Real-World Evaluation Of Universal Germline Screening For Cancer Treatment-Relevant Pharmacogenes, 2021 University of Kentucky
Real-World Evaluation Of Universal Germline Screening For Cancer Treatment-Relevant Pharmacogenes, Megan L. Hutchcraft, Nan Lin, Shulin Zhang, Catherine Sears, Kyle Zacholski, Elizabeth A. Belcher, Eric B. Durbin, John L. Villano, Michael J. Cavnar, Susanne M. Arnold, Frederick R. Ueland, Jill M. Kolesar
Pathology and Laboratory Medicine Faculty Publications
The purpose of this study was to determine the frequency of clinically actionable treatment-relevant germline pharmacogenomic variants in patients with cancer and assess the real-world clinical utility of universal screening using whole-exome sequencing in this population. Cancer patients underwent research-grade germline whole-exome sequencing as a component of sequencing for somatic variants. Analysis in a clinical bioinformatics pipeline identified clinically actionable pharmacogenomic variants. Clinical Pharmacogenetics Implementation Consortium guidelines defined clinical actionability. We assessed clinical utility by reviewing electronic health records to determine the frequency of patients receiving pharmacogenomically actionable anti-cancer agents and associated outcomes. This observational study evaluated 291 patients with ...
Random Forest-Integrated Analysis In Ad And Late Brain Transcriptome-Wide Data To Identify Disease-Specific Gene Expression, Xinxing Wu, Chong Peng, Peter T. Nelson, Qiang Cheng
Sanders-Brown Center on Aging Faculty Publications
Alzheimer's disease (AD) is a complex neurodegenerative disorder that affects thinking, memory, and behavior. Limbic-predominant age-related TDP-43 encephalopathy (LATE) is a recently identified common neurodegenerative disease that mimics the clinical symptoms of AD. The development of drugs to prevent or treat these neurodegenerative diseases has been slow, partly because the genes associated with these diseases are incompletely understood. A notable hindrance from data analysis perspective is that, usually, the clinical samples for patients and controls are highly imbalanced, thus rendering it challenging to apply most existing machine learning algorithms to directly analyze such datasets. Meeting this data analysis challenge ...
Phenotype Bias Determines How Natural Rna Structures Occupy The Morphospace Of All Possible Shapes, 2021 Gulf University for Science and Technology, Kuwait
Phenotype Bias Determines How Natural Rna Structures Occupy The Morphospace Of All Possible Shapes, Fatme Ghaddar, Dr Kamaludin Dingle, Dr Petr Sulc, Prof Ard A. Louis
Undergraduate Research Symposium
The relative prominence of developmental bias versus natural selection is a long standing controversy in evolutionary biology. Here we demonstrate quantitatively that developmental bias is the primary explanation for the occupation of the morphospace of RNA secondary structure (SS) shapes. By using the RNAshapes method to define coarse-grained SS classes, we can measure the frequencies that non-coding RNA SS shapes appear in nature. Our main findings are firstly that only the most frequent structures appear in nature; the vast majority of possible structures in the morphospace have not yet been explored. Secondly, and perhaps more surprisingly, these frequencies are accurately ...
Don't Sell Them Short, There's More To Bacterial Natural Products Than Antibiotics, 2021 The Graduate Center, City University of New York
Don't Sell Them Short, There's More To Bacterial Natural Products Than Antibiotics, Alison Clare Domzalski
Dissertations, Theses, and Capstone Projects
Recent genomic studies of microbiomes have revealed an overwhelming number of biosynthetic genes of unknown function. Most of these “cryptic” biosynthetic genes are not expressed in laboratory monocultures of individual microbes. Thus, there remains tremendous untapped potential for natural products discovery. Here we employ mixed microbial culture (MMC) as a simple yet powerful approach to awaken cryptic biosynthetic gene clusters. Our preliminary studies demonstrated that arrays of metabolites could be induced in MMCs upon environmental cues, such as surface adhesion. Using this system, we have screened, identified, and isolated bioactive bacterial metabolites, which were characterized structurally and biologically. Of the ...
In Silico Identification Of A Streptococcus Phage From An Unpasteurized Dairy Product, 2021 Kennesaw State University
In Silico Identification Of A Streptococcus Phage From An Unpasteurized Dairy Product
Symposium of Student Scholars
This study aimed to identify novel phages from a West African dairy product, nunu, to better understand the uncharacterized virosphere of a food microbiome. Nunu is a yogurt-like product from spontaneous fermentation of unpasteurized cow milk without a standardized starter culture. Phages and their bacterial hosts make up a microbiome, where their collective metagenome can be studied in silico, or computationally, after next generation sequencing (NGS). The targeted dataset for our study can be found in the Sequence Read Archives under the accession number of ERX2041567. This study utilized several bioinformatics software tools with customized settings: Kraken2, MetaVelvet, Edena, NCBI-BLAST ...
In Silico Isolation Of A Novel Phage For Food Safety Applications Against Pathogenic E. Coli, 2021 Kennesaw State University
In Silico Isolation Of A Novel Phage For Food Safety Applications Against Pathogenic E. Coli, Daisy Mcgrath
Symposium of Student Scholars
With the advent of next-generation sequencing (NGS) on metagenomes, the elucidation of all genetic material from microbiomes has prompted a renewed interest towards uncultivated members of the virosphere. We describe the discovery of a novel phage from a metagenomic dataset on the West African fermented dairy product, nunu, with a custom bioinformatics workflow to potentially serve as a biocontrol agent against pathogenic E. coli. Initial dataset of ERR2014814 from NCBI was first subjected to Kraken2 to extract novel sequencing reads for further de novo assembly into contigs by MetaVelvet. Resultant contigs served as potential partial phage genomes, then searched against ...
The Evolutionary Origins Of Autism Associated Genes And Their Role In Great Ape Socio-Communication, 2021 Kennesaw State University
The Evolutionary Origins Of Autism Associated Genes And Their Role In Great Ape Socio-Communication, Azeeza Abdulrauf, Martin Hudson, Susan M.E. Smith, Jared P. Taglialatela
Symposium of Student Scholars
Single nucleotide polymorphisms (SNPs) play a major role in socio-communicative behavior. For this study, the focus is on autism associated OXTR, AVPR1A, and FOXP2 SNPs, and the role they play in great apes. Prior research on the OXTR, AVPR1A, and FOXP2 SNPs show that they affect behavior skills such as understanding and controlling emotion, understanding the emotions of others, and communications skills. Great apes, such as bonobos, chimpanzees, and gorillas are the model, since they are our closest relatives in the animal kingdom capable of understanding complex communication. Each gene has at least two SNPS that are investigated in the ...
Insights Into Halophilic Microbial Adaptation: Analysis Of Integrons And Associated Genomic Structures And Characterization Of A Nitrilase In Hypersaline Environments, 2021 American University in Cairo
Insights Into Halophilic Microbial Adaptation: Analysis Of Integrons And Associated Genomic Structures And Characterization Of A Nitrilase In Hypersaline Environments, Sarah Sonbol
Theses and Dissertations
Hypersaline environments are extreme habitats that can be exploited as biotechnological resources. Here, we characterized a nitrilase (NitraS-ATII) isolated from Atlantis II Deep brine pool. It showed higher thermal stability and heavy metal tolerance compared to a closely related nitrilase.
We also studied integrons in halophiles and hypersaline environments. Integrons are genetic platforms in which an integron integrase (IntI) mediates the excision and integration of gene cassettes at specific recombination sites. In order to search for integrons in halophiles and hypersaline metagenomes, we used a PCR-based approach, in addition to different bioinformatics tools, mainly IntegronFinder.
We found that integrons and ...
Sciviewer Enables Interactive Visual Interrogation Of Single-Cell Rna-Seq Data From The Python Programming Environment [Preprint], 2021 Massachusetts Institute of Technology
Sciviewer Enables Interactive Visual Interrogation Of Single-Cell Rna-Seq Data From The Python Programming Environment [Preprint], Dylan Kotliar, Andres Colubri
University of Massachusetts Medical School Faculty Publications
Visualizing two-dimensional (2D) embeddings (e.g. UMAP or tSNE) is a key step in interrogating single-cell RNA sequencing (scRNA-Seq) data. Subsequently, users typically iterate between programmatic analyses (e.g. clustering and differential expression) and visual exploration (e.g. coloring cells by interesting features) to uncover biological signals in the data. Interactive tools exist to facilitate visual exploration of embeddings such as performing differential expression on user-selected cells. However, the practical utility of these tools is limited because they don’t support rapid movement of data and results to and from the programming environments where the bulk of data analysis takes ...
Bayesian Statistical Modeling Of Metagenomics Sequencing Data, 2021 Southern Methodist University
Bayesian Statistical Modeling Of Metagenomics Sequencing Data, Shuang Jiang
Statistical Science Theses and Dissertations
Microbiome count data are high-dimensional and usually suffer from uneven sampling depth, over-dispersion, and zero-inflation. In this thesis, we develop specialized analytical models for analyzing such count data. In Chapter 2, I develop a bi-level Bayesian hierarchical framework for microbiome differential abundance analysis. The bottom level is a multivariate count-generating process that links the observed counts to their latent normalized abundances. The top level is a mixture of Gaussian distributions with a feature selection scheme for differential abundance analysis. A simulation study on both simulated and synthetic data is conducted. A colorectal cancer case study demonstrates that a resulting diagnostic ...
Characterization Of The Growth Factor Receptor Network Oncogenes In Lung Cancer, 2021 Chapman University
Characterization Of The Growth Factor Receptor Network Oncogenes In Lung Cancer, Ashley Duche
Pharmaceutical Sciences (MS) Theses
Lung cancer remains the leading cause of cancer related deaths worldwide, reportedly contributing to 1.8 million of the 10.0 million mortalities documented in the year 2020. Although advancements have been made in therapeutics and diagnostic methods, formulation of effective treatments and development of drug resistance continues to be a challenge. These challenges arise from our lack of understanding of intricate signaling pathways, such as the Growth Factor Receptor Network (GFRN), which contributes to complex lung tumor heterogeneity allowing for drug resistance development. In this study, gene expression signatures of six GFRN oncogenes overexpressed in human mammary epithelial cells ...
Investigation Into The Evolution Of Heterogeneity Within Secondary Replicons And Their Maintenance In Genus Variovorax, 2021 California State University - San Bernardino
Investigation Into The Evolution Of Heterogeneity Within Secondary Replicons And Their Maintenance In Genus Variovorax, Christopher Ne Ville
Electronic Theses, Projects, and Dissertations
Approximately 10% of all bacterial genomes sequenced thus far contain a secondary replicon. This considerable genetic reservoir contains many potentially mobilizable elements, allowing for the formation of many unique secondary replicons. This property of bacterial populations vastly increases the genomic diversity available to species that effectively take up and maintain these replicons. Members of the genus Variovorax have extensive heterogeneity in genome architecture, including sequenced isolates containing plasmids, megaplasmids, and chromids. Using available Illumina data on the NCBI database, we have completed these assemblies using 3rd generation sequencing methods on 17 members of this genus. We have sequenced, assembled ...
Drug Repurposing For Covid-19 Using Molecular Docking Tools, 2021 Chapman University
Drug Repurposing For Covid-19 Using Molecular Docking Tools, Deniz Yasar Oztas
Computational and Data Sciences (MS) Theses
Since severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly contagious and mortal, finding a treatment is time critical. Drug repurposing is probably the quickest and safest approach in our arsenal. However, testing every drug in a brute force manner would require a lot of resources, and a more sophisticated method is required to filter possible candidates. Since several molecules have already been shown to be effective against SARS-CoV-2 in wet-lab experiments, choosing drugs with similar characteristics would increase our chances of success. In this study, we compare the molecular docking results of FDA-approved drugs from the ZINC database against ...
Using Bioenergetics To Model The Effects Of Climate Change On Bluntnose Minnows Pimephales Notatus In A Western Kentucky Stream, Christian Slone, Christian Slone
Student Scholarship & Creative Works
Bioenergetics considers a variety of factors like consumption, excretion, and metabolism to quantify the energy use of an organism. A common use of bioenergetics modeling is to help solve fish stock problems. This project looks to develop a bioenergetics model for Bluntnose Minnows Pimephales notatus to help predict effects of climate change on the biodiversity of western Kentucky streams. We used R and NetLogo to create an agent-based bioenergetics model to simulate the size distribution of Bluntnose Minnows under various temperature regimes. Bluntnose Minnow metabolism increases, and consumption decreases with an increase in water temperature. Fish growth seems to be ...
Beyond Safe Harbor: Risk Of Exposing Location In De-Identified Clinical Data, 2021 University of Nebraska Medical Center
Beyond Safe Harbor: Risk Of Exposing Location In De-Identified Clinical Data, Alfred J. Anzalone, Carol Reynolds Geary, James C. Mcclay
Posters and Presentations: Neurological Sciences
The use of de-identified EHR data for clinical and translational research has increased significantly since the HIPAA Privacy Rule De-Identification standards went into effect -Inclusion of SDOH measures in de-identified research is increasing as well, which presents an inherent risk of re-identifying PHI (primarily location units smaller than the state) -Data warehouse architecture and institutional policies need to recognize the risk associated with providing multiple location-based indices -Research interests are secondary to privacy concerns throughout biomedical research, but particularly in de-identified research, which is intended to promote more secure access to EHR data while allowing for expedient access (fewer institutional ...
Human Apobec3 Variations And Viral Infection, 2021 University of California, Irvine
Human Apobec3 Variations And Viral Infection, Shiva Sadeghpour, Saeideh Khodaee, Mostafa Rahnama, Hamzeh Rahimi, Diako Ebrahimi
Plant Pathology Faculty Publications
Human APOBEC3 (apolipoprotein B mRNA-editing catalytic polypeptide-like 3) enzymes are capable of inhibiting a wide range of endogenous and exogenous viruses using deaminase and deaminase-independent mechanisms. These enzymes are essential components of our innate immune system, as evidenced by (a) their strong positive selection and expansion in primates, (b) the evolution of viral counter-defense mechanisms, such as proteasomal degradation mediated by HIV Vif, and (c) hypermutation and inactivation of a large number of integrated HIV-1 proviruses. Numerous APOBEC3 single nucleotide polymorphisms, haplotypes, and splice variants have been identified in humans. Several of these variants have been reported to be associated ...
Graph-Theoretic Partitioning Of Rnas And Classification Of Pseudoknots-Ii, 2021 CUNY College of Staten Island
Graph-Theoretic Partitioning Of Rnas And Classification Of Pseudoknots-Ii, Louis Petingi
Publications and Research
Dual graphs have been applied to model RNA secondary structures with pseudoknots, or intertwined base pairs. In previous works, a linear-time algorithm was introduced to partition dual graphs into maximally connected components called blocks and determine whether each block contains a pseudoknot or not. As pseudoknots can not be contained into two different blocks, this characterization allow us to efficiently isolate smaller RNA fragments and classify them as pseudoknotted or pseudoknot-free regions, while keeping these sub-structures intact. Moreover we have extended the partitioning algorithm by classifying a pseudoknot as either recursive or non-recursive in order to continue with our research ...
Demonstrating An Approach For Evaluating Synthetic Geospatial And Temporal Epidemiologic Data Utility: Results From Analyzing >1.8 Million Sars-Cov-2 Tests In The United States National Covid Cohort Collaborative (N3c) [Preprint], 2021 University of Washington
Demonstrating An Approach For Evaluating Synthetic Geospatial And Temporal Epidemiologic Data Utility: Results From Analyzing >1.8 Million Sars-Cov-2 Tests In The United States National Covid Cohort Collaborative (N3c) [Preprint], Jason A. Thomas, Randi E. Foraker, Noa Zamstein, Philip R.O. Payne, Adam B. Wilcox
UMass Center for Clinical and Translational Science Supported Publications
Objective To evaluate whether synthetic data derived from a national COVID-19 data set could be used for geospatial and temporal epidemic analyses.
Materials and Methods Using an original data set (n=1,854,968 SARS-CoV-2 tests) and its synthetic derivative, we compared key indicators of COVID-19 community spread through analysis of aggregate and zip-code level epidemic curves, patient characteristics and outcomes, distribution of tests by zip code, and indicator counts stratified by month and zip code. Similarity between the data was statistically and qualitatively evaluated.
Results In general, synthetic data closely matched original data for epidemic curves, patient characteristics, and ...
Biol 4010w/7190g/Cisc2810w: Macromolecular Structure And Bioinformatics, 2021 CUNY Brooklyn College
Biol 4010w/7190g/Cisc2810w: Macromolecular Structure And Bioinformatics, Shaneen Singh
Open Educational Resources
No abstract provided.
The Differences Of Prokaryotic Pan-Genome Analysis On Complete Genomes And Simulated Metagenome-Assembled Genomes, 2021 University of Nebraska-Lincoln
The Differences Of Prokaryotic Pan-Genome Analysis On Complete Genomes And Simulated Metagenome-Assembled Genomes, Tang Li
Dissertations, Theses, & Student Research in Food Science and Technology
Metagenomic assembly is often used in microbiome research. In metagenomic assembly, contigs are binned based on the shared nucleotide composition. These contig bins are called metagenome-assembled genomes (MAGs), each representing a unique bacterial genome recovered from metagenome sequencing. Hundreds of thousands of high-quality MAGs of various ecological environments have been published since 2017, and increasingly more MAGs are being used in pan-genome analyses where unculturable species or species without reference genomes are studied in microbiome research. However, compared to the traditional pan-genome analysis that uses isolate genomes (from a pure strain isolated from a mixed bacterial population), it is not ...