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Optimized Rna-Targeting Crispr/Cas13d Technology Outperforms Shrna In Identifying Functional Circrnas, Yang Zhang, Tuan M. Nguyen, Xiao-Ou Zhang, Limei Wang, Tin Phan, John G. Clohessy, Pier Paolo Pandolfi 2021 Harvard Medical School

Optimized Rna-Targeting Crispr/Cas13d Technology Outperforms Shrna In Identifying Functional Circrnas, Yang Zhang, Tuan M. Nguyen, Xiao-Ou Zhang, Limei Wang, Tin Phan, John G. Clohessy, Pier Paolo Pandolfi

Open Access Publications by UMMS Authors

Short hairpin RNAs (shRNAs) are used to deplete circRNAs by targeting back-splicing junction (BSJ) sites. However, frequent discrepancies exist between shRNA-mediated circRNA knockdown and the corresponding biological effect, querying their robustness. By leveraging CRISPR/Cas13d tool and optimizing the strategy for designing single-guide RNAs against circRNA BSJ sites, we markedly enhance specificity of circRNA silencing. This specificity is validated in parallel screenings by shRNA and CRISPR/Cas13d libraries. Using a CRISPR/Cas13d screening library targeting > 2500 human hepatocellular carcinoma-related circRNAs, we subsequently identify a subset of sorafenib-resistant circRNAs. Thus, CRISPR/Cas13d represents an effective approach for high-throughput study of functional ...


Differential Gene Expression Analysis Of Rodents Exposed To Long-Term Space Flight And Insights Into Physiological Effects, Jonathan Oribello 2021 San Jose State University

Differential Gene Expression Analysis Of Rodents Exposed To Long-Term Space Flight And Insights Into Physiological Effects, Jonathan Oribello

Master's Projects

Space travel presents inherent risks to human health and a better understanding of space biology is required to mitigate harm in an oncoming age of increased space travel. Omics analysis will play a central role in better understanding human health in space. In this project, differential gene expression analysis was performed on GLDS-104, an open science dataset provided by NASA’s GeneLab. GeneLab’s RNA-Seq Consensus Pipeline was implemented using Nextflow, performed on San Jose State University’s College of Science High Performance Computing Cluster, and optimized for computational resource efficiency. Comparison of the Nextflow implemention developed in this project ...


Meta-Analysis Of Natural Vs Pharmaceutical Interventions For Alzheimer's Disease, Tamara Vrublevskaya 2021 San Jose State University

Meta-Analysis Of Natural Vs Pharmaceutical Interventions For Alzheimer's Disease, Tamara Vrublevskaya

Master's Projects

The purpose of this research is to present a way to compare interventions by collecting all available drug clinical trials for a disease of interest. The assessment is done using Meta-Analysis, a method for evaluating data from several studies to arrive at a combined estimate of treatment effect. The evaluation is done in R on a given set of studies to answer the question – which Alzheimer's Disease intervention (pharmaceutical vs. natural) show better outcomes and fewer adverse effects. The research covers many types of interventions across diverse patient populations. On a small subset of papers, natural treatments showed better ...


Polya: A Tool For Adjudicating Competing Annotations Of Biological Sequences, Kaitlin Carey 2021 University of Montana

Polya: A Tool For Adjudicating Competing Annotations Of Biological Sequences, Kaitlin Carey

Graduate Student Theses, Dissertations, & Professional Papers

Annotation of a biological sequence is usually performed by aligning that sequence to a database of known sequence elements. When that database contains elements that are highly similar to each other, the proper annotation may be ambiguous, because several entries in the database produce high-scoring alignments. Typical annotation methods work by assigning a label based on the candidate annotation with the highest alignment score; this can overstate annotation certainty, mislabel boundaries, and fails to identify large scale rearrangements or insertions within the annotated sequence. Here, I present a new software tool, PolyA, that adjudicates between competing alignment-based annotations by computing ...


Characterizing Patterns Of Genomic Variation In The Threatened Utah Prairie Dog: Implications For Conservation And Management, Rachael M. Giglio, Tonie E. Rocke, Jorge E. Osorio, Emily Latch 2021 University of Wisconsin - Milwaukee

Characterizing Patterns Of Genomic Variation In The Threatened Utah Prairie Dog: Implications For Conservation And Management, Rachael M. Giglio, Tonie E. Rocke, Jorge E. Osorio, Emily Latch

Biological Sciences Faculty Articles

Utah prairie dogs (Cynomys parvidens) are federally threatened due to eradication campaigns, habitat destruction, and outbreaks of plague. Today, Utah prairie dogs exist in small, isolated populations, making them less demographically stable and more susceptible to erosion of genetic variation by genetic drift. We characterized patterns of genetic structure at neutral and putatively adaptive loci in order to evaluate the relative effects of genetic drift and local adaptation on population divergence. We sampled individuals across the Utah prairie dog species range and generated 2,955 single nucleotide polymorphisms (SNPs) using double digest restriction site associated DNA sequencing (ddRAD). Genetic diversity ...


Soda: An Open-Source Library For Visualizing Biological Sequence Annotation, Jack W. Roddy, Travis J. Wheeler 2021 The University Of Montana

Soda: An Open-Source Library For Visualizing Biological Sequence Annotation, Jack W. Roddy, Travis J. Wheeler

Graduate Student Theses, Dissertations, & Professional Papers

Genome annotation is the process of identifying and labeling known genetic sequences or features within a genome. Across the various subfields within modern molecular biology, there is a common need for the visualization of such annotations. Genomic data is often visualized on web browser platforms, providing users with easy access to visualization tools without the need for installing any software or, in many cases, underlying datasets. While there exists a broad range of web-based visualization tools, there is, to my knowledge, no lightweight, modern library tailored towards the visualization of genomic data. Instead, developers charged with the task of producing ...


Biological Control And Microbial Ecology Draft Genome Sequence Data Of Glutamicibacter Sp. Fbe-19, A Bacterium Antagonistic To The Plant Pathogen Erwinia Tracheiphila, Benzhong Fu, Olakunle Olawole, Gwyn A. Beattie 2021 Iowa State University

Biological Control And Microbial Ecology Draft Genome Sequence Data Of Glutamicibacter Sp. Fbe-19, A Bacterium Antagonistic To The Plant Pathogen Erwinia Tracheiphila, Benzhong Fu, Olakunle Olawole, Gwyn A. Beattie

Plant Pathology and Microbiology Publications

Glutamicibacter sp.FBE-19 was isolated based on its strong antagonism to the cucurbit bacterial blight pathogen Erwinia tracheiphila on plates. Members of the Glutamicibacter genus can promote plant growth under saline conditions and antagonize fungi on plates via chitinolytic activity; however, their production of antibacterial compounds has not been examined. Here, we report the genome sequence of strain FBE-19. The genome is 3.85 Mbp with a G+C content of 60.1% and comprises 3,791 genes. Genes that may contribute to its antagonistic activity include genes for the secondary metabolites stenothricin, salinosporamide A, a second β-lactone compound, and ...


The Causes And Control Measures Of Extended Spectrum Beta-Lactamase Producing Enterobacteriaceae In Long-Term Care Facilities, Ismaila Olatunji Sule 2021 Walden University

The Causes And Control Measures Of Extended Spectrum Beta-Lactamase Producing Enterobacteriaceae In Long-Term Care Facilities, Ismaila Olatunji Sule

Walden Dissertations and Doctoral Studies

Due to extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE), infections among residents are increasing in long-term care facilities (LTCFs), resulting in high rate of morbidity and healthcare costs. ESBL-PE resists empirical antibiotics and reduces treatment options, and a designated infection control team is unavailable to prevent the prevalence of the disease. Ecological theory guided this study. A systematic review and meta-analysis were conducted to characterize the causes of ESBL-PE and evaluate the infection control strategies within LTCFs. Multiple regression analysis (MRA) was included as supplementary statistical analysis to identify relationships between LTCFs, geographical locations, infection control measures (ICMs), and ESBL-PE. A systematic search ...


Population Genetics Of A Reintroduced Fisher (Pekania Pennanti) Population In West Virginia, Caroline E. Harms 2021 West Virginia University

Population Genetics Of A Reintroduced Fisher (Pekania Pennanti) Population In West Virginia, Caroline E. Harms

Graduate Theses, Dissertations, and Problem Reports

Fishers (Pekania pennanti) were reintroduced in West Virginia in 1969 with no population wide genetic analysis ever having been conducted. Genetic analysis of reintroduced populations is vital to assess genetic diversity as an indicative of population viability. My objective was to collect fisher samples throughout West Virginia, nearby states where fisher may be migrating (PA and NY), and the New Hampshire source population to provide a full genetic interpretation of the reintroduced West Virginia population. Genetic analysis was used to measure genetic diversity, admixture or delineation of subpopulations, and effective population size. Sample location and genetic data were combined to ...


Loss-Of-Function Genomic Variants Highlight Potential Therapeutic Targets For Cardiovascular Disease, Jonas B. Nielsen, Oren Rom, Ida Surakka, Sarah E. Graham, Wei Zhou, Tanmoy Roychowdhury, Lars G. Fritsche, Sarah A. Gagliano Taliun, Carlo Sidore, Yuhao Liu, Maiken E. Gabrielsen, Anne Heidi Skogholt, Brooke Wolford, William Overton, Ying Zhao, Jin Chen, He Zhang, Whitney E. Hornsby, Akua Acheampong, Austen Grooms, Amanda Schaefer, Gregory J. M. Zajac, Luis Villacorta, Jifeng Zhang, Ben Brumpton, Mari Løset, Vivek Rai, Pia R. Lundegaard, Morten S. Olesen, Kent D. Taylor, Donna K. Arnett 2020 University of Michigan

Loss-Of-Function Genomic Variants Highlight Potential Therapeutic Targets For Cardiovascular Disease, Jonas B. Nielsen, Oren Rom, Ida Surakka, Sarah E. Graham, Wei Zhou, Tanmoy Roychowdhury, Lars G. Fritsche, Sarah A. Gagliano Taliun, Carlo Sidore, Yuhao Liu, Maiken E. Gabrielsen, Anne Heidi Skogholt, Brooke Wolford, William Overton, Ying Zhao, Jin Chen, He Zhang, Whitney E. Hornsby, Akua Acheampong, Austen Grooms, Amanda Schaefer, Gregory J. M. Zajac, Luis Villacorta, Jifeng Zhang, Ben Brumpton, Mari Løset, Vivek Rai, Pia R. Lundegaard, Morten S. Olesen, Kent D. Taylor, Donna K. Arnett

Epidemiology Faculty Publications

Pharmaceutical drugs targeting dyslipidemia and cardiovascular disease (CVD) may increase the risk of fatty liver disease and other metabolic disorders. To identify potential novel CVD drug targets without these adverse effects, we perform genome-wide analyses of participants in the HUNT Study in Norway (n = 69,479) to search for protein-altering variants with beneficial impact on quantitative blood traits related to cardiovascular disease, but without detrimental impact on liver function. We identify 76 (11 previously unreported) presumed causal protein-altering variants associated with one or more CVD- or liver-related blood traits. Nine of the variants are predicted to result in loss-of-function of ...


Bioinformatics Metadata Extraction For Machine Learning Analysis, Zachary Tom 2020 San Jose State University

Bioinformatics Metadata Extraction For Machine Learning Analysis, Zachary Tom

Master's Projects

Next generation sequencing (NGS) has revolutionized the biological sciences. Today, entire genomes can be rapidly sequenced, enabling advancements in personalized medicine, genetic diseases, and more. The National Center for Biotechnology Information (NCBI) hosts the Sequence Read Archive (SRA) containing vast amounts of valuable NGS data. Recently, research has shown that sequencing errors in conventional NGS workflows are key confounding factors for detecting mutations. Various steps such as sample handling and library preparation can introduce artifacts that affect the accuracy of calling rare mutations. Thus, there is a need for more insight into the exact relationship between various steps of the ...


The Deleterious F109s Mutation Disrupts Binding Of Sex-Determining Region Y With Dna, Mohammed Baqur S. Al-Shuhaib MBSA 2020 Al-Qasim Green University

The Deleterious F109s Mutation Disrupts Binding Of Sex-Determining Region Y With Dna, Mohammed Baqur S. Al-Shuhaib Mbsa

Karbala International Journal of Modern Science

Sex-determining region Y (SRY) protein is the master switch in the initiation of male sex differentiation. Mutation in SRY gene results in ambiguous genitalia and abnormalities in reproductive organs. Its function is mainly controlled by its high mobility group (HMG) box. Damage to the HMG box may cause dysfunction of the SRY protein, which may, in turn, lead to sex reversal. This study was conducted to prioritize the deleterious effects of the non-synonymous single nucleotide polymorphisms (nsSNPs) on SRY protein. A series of computational tools were applied to predict nsSNPs with the most harmful effects on protein structure, function, and ...


Molecular Identification, Antioxidant Efficacy Of Phenolic Compounds, And Antimicrobial Activity Of Beta-Carotene Isolated From Fruiting Bodies Of Suillus Sp, Shimal Yonuis Abdulhadi, Raghad Nawaf Gergees, Ghazwan Qasim Hasan 2020 University of Mosul

Molecular Identification, Antioxidant Efficacy Of Phenolic Compounds, And Antimicrobial Activity Of Beta-Carotene Isolated From Fruiting Bodies Of Suillus Sp, Shimal Yonuis Abdulhadi, Raghad Nawaf Gergees, Ghazwan Qasim Hasan

Karbala International Journal of Modern Science

Suillus species, in general, are edible mushrooms, and environmentally important that are associated mostly with pine trees in the tropics regions. These fungi considered a remarkable source of phenolic compounds that play a crucial role as antioxidants which may reduce the risk of most human chronic diseases such as cancer, diabetes, asthma, atherosclerosis, Alzheimer, and others. On the other hand, carotenoids (β carotene) are the most popular natural pigments which play an important role to protect the plants from photo-oxidative reactions. In human, these compounds prevent oxidative stress and expects to have antimicrobial activity. Here, the phenolic compounds were extracted ...


Pathway‐Extended Gene Expression Signatures Integrate Novel Biomarkers That Improve Predictions Of Patient Responses To Kinase Inhibitors, Ashis Bagchee‐Clark, Eliseos J. Mucaki, Tyson Whitehead, Peter Rogan 2020 Western University

Pathway‐Extended Gene Expression Signatures Integrate Novel Biomarkers That Improve Predictions Of Patient Responses To Kinase Inhibitors, Ashis Bagchee‐Clark, Eliseos J. Mucaki, Tyson Whitehead, Peter Rogan

Biochemistry Publications

Cancer chemotherapy responses have been related to multiple pharmacogenetic biomarkers, often for the same drug. This study utilizes machine learning to derive multi‐gene expression signatures that predict individual patient responses to specific tyrosine kinase inhibitors, including erlotinib, gefitinib, sorafenib, sunitinib, lapatinib and imatinib. Support vector machine (SVM) learning was used to train mathematical models that distinguished sensitivity from resistance to these drugs using a novel systems biology‐based approach. This began with expression of genes previously implicated in specific drug responses, then expanded to evaluate genes whose products were related through biochemical pathways and interactions. Optimal pathway‐extended SVMs ...


Observed Defects Of Swiss Cheese Based On The Microbiome Contribution To The Production Of Organic Acids, Vannessa D. Campfield 2020 Boise State University

Observed Defects Of Swiss Cheese Based On The Microbiome Contribution To The Production Of Organic Acids, Vannessa D. Campfield

Boise State University Theses and Dissertations

The United States Department of Agriculture downgrades on the order of 17% of all Swiss cheese produced in the United States due to defects. Many of these defects are related to improper eye formation, number, distribution, or size; leading to an industry loss of over $69 million per annum. The microbiome in Swiss-type cheeses plays a significant role in eye development due to production of organic acids and gaseous emissions contingent on bacterial abundance and phenotype. The relationship between bacteria and the organic acids they produce leading to Swiss cheese defects can be correlated using Next-generation sequencing and high-performance liquid ...


Structure–Activity Relationship-Based Chemical Classification Of Highly Imbalanced Tox21 Datasets, Gabriel Idakwo, Sundar Thangapandian, Joseph Luttrell, Yan Li, Nan Wang, Zhaoxian Zhou, Huixiao Hong, Bei Yang, Chaoyang Zhang, Ping Gong 2020 University of Southern Mississippi

Structure–Activity Relationship-Based Chemical Classification Of Highly Imbalanced Tox21 Datasets, Gabriel Idakwo, Sundar Thangapandian, Joseph Luttrell, Yan Li, Nan Wang, Zhaoxian Zhou, Huixiao Hong, Bei Yang, Chaoyang Zhang, Ping Gong

Faculty Publications

The specificity of toxicant-target biomolecule interactions lends to the very imbalanced nature of many toxicity datasets, causing poor performance in Structure–Activity Relationship (SAR)-based chemical classification. Undersampling and oversampling are representative techniques for handling such an imbalance challenge. However, removing inactive chemical compound instances from the majority class using an undersampling technique can result in information loss, whereas increasing active toxicant instances in the minority class by interpolation tends to introduce artificial minority instances that often cross into the majority class space, giving rise to class overlapping and a higher false prediction rate. In this study, in order to ...


Genomics Education Partnership F Element Annotation Report, Amanda Moy 2020 Grand Valley State University

Genomics Education Partnership F Element Annotation Report, Amanda Moy

Honors Projects

The Genomics Education Partnership (GEP), headquartered at the University of Alabama, is a collection of over 100 universities that provide training and resources in order to provide students experiential learning in bioinformatics and genomics. The GEP hosts numerous research projects, including the F element project. The F element project has the main focus of annotating the F element genes of the fruit fly species D. ananassae, D. bipectinata, D. kikkawai, and D. takahashii. The Muller F element is the smallest chromosome in Drosophila species. However, the four species listed above have a notably larger F element than other Drosophila species ...


Gene Set Testing By Distance Correlation, Sho-Hsien Su 2020 University of Arkansas, Fayetteville

Gene Set Testing By Distance Correlation, Sho-Hsien Su

Theses and Dissertations

Pathways are the functional building blocks of complex diseases such as cancers. Pathway-level studies may provide insights on some important biological processes. Gene set test is an important tool to study the differential expression of a gene set between two groups, e.g., cancer vs normal. The differential expression of a gene set could be due to the difference in mean, variability, or both. However, most existing gene set tests only target the mean difference but overlook other types of differential expression. In this thesis, we propose to use the recently developed distance correlation for gene set testing. To assess ...


Ixodes Scapularis Src Kinase Is Required For Rickettsial Pathogen Survival In Ticks, Jeremy W. Turck 2020 Old Dominion University

Ixodes Scapularis Src Kinase Is Required For Rickettsial Pathogen Survival In Ticks, Jeremy W. Turck

Biological Sciences Theses & Dissertations

Anaplasma phagocytophilum is an obligate intracellular bacterium that causes disease in humans and animals. It is the causative agent for human anaplasmosis. A. phagocytophilum uses certain strategies to infect both vertebrates and invertebrates. It uses Ixodes scapularis ticks as a vector for spreading infection to other mammal species. This bacterium has a specific path for infection through the salivary glands of its vector host. It also suppresses certain functions such as the inhibition of apoptosis and ROS production in order to increase its survival in ticks. Src kinase, a non-receptor protein-tyrosine kinase, is a major player in cell signaling. Src ...


Investigation Of Sulfur Cycling In Marine Sponge Cinachyrella Spp. From A South Florida Reef, Shelby K. Cain 2020 Nova Southeastern University

Investigation Of Sulfur Cycling In Marine Sponge Cinachyrella Spp. From A South Florida Reef, Shelby K. Cain

All HCAS Student Capstones, Theses, and Dissertations

Symbionts within marine sponges are actively participating in the biogeochemical cycles. Among them, the role of symbiont microbes in the sulfur cycle remains a mystery. This study measured the abundance of microbes within the genus Cinachyrella before and after exposure to hydrogen sulfide. A four-part study was conducted: a) five-hour drop experiments, b) vertical distribution experiments, c) five-hour uptake experiments, and d) long-term exposure experiments. The five-hour drop experiment utilized a microsensor to measure sulfide levels, which was lowered 1.0 mm every thirty minutes for a total of 5 hours. Three trials were performed, each with one sponge and ...


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