact on time-to-event outcomes which provide insight into the disease's process. With rapid developments in high-throughput genomic technologies in the past two decades, the scientific community is able to monitor the expression levels of tens of thousands of genes and proteins resulting in enormous data sets where the number of genomic features is far greater than the number of subjects. Methods based on univariate Cox regression are often used to select genomic features related to survival outcome; however, the Cox model assumes proportional ...


Supervised Dimension Reduction For Large-Scale "Omics" Data With Censored Survival Outcomes Under Possible Non-Proportional Hazards, Lauren Spirko-Burns, Karthik Devarajan Mar 2019

Supervised Dimension Reduction For Large-Scale "Omics" Data With Censored Survival Outcomes Under Possible Non-Proportional Hazards, Lauren Spirko-Burns, Karthik Devarajan

COBRA Preprint Series

The past two decades have witnessed significant advances in high-throughput ``omics" technologies such as genomics, proteomics, metabolomics, transcriptomics and radiomics. These technologies have enabled simultaneous measurement of the expression levels of tens of thousands of features from individual patient samples and have generated enormous amounts of data that require analysis and interpretation. One specific area of interest has been in studying the relationship between these features and patient outcomes, such as overall and recurrence-free survival, with the goal of developing a predictive ``omics" profile. Large-scale studies often suffer from the presence of a large fraction of censored observations and potential ...


Data Analytics Pipeline For Rna Structure Analysis Via Shape, Quinn Nelson Mar 2019

Data Analytics Pipeline For Rna Structure Analysis Via Shape, Quinn Nelson

Student Research and Creative Activity Fair

Coxsackievirus B3 (CVB3) is a cardiovirulent enterovirus from the family Picornaviridae. The RNA genome houses an internal ribosome entry site (IRES) in the 5’ untranslated region (5’UTR) that enables cap-independent translation. Ample evidence suggests that the structure of the 5’UTR is a critical element for virulence. We probe RNA structure in solution using base-specific modifying agents such as dimethyl sulfate as well as backbone targeting agents such as N-methylisatoic anhydride used in Selective 2’-Hydroxyl Acylation Analyzed by Primer Extension (SHAPE). We have developed a pipeline that merges and evaluates base-specific and SHAPE data together with statistical analyses ...


Radiation Dose Estimation By Completely Automated Interpretation Of The Dicentric Chromosome Assay, Peter Rogan, Yanxin Li, Ben Shirley, Ruth Wilkins, Farrah Norton, Joan Knoll Jan 2019

Radiation Dose Estimation By Completely Automated Interpretation Of The Dicentric Chromosome Assay, Peter Rogan, Yanxin Li, Ben Shirley, Ruth Wilkins, Farrah Norton, Joan Knoll

Biochemistry Publications

Accuracy of the automated dicentric chromosome (DC) assay relies on metaphase image selection. This study validates a software framework to find the best image selection models that mitigate inter-sample variability. Evaluation methods to determine model quality include the Poisson goodness-of-fit of DC distributions for each sample, residuals after calibration curve fitting and leave-one-out dose estimation errors. The process iteratively searches a pool of selection model candidates by modifying statistical and filter cut-offs to rank the best candidates according to their respective evaluation scores. Evaluation scores minimize the sum of squared errors relative to the actual radiation dose of the calibration ...


Debrowser: Interactive Differential Expression Analysis And Visualization Tool For Count Data, Alper Kucukural, Onur Yukselen, Deniz M. Ozata, Melissa J. Moore, Manuel Garber Jan 2019

Debrowser: Interactive Differential Expression Analysis And Visualization Tool For Count Data, Alper Kucukural, Onur Yukselen, Deniz M. Ozata, Melissa J. Moore, Manuel Garber

Program in Bioinformatics and Integrative Biology Publications and Presentations

BACKGROUND: Sequencing data has become a standard measure of diverse cellular activities. For example, gene expression is accurately measured by RNA sequencing (RNA-Seq) libraries, protein-DNA interactions are captured by chromatin immunoprecipitation sequencing (ChIP-Seq), protein-RNA interactions by crosslinking immunoprecipitation sequencing (CLIP-Seq) or RNA immunoprecipitation (RIP-Seq) sequencing, DNA accessibility by assay for transposase-accessible chromatin (ATAC-Seq), DNase or MNase sequencing libraries. The processing of these sequencing techniques involves library-specific approaches. However, in all cases, once the sequencing libraries are processed, the result is a count table specifying the estimated number of reads originating from each genomic locus. Differential analysis to determine which loci ...


Automatic 13C Chemical Shift Reference Correction Of Protein Nmr Spectral Data Using Data Mining And Bayesian Statistical Modeling, Xi Chen Jan 2019

Automatic 13C Chemical Shift Reference Correction Of Protein Nmr Spectral Data Using Data Mining And Bayesian Statistical Modeling, Xi Chen

Theses and Dissertations--Molecular and Cellular Biochemistry

Nuclear magnetic resonance (NMR) is a highly versatile analytical technique for studying molecular configuration, conformation, and dynamics, especially of biomacromolecules such as proteins. However, due to the intrinsic properties of NMR experiments, results from the NMR instruments require a refencing step before the down-the-line analysis. Poor chemical shift referencing, especially for 13C in protein Nuclear Magnetic Resonance (NMR) experiments, fundamentally limits and even prevents effective study of biomacromolecules via NMR. There is no available method that can rereference carbon chemical shifts from protein NMR without secondary experimental information such as structure or resonance assignment.

To solve this problem, we ...


Transcription Factor Binding Site Clusters Identify Target Genes With Similar Tissue-Wide Expression And Buffer Against Mutations., Peter Rogan, Ruipeng Lu Jan 2019

Transcription Factor Binding Site Clusters Identify Target Genes With Similar Tissue-Wide Expression And Buffer Against Mutations., Peter Rogan, Ruipeng Lu

Biochemistry Publications

Background: The distribution and composition of cis-regulatory modules composed of transcription factor (TF) binding site (TFBS) clusters in promoters substantially determine gene expression patterns and TF targets. TF knockdown experiments have revealed that TF binding profiles and gene expression levels are correlated. We use TFBS features within accessible promoter intervals to predict genes with similar tissue-wide expression patterns and TF targets using Machine Learning (ML). Methods: Bray-Curtis Similarity was used to identify genes with correlated expression patterns across 53 tissues. TF targets from knockdown experiments were also analyzed by this approach to set up the ML framework. TFBSs were ...


The Impact Of Household Biocides And Antibiotics On Aquatic Microbial Community Composition, Abdulaziz Saud M Alrashdi Jan 2019

The Impact Of Household Biocides And Antibiotics On Aquatic Microbial Community Composition, Abdulaziz Saud M Alrashdi

Dissertations, Master's Theses and Master's Reports

Triclosan (TCS) is antimicrobial agent that is used in a lot of consumer products, including toothpaste, liquid and bar soap, and cosmetics. TCS has been found in many lakes and rivers in the United States. However, The Food and Drug Administration (FDA) banned TCS recently and it will no longer be used in household products. Despite the recent ban, TCS is known to persist in the environment and may have long-term impacts. We conducted an experiment on using fresh water from three locations Houghton, Green Bay and the Huron Mountains. Our goals in the study is to assess the impact ...


Comparative Analysis Of Dna Isolation Methods For The Human Microbiome, Hannah Chatwin Jan 2019

Comparative Analysis Of Dna Isolation Methods For The Human Microbiome, Hannah Chatwin

Undergraduate Honors Theses

The human microbiome is made up of millions of microbes coexisting in and on us with involvement in health and disease. The exact mechanisms by which this occurs have yet to be fully elucidated. Due to high variability in the composition of each person’s microbiome, it requires large numbers of people to begin to identify some of these processes. A major road block to generating large data sets for analysis is the high cost of DNA isolation from large collections of phenotypically well-characterized human subjects. This study explores the possible application of an inexpensive alternative DNA isolation method utilizing ...


The Trim-Nhl Protein Nhl-2 Is A Co-Factor In The Nuclear And Somatic Rnai Pathways In C. Elegans, Gregory M. Davis, Shikui Tu, Jacqueline A. Wilce, Julie M. Claycomb, Zhiping Weng, Peter R. Boag Dec 2018

The Trim-Nhl Protein Nhl-2 Is A Co-Factor In The Nuclear And Somatic Rnai Pathways In C. Elegans, Gregory M. Davis, Shikui Tu, Jacqueline A. Wilce, Julie M. Claycomb, Zhiping Weng, Peter R. Boag

Program in Bioinformatics and Integrative Biology Publications and Presentations

Proper regulation of germline gene expression is essential for fertility and maintaining species integrity. In the C. elegans germline, a diverse repertoire of regulatory pathways promote the expression of endogenous germline genes and limit the expression of deleterious transcripts to maintain genome homeostasis. Here we show that the conserved TRIM-NHL protein, NHL-2, plays an essential role in the C. elegans germline, modulating germline chromatin and meiotic chromosome organization. We uncover a role for NHL-2 as a co-factor in both positively (CSR-1) and negatively (HRDE-1) acting germline 22G-small RNA pathways and the somatic nuclear RNAi pathway. Furthermore, we demonstrate that NHL-2 ...


Potent Cas9 Inhibition In Bacterial And Human Cells By Acriic4 And Acriic5 Anti-Crispr Proteins, Jooyoung Lee, Aamir Mir, Alireza Edraki, Bianca Garcia, Nadia Amrani, Hannah E. Lou, Ildar Gainetdinov, April Pawluk, Raed Ibraheim, Xin D. Gao, Pengpeng Liu, Alan R. Davidson, Karen L. Maxwell, Erik J. Sontheimer Dec 2018

Potent Cas9 Inhibition In Bacterial And Human Cells By Acriic4 And Acriic5 Anti-Crispr Proteins, Jooyoung Lee, Aamir Mir, Alireza Edraki, Bianca Garcia, Nadia Amrani, Hannah E. Lou, Ildar Gainetdinov, April Pawluk, Raed Ibraheim, Xin D. Gao, Pengpeng Liu, Alan R. Davidson, Karen L. Maxwell, Erik J. Sontheimer

Open Access Articles

In their natural settings, CRISPR-Cas systems play crucial roles in bacterial and archaeal adaptive immunity to protect against phages and other mobile genetic elements, and they are also widely used as genome engineering technologies. Previously we discovered bacteriophage-encoded Cas9-specific anti-CRISPR (Acr) proteins that serve as countermeasures against host bacterial immunity by inactivating their CRISPR-Cas systems (A. Pawluk, N. Amrani, Y. Zhang, B. Garcia, et al., Cell 167:1829-1838.e9, 2016, https://doi.org/10.1016/j.cell.2016.11.017). We hypothesized that the evolutionary advantages conferred by anti-CRISPRs would drive the widespread occurrence of these proteins in nature (K ...


Two Contrasting Classes Of Nucleolus-Associated Domains In Mouse Fibroblast Heterochromatin, Anastassiia Vertii, Jianhong Ou, Jun Yu, Aimin Yan, Hervé Pagès, Haibo Liu, Lihua Julie Zhu, Paul D. Kaufman Dec 2018

Two Contrasting Classes Of Nucleolus-Associated Domains In Mouse Fibroblast Heterochromatin, Anastassiia Vertii, Jianhong Ou, Jun Yu, Aimin Yan, Hervé Pagès, Haibo Liu, Lihua Julie Zhu, Paul D. Kaufman

University of Massachusetts Medical School Faculty Publications

In interphase eukaryotic cells, almost all heterochromatin is located adjacent to the nucleolus or to the nuclear lamina, thus defining Nucleolus Associated Domains (NADs) and Lamina Associated Domains (LADs), respectively. Here, we determined the first genome-scale map of murine NADs in mouse embryonic fibroblasts (MEFs) via deep sequencing of chromatin associated with purified nucleoli. We developed a Bioconductor package called NADfinder and demonstrated that it identifies NADs more accurately than other peak-calling tools, due to its critical feature of chromosome-level local baseline correction. We detected two distinct classes of NADs. Type I NADs associate frequently with both the nucleolar periphery ...


Genetic And Epigenetic Investigations On Pulmonary Hypertension Syndrome In Meat Type- Chickens, Khaloud Alzahrani Dec 2018

Genetic And Epigenetic Investigations On Pulmonary Hypertension Syndrome In Meat Type- Chickens, Khaloud Alzahrani

Theses and Dissertations

This dissertation presents a collection of studies that investigate the genetic and epigenetic associations to ascites phenotype in broiler chickens. Ascites is a significant metabolic disease associated with fast-growing meat-type chickens (broilers) and is a terminal result of pulmonary hypertension syndrome PHS. It is a multi-factorial syndrome caused by interactions between genetic, physiological, environmental, and managemental factors. It was estimated that ascites accounts for losses of about US$1 billion annually worldwide and for over 25% of broilers mortality. Although traditional and molecular genetic methods in the selection and in performance improvements, has greatly reduced ascites frequency, yet it has ...


Functional Consequence Of Psat1 Association On Pkm2'S Inherent Enzymatic Activity., Alexis Avidan Vega Dec 2018

Functional Consequence Of Psat1 Association On Pkm2'S Inherent Enzymatic Activity., Alexis Avidan Vega

Electronic Theses and Dissertations

Pyruvate kinase M2 (PKM2) is predominantly found in tumors, where it allows the cancer cell to adapt to metabolic conditions through allosteric regulation of its activity. We recently discovered that phosphoserine aminotransferase 1 (PSAT1) associates with and activates PKM2. Here, I sought to affirm PSAT1's ability to increase PKM2 activity through kinetic and association studies of wild-type or mutant PKM2 enzymes. I demonstrate that His-tagged WT and mutant PKM2 enzymes are active, exhibit different kinetics, yet cannot be activated by PSAT1. Comparison studies using untagged WT PKM2 suggest that inclusion of the His-tag disrupts PSAT1 association. In support, pull-down ...


Multi-Resolution Analysis Of Large Molecular Structures And Interactions, Kasra Manavi Nov 2018

Multi-Resolution Analysis Of Large Molecular Structures And Interactions, Kasra Manavi

Computer Science ETDs

Simulation of large molecular structures and their interactions has become a major component of modern biomolecular research. Methods to simulate these type of molecules span a wide array of resolutions, from all atom molecular dynamics to model interaction energetics to systems of linear equations to evaluate population kinetics. In recent years, there has been an acceleration of molecular structural information production, primarily from x-ray crystallography and electron microscopy. This data has provided modelers the ability to produce better representations of these molecular structures. The purpose of this research is to take advantage of this information to develop multi-resolution models for ...


Mutations In Influenza A Virus Neuraminidase And Hemagglutinin Confer Resistance Against A Broadly Neutralizing Hemagglutinin Stem Antibody, Kristina L. Prachanronarong, Aneth S. Canale, Ping Liu, Mohan Somasundaran, Shurong Hou, Yu-Ping Poh, Thomas Han, Quan Zhu, Nicholas Renzette, Konstantin B. Zeldovich, Timothy F. Kowalik, Nese Kurt Yilmaz, Jeffrey D. Jensen, Daniel N. Bolon, Wayne A. Marasco, Robert W. Finberg, Celia A. Schiffer, Jennifer P. Wang Oct 2018

Mutations In Influenza A Virus Neuraminidase And Hemagglutinin Confer Resistance Against A Broadly Neutralizing Hemagglutinin Stem Antibody, Kristina L. Prachanronarong, Aneth S. Canale, Ping Liu, Mohan Somasundaran, Shurong Hou, Yu-Ping Poh, Thomas Han, Quan Zhu, Nicholas Renzette, Konstantin B. Zeldovich, Timothy F. Kowalik, Nese Kurt Yilmaz, Jeffrey D. Jensen, Daniel N. Bolon, Wayne A. Marasco, Robert W. Finberg, Celia A. Schiffer, Jennifer P. Wang

Schiffer Lab Publications

Influenza A virus (IAV), a major cause of human morbidity and mortality, continuously evolves in response to selective pressures. Stem-directed, broadly neutralizing antibodies (sBnAbs) targeting influenza hemagglutinin (HA) are a promising therapeutic strategy, but neutralization escape mutants can develop. We used an integrated approach combining viral passaging, deep sequencing, and protein structural analyses to define escape mutations and mechanisms of neutralization escape in vitro for the F10 sBnAb. IAV was propagated with escalating concentrations of F10 over serial passages in cultured cells to select for escape mutations. Viral sequence analysis revealed three mutations in HA and one in neuraminidase (NA ...


The Goldilocks Approach: A Review Of Employing Design Of Experiments In Prokaryotic Recombinant Protein Production, Albert Uhoraningoga, Gemma K. Kinsella, Gary T. Henehan, Barry Ryan Oct 2018

The Goldilocks Approach: A Review Of Employing Design Of Experiments In Prokaryotic Recombinant Protein Production, Albert Uhoraningoga, Gemma K. Kinsella, Gary T. Henehan, Barry Ryan

Articles

The production of high yields of soluble recombinant protein is one of the main objectives of protein biotechnology. Several factors, such as expression system, vector, host, media composition and induction conditions can influence recombinant protein yield. Identifying the most important factors for optimum protein expression may involve significant investment of time and considerable cost. To address this problem, statistical models such as Design of Experiments (DoE) have been used to optimise recombinant protein production. This review examines the application of DoE in the production of recombinant proteins in prokaryotic expression systems with specific emphasis on media composition and culture conditions ...


The Temporal Landscape Of Recursive Splicing During Pol Ii Transcription Elongation In Human Cells, Xiao-Ou Zhang, Yu Fu, Haiwei Mou, Wen Xue, Zhiping Weng Aug 2018

The Temporal Landscape Of Recursive Splicing During Pol Ii Transcription Elongation In Human Cells, Xiao-Ou Zhang, Yu Fu, Haiwei Mou, Wen Xue, Zhiping Weng

Program in Bioinformatics and Integrative Biology Publications and Presentations

Recursive splicing (RS) is an evolutionarily conserved process of removing long introns via multiple steps of splicing. It was first discovered in Drosophila and recently proven to occur also in humans. The detailed mechanism of recursive splicing is not well understood, in particular, whether it is kinetically coupled with transcription. To investigate the dynamic process that underlies recursive splicing, we systematically characterized 342 RS sites in three human cell types using published time-series data that monitored synchronized Pol II elongation and nascent RNA production with 4-thiouridine labeling. We found that half of the RS events occurred post-transcriptionally with long delays ...


Differential Analysis Of Chromatin Accessibility And Histone Modifications For Predicting Mouse Developmental Enhancers, Shaliu Fu, Qin Wang, Jill E. Moore, Michael J. Purcaro, Henry E. Pratt, Kaili Fan, Cuihua Gu, Cizhong Jiang, Ruixin Zhu, Anshul Kundaje, Aiping Lu, Zhiping Weng Aug 2018

Differential Analysis Of Chromatin Accessibility And Histone Modifications For Predicting Mouse Developmental Enhancers, Shaliu Fu, Qin Wang, Jill E. Moore, Michael J. Purcaro, Henry E. Pratt, Kaili Fan, Cuihua Gu, Cizhong Jiang, Ruixin Zhu, Anshul Kundaje, Aiping Lu, Zhiping Weng

Program in Bioinformatics and Integrative Biology Publications and Presentations

Enhancers are distal cis-regulatory elements that modulate gene expression. They are depleted of nucleosomes and enriched in specific histone modifications; thus, calling DNase-seq and histone mark ChIP-seq peaks can predict enhancers. We evaluated nine peak-calling algorithms for predicting enhancers validated by transgenic mouse assays. DNase and H3K27ac peaks were consistently more predictive than H3K4me1/2/3 and H3K9ac peaks. DFilter and Hotspot2 were the best DNase peak callers, while HOMER, MUSIC, MACS2, DFilter and F-seq were the best H3K27ac peak callers. We observed that the differential DNase or H3K27ac signals between two distant tissues increased the area under the precision-recall ...


Microbial Ecology Of South Florida Surface Waters: Examining The Potential For Anthropogenic Influences, Chase P. Donnelly Aug 2018

Microbial Ecology Of South Florida Surface Waters: Examining The Potential For Anthropogenic Influences, Chase P. Donnelly

HCNSO Student Theses and Dissertations

South Florida contains one of the largest subtropical wetlands in the world, and yet not much is known about the microbes that live in these surface waters. These microbes play an important role in chemical cycling and maintaining good water quality for both human and ecosystem health. The hydrology of Florida’s surface waters is tightly regulated with the use of canal and levee systems run by the US Army Corps of Engineers and The South Florida Water Management District. These canals run through the Everglades, agriculture, and urban environments to control water levels in Lake Okeechobee, the Water Conservation ...


Deciphering The Role Of Human Arylamine N-Acetyltransferase 1 (Nat1) In Breast Cancer Cell Metabolism Using A Systems Biology Approach., Samantha Marie Carlisle Aug 2018

Deciphering The Role Of Human Arylamine N-Acetyltransferase 1 (Nat1) In Breast Cancer Cell Metabolism Using A Systems Biology Approach., Samantha Marie Carlisle

Electronic Theses and Dissertations

Background: Human arylamine N-acetyltransferase 1 (NAT1) is a phase II xenobiotic metabolizing enzyme found in almost all tissues. NAT1 can additionally hydrolyze acetyl-coenzyme A (acetyl-CoA) in the absence of an arylamine substrate. NAT1 expression varies inter-individually and is elevated in several cancers including estrogen receptor positive (ER+) breast cancers. Additionally, multiple studies have shown the knockdown of NAT1, by both small molecule inhibition and siRNA methods, in breast cancer cells leads to decreased invasive ability and proliferation and decreased anchorage-independent colony formation. However, the exact mechanism by which NAT1 expression affects cancer risk and progression remains unclear. Additionally, consequences ...


Bayesian Analytical Approaches For Metabolomics : A Novel Method For Molecular Structure-Informed Metabolite Interaction Modeling, A Novel Diagnostic Model For Differentiating Myocardial Infarction Type, And Approaches For Compound Identification Given Mass Spectrometry Data., Patrick J. Trainor Aug 2018

Bayesian Analytical Approaches For Metabolomics : A Novel Method For Molecular Structure-Informed Metabolite Interaction Modeling, A Novel Diagnostic Model For Differentiating Myocardial Infarction Type, And Approaches For Compound Identification Given Mass Spectrometry Data., Patrick J. Trainor

Electronic Theses and Dissertations

Metabolomics, the study of small molecules in biological systems, has enjoyed great success in enabling researchers to examine disease-associated metabolic dysregulation and has been utilized for the discovery biomarkers of disease and phenotypic states. In spite of recent technological advances in the analytical platforms utilized in metabolomics and the proliferation of tools for the analysis of metabolomics data, significant challenges in metabolomics data analyses remain. In this dissertation, we present three of these challenges and Bayesian methodological solutions for each. In the first part we develop a new methodology to serve a basis for making higher order inferences in metabolomics ...


Computational Analysis Of Genomic Variants Affecting Predicted Microrna:Target Interactions In Prostate Cancer., Angélica Paola Hernández Pérez Jul 2018

Computational Analysis Of Genomic Variants Affecting Predicted Microrna:Target Interactions In Prostate Cancer., Angélica Paola Hernández Pérez

KGI Theses and Dissertations

Prostate cancer (PCa) is the most common cancer of men in the United States and is third only to lung and colon as a cause of cancer death. Clinical behavior of the disease is variable and the combination of prostate-specific antigen (PSA) screening and Gleason score staging are currently the best available molecular and pathology tools to predict outcomes. Cancer biology research establishes microRNAs (miRNAs) as key molecular components in both normal and pathological states. Thus, elucidating miRNAs perturbed by genomic alterations will expand our understanding of the molecular taxonomy of PCa with the aim to complement current practices in ...


Extending Chemical Perturbations Of The Ubiquitin Fitness Landscape In A Classroom Setting Reveals New Constraints On Sequence Tolerance, David Mavor, Daniel N. Bolon, Martin Kampmann, James S. Fraser Jul 2018

Extending Chemical Perturbations Of The Ubiquitin Fitness Landscape In A Classroom Setting Reveals New Constraints On Sequence Tolerance, David Mavor, Daniel N. Bolon, Martin Kampmann, James S. Fraser

Open Access Articles

Although the primary protein sequence of ubiquitin (Ub) is extremely stable over evolutionary time, it is highly tolerant to mutation during selection experiments performed in the laboratory. We have proposed that this discrepancy results from the difference between fitness under laboratory culture conditions and the selective pressures in changing environments over evolutionary timescales. Building on our previous work (Mavor et al., 2016), we used deep mutational scanning to determine how twelve new chemicals (3-Amino-1,2,4-triazole, 5-fluorocytosine, Amphotericin B, CaCl2, Cerulenin, Cobalt Acetate, Menadione, Nickel Chloride, p-Fluorophenylalanine, Rapamycin, Tamoxifen, and Tunicamycin) reveal novel mutational sensitivities of ubiquitin residues. Collectively, our ...


Elimination Of Pcr Duplicates In Rna-Seq And Small Rna-Seq Using Unique Molecular Identifiers, Yu Fu, Pei-Hsuan Wu, Timothy J. Beane, Phillip D. Zamore, Zhiping Weng Jul 2018

Elimination Of Pcr Duplicates In Rna-Seq And Small Rna-Seq Using Unique Molecular Identifiers, Yu Fu, Pei-Hsuan Wu, Timothy J. Beane, Phillip D. Zamore, Zhiping Weng

Open Access Articles

BACKGROUND: RNA-seq and small RNA-seq are powerful, quantitative tools to study gene regulation and function. Common high-throughput sequencing methods rely on polymerase chain reaction (PCR) to expand the starting material, but not every molecule amplifies equally, causing some to be overrepresented. Unique molecular identifiers (UMIs) can be used to distinguish undesirable PCR duplicates derived from a single molecule and identical but biologically meaningful reads from different molecules.

RESULTS: We have incorporated UMIs into RNA-seq and small RNA-seq protocols and developed tools to analyze the resulting data. Our UMIs contain stretches of random nucleotides whose lengths sufficiently capture diverse molecule species ...


Dynamic Placement Of The Linker Histone H1 Associated With Nucleosome Arrangement And Gene Transcription In Early Drosophila Embryonic Development, Jian Hu, Liang Gu, Youqiong Ye, Meizhu Zheng, Zhu Xu, Jing Lin, Yanhua Du, Mengxue Tian, Lifang Luo, Beibei Wang, Xiaobai Zhang, Zhiping Weng, Cizhong Jiang Jul 2018

Dynamic Placement Of The Linker Histone H1 Associated With Nucleosome Arrangement And Gene Transcription In Early Drosophila Embryonic Development, Jian Hu, Liang Gu, Youqiong Ye, Meizhu Zheng, Zhu Xu, Jing Lin, Yanhua Du, Mengxue Tian, Lifang Luo, Beibei Wang, Xiaobai Zhang, Zhiping Weng, Cizhong Jiang

Open Access Articles

The linker histone H1 is critical to maintenance of higher-order chromatin structures and to gene expression regulation. However, H1 dynamics and its functions in embryonic development remain unresolved. Here, we profiled gene expression, nucleosome positions, and H1 locations in early Drosophila embryos. The results show that H1 binding is positively correlated with the stability of beads-on-a-string nucleosome organization likely through stabilizing nucleosome positioning and maintaining nucleosome spacing. Strikingly, nucleosomes with H1 placement deviating to the left or the right relative to the dyad shift to the left or the right, respectively, during early Drosophila embryonic development. H1 occupancy on genic ...