Genetics and Genomics Commons^™

Minimal Positional Substring Cover Is A Haplotype Threading Alternative To Li And Stephens Model, Ahsan Sanaullah, Degui Zhi, Shaojie Zhang

Faculty, Staff and Student Publications

The Li and Stephens (LS) hidden Markov model (HMM) models the process of reconstructing a haplotype as a mosaic copy of haplotypes in a reference panel. For small panels, the probabilistic parameterization of LS enables modeling the uncertainties of such mosaics. However, LS becomes inefficient when sample size is large, because of its linear time complexity. Recently the PBWT, an efficient data structure capturing the local haplotype matching among haplotypes, was proposed to offer a fast method for giving some optimal solution (Viterbi) to the LS HMM. Previously, we introduced the minimal positional substring cover (MPSC) problem as an alternative …

Atomistic Assessment Of Drug-Phospholipid Interactions Consequent To Cancer Treatment: A Study Of Anthracycline Cardiotoxicity, Yara Elsayed Ahmed

Theses and Dissertations

Despite being one of the most effective chemotherapeutic agents developed to date, Anthracyclines are notorious for their cardiotoxicity. Their clinical use is frequently limited both in dosage and in prescription due to the severe cardiac damage they cause. The mechanism of anthracycline-induced cardiotoxicity is not yet fully understood. However, it is hypothesized that interactions with the myocardial membrane play an important role in imparting cardiotoxicity. In this study, we use molecular dynamics simulations and density functional theory calculations to study the anthracycline drug molecules and the interactions that they have with the myocardial membrane. We construct a myocardial membrane model …

The Integrative Studies On The Functional A-To-I Rna Editing Events In Human Cancers, Sijia Wu, Zhiwei Fan, Pora Kim, Liyu Huang, Xiaobo Zhou

Faculty, Staff and Student Publications

Adenosine-to-inosine (A-to-I) RNA editing, constituting nearly 90% of all RNA editing events in humans, has been reported to contribute to the tumorigenesis in diverse cancers. However, the comprehensive map for functional A-to-I RNA editing events in cancers is still insufficient. To fill this gap, we systematically and intensively analyzed multiple tumorigenic mechanisms of A-to-I RNA editing events in samples across 33 cancer types from The Cancer Genome Atlas. For individual candidate among ∼ 1,500,000 quantified RNA editing events, we performed diverse types of downstream functional annotations. Finally, we identified 24,236 potentially functional A-to-I RNA editing events, including the cases …

Machine Learning And Network Embedding Methods For Gene Co-Expression Networks, Niloofar Aghaieabiane

Dissertations

High-throughput technologies such as DNA microarrays and RNA-seq are used to measure the expression levels of large numbers of genes simultaneously. To support the extraction of biological knowledge, individual gene expression levels are transformed into Gene Co-expression Networks (GCNs). GCNs are analyzed to discover gene modules. GCN construction and analysis is a well-studied topic, for nearly two decades. While new types of sequencing and the corresponding data are now available, the software package WGCNA and its most recent variants are still widely used, contributing to biological discovery.

The discovery of biologically significant modules of genes from raw expression data is …

Du Undergraduate Showcase: Research, Scholarship, And Creative Works, Caitlyn Aldersea, Justin Bravo, Sam Allen, Anna Block, Connor Block, Emma Buechler, Maria De Los Angeles Bustillos, Arianna Carlson, William Christensen, Olivia Kachulis, Noah Craver, Kate Dillon, Muskan Fatima, Angel Fernandes, Emma Finch, Colleen Cassidy, Amy Fishman, Andrea Francis, Stacia Fritz, Simran Gill, Emma Gries, Rylie Hansen, Shannon Powers, Jacqueline Martinez, Zachary Harker, Ashley Hasty, Mykaela Tanino-Springsteen, Kathleen Hopps, Adelaide Kerenick, Colin Kleckner, Ci Koehring, Elijah Kruger, Braden Krumholz, Maddie Leake, Lyneé Alves, Seraphina Loukas, Yatzari Lozano Vazquez, Haley Maki, Emily Martinez, Sierra Mckinney, Audrey Mitchell, Kipling Newman, Audrey Ng, Megan Lucyshyn, Andrew Nguyen, Stevie Ostman, Casandra Pearson, Alexandra Penney, Julia Gielczynski, Tyler Ball, Anna Rini, Christina Rorres, Simon Ruland, Helayna Schafer, Emma Sellers, Sarah Schuller, Claire Shaver, Kevin Summers, Isabella Shaw, Madison Sinar, Claudia Pena, Apshara Siwakoti, Carter Sorensen, Madi Sousa, Anna Sparling, Alexandra Revier, Brandon Thierry, Dylan Tyree, Maggie Williams, Lauren Wols

DU Undergraduate Research Journal Archive

DU Undergraduate Showcase: Research, Scholarship, and Creative Works

Development Of Three Novel Edna Assays For Detecting Coastal Sharks, Kristina Dawn Flanigan

Electronic Theses and Dissertations

Environmental DNA (eDNA) analysis is an emerging, non-invasive community monitoring tool. This study aimed to determine if eDNA methods can be reliably used in a large brackish, partially mixed estuary by developing and testing three novel eDNA primers, for Sandbar Sharks (Carcharhinus plumbeus), Blacknose Sharks (Carcharhinus acronotus), and Bonnetheads (Sphyrna tiburo). These primers were designed to target 109, 156, and 120 base pair (bp) fragments, respectively, of the highly conserved NAD2 gene in the mitochondrial genome of each species. Primer function was validated through testing against 102 known genomic source samples and 25 filtered water samples from aquaria in which …

Spatial Metabolomics Reveals Glycogen As An Actionable Target For Pulmonary Fibrosis, Lindsey R. Conroy, Harrison A. Clarke, Derek B. Allison, Samuel Santos Valenca, Qi Sun, Tara R. Hawkinson, Lyndsay E. A. Young, Juanita E. Ferreira, Autumn V. Hammonds, Jaclyn B. Dunne, Robert J. Mcdonald, Kimberly J. Absher, Brittany Dong, Ronald C. Bruntz, Kia H. Markussen, Jelena A. Juras, Warren J. Alilain, Jinze Liu, Matthew S. Gentry, Peggi M. Angel, Christopher M. Waters, Ramon C. Sun

Saha Cardiovascular Research Center Faculty Publications

Matrix assisted laser desorption/ionization imaging has greatly improved our understanding of spatial biology, however a robust bioinformatic pipeline for data analysis is lacking. Here, we demonstrate the application of high- dimensionality reduction/spatial clustering and histopathological annotation of matrix assisted laser desorption/ionization imaging datasets to assess tissue metabolic heterogeneity in human lung diseases. Using metabolic features identified from this pipeline, we hypothesize that metabolic channeling between glycogen and N-linked glycans is a critical metabolic process favoring pulmonary fibrosis progression. To test our hypothesis, we induced pulmonary fibrosis in two different mouse models with lysosomal glycogen utilization deficiency. Both mouse models displayed …

Deephtlv: A Deep Learning Framework For Detecting Human T-Lymphotrophic Virus 1 Integration Sites, Johnathan Jia, Johnathan Jia

Dissertations and Theses (Open Access)

In the 1980s, researchers found the first human oncogenic retrovirus called human T-lymphotrophic virus type 1 (HTLV-1). Since then, HTLV-1 has been identified as the causative agent behind several diseases such as adult T-cell leukemia/lymphoma (ATL) and a HTLV-1 associated myelopathy or tropical spastic paraparesis (HAM/TSP). As part of its normal replication cycle, the genome is converted into DNA and integrated into the genome. With several hundreds to thousands of unique viral integration sites (VISs) distributed with indeterminate preference throughout the genome, detection of HTLV-1 VISs is a challenging task. Experimental studies typically use molecular biology …

Physio-Psycho-Social Interaction Mechanism In Dyadic Health Of Young And Middle-Aged Stroke Survivors And Their Spousal Caregivers: A Longitudinal Observational Study Protocol, Dandan Xiang, Zhen-Xiang Zhang, Song Ge, Wen Na Wang, Bei-Lei Lin, Su-Yan Chen, Er-Feng Guo, Peng-Bo Zhang, Zhi-Wei Liu, Hui Li, Yong-Xia Mei

Faculty, Staff and Student Publications

Introduction: In recent years, stroke has become more common among young people. Stroke not only has a profound impact on patients' health but also incurs stress and health threats to their caregivers, especially spousal caregivers. Moreover, the health of stroke survivors and their caregivers is interdependent. To our knowledge, no study has explored dyadic health of young and middle-aged stroke survivors and their spousal caregivers from physiological, psychological and social perspectives. Therefore, this proposed study aims to explore the mechanism of how physiological, psychological and social factors affect dyadic health of young and middle-aged stroke survivors and their spousal caregivers. …

Physiological And Transcriptomic Responses Of Two Artemisia Californica Populations To Drought: Implications For Restoring Drought-Resilient Native Communities, Hagop S. Atamian Dr., Jennifer L. Funk

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

As climate change brings drier and more variable rainfall patterns to many arid and semi-arid regions, land managers must re-assemble appropriate plant communities for these conditions. Transcriptome sequencing can elucidate the molecular mechanisms underlying plant responses to changing environmental conditions, potentially enhancing our ability to screen suitable genotypes and species for restoration. We examined physiological and morphological traits and transcriptome sequences of coastal and inland populations of California sagebrush (Artemisia californica), a critical shrub used to restore coastal sage scrub vegetation communities, grown under low and high rainfall environments. The populations are located approximately 36 km apart but …

Effect Of Varied Macronutrient Ratios On Honey Bee Tolerance To Iapv Infection, Caitlin Lennon-Puthoff, Alex Payne, Adam Dolezal

PRECS student projects

Honey bees are killed by Israeli acute paralysis virus (IAPV). Because this virus has no cure, it is important to lessen its impact on bees through proper nutrition. This project explores the effects of differing protein to lipid (P:L) ratios in pollen on honey bee susceptibility to this virus.

Over three trials, bees in cages were incubated for 3 days to resemble hive conditions. Two doses of IAPV (10^-3 & 10^-2) and a negative control were used, along with five P:L ratios (1.5, 2.5, 11.5, 16.5, & 21.5:1) and a sucrose-only diet. These treatment groups were combined …

Evaluating The Enzymatic Activity Of Transformed X. Cucurbitae, Emily Beger, Iris Lee, Sarah Hind

PRECS student projects

Introduction

• The United States’ pumpkin industry exceeds one billion dollars [1], with Illinois contributing to over 90% of processing pumpkin production.
• Pumpkin growers face a rising concern due to the increasing occurrence of Xanthomonas cucurbitae , the pathogen that causes bacterial spot disease in cucurbits, including pumpkins.
• X. cucurbitae infection leads to the appearance of small, sunken, beige spots on cucurbit fruits and leaves.
• Over time, the bacterium can compromise fruit integrity by breaking down the epidermis and cuticle. • Bacterial spot disease also creates opportunities for other bacteria and fungi to infiltrate the affected fruits, leading to fruit rot …

Identifying Genes Influencing The Efficiency Of Photosynthesis, Jason M. Rivera, Steven Burgess

PRECS student projects

• Photosynthesis adapts to environmental conditions over time.¹

• Varying environmental conditions lead to stress accumulation on the plant.²

• A genetic library has been assembled for forward genetic screening of Arabidopsis thaliana.³

• Arabidopsis Thaliana is a model plant used as a model organism in growth experiments.

• This research project aims to identify and analyze candidate genes that impact the efficiency of photosynthesis.

• These genes can be transplanted into commercial crops to increase efficiency of photosynthesis and crop yields.

Confirming Presence And Mobilization Of Partner Quality Genes In Sinorhizobium Meliloti, Ethan Perez, Ivan Sosa Marquez, Katy Heath

PRECS student projects

• Mutualism is an interaction in which two organisms benefit from each other.
• The symbiotic relationship between the bacterium Sinorhizobium meliloti and the plant Medicago truncatula is dictated by the bacterial plasmids.
• The Heath lab has a collection of 191 Sinorhizobium meliloti strains with different symbiotic plasmids that vary across populations (Riley et al., 2022).
• Each strain can be a better or worse partner for its plant host in symbiosis with the variation in fitness being called partner quality (Fig. 1)
• These traits can be traced back to the genetic elements that underlie this effect (Batstone et al.,
• These genetic elements …

Fusarium Isolates Adapt To Specific Wheat Tissues, Liam Kent, Mara Krone, Santiago Mideros

PRECS student projects

Introduction

Tissue specificity is a pathogen’s preference for infecting one section of tissue (i.e., root, stem, or head) over another. 1 Having a better understanding of a pathogen’s ability to cause disease on specific tissues could contribute to new mechanisms of disease control. This will allow growers to make the best decision on effective pathogen management. In 2022, Fusarium isolates were collected from wheat heads and roots across Illinois. These isolates were used in a pathogen aggressiveness assay on wheat roots, in an in vitro growth rate experiment , and in the development of a spore quantification protocol. The phenotypic …

Role Of Age And Sex In The Effects Of Repeated Methamphetamine Exposure On Hedonic Tone In Sprague Dawley Rats, Cameron Lewis, Conor Strumberger, Joshua M. Gulley

PRECS student projects

Anhedonia is defined as a reduced or complete loss of pleasure from a previously pleasurable stimulus, and it is comprised of two dimensions:

• Hedonic anhedonia consists of a distinct loss of pleasure in consumption of a normally pleasurable stimulus.
• Motivational anhedonia involves the goal directed behavior to obtain a reward.

Withdrawal induced anhedonia following use of methamphetamine (METH) is thought to contribute to relapse behaviors^1,2 . The anhedonic effects of drug withdrawal largely depend on dose, frequency, and the duration of drug exposure^4,5,6.

The role of sex and age of exposure in this context has yet to …

Acth Challenge: Stress Response Across Tadpole Development, Lauren W. Mobo, Lucas Jimenez, Lisa L. Surber-Cunningham, Eva K. Fischer

PRECS student projects

Research Questions

1. Do tadpoles excrete more cortisol or corticosterone?
2. Do tadpoles excrete more corticosterone after ACTH injections?
3. Does the ACTH stress response change across development?

The Tomato Strikes Back: Plant Response To Environmental Stress, Maya K. Davis, Erinn Dady, Esther N. Ngumbi

PRECS student projects

Introduction

• Tomato is an important vegetable. Its production is threatened due to altered weather patterns which increase environmental stressors such as flooding^{1, 2} and herbivory³ to crops.
• Plants respond in many ways. Stressed plants strike back to environmental stress by altering their chemistry⁴:

1. Volatile Organic Compounds (VOCs) emissions
2. Defensive secondary metabolites²

• Stress induced physiological changes in plants impact growth and development of insects.
• This study is broken into two experiments:

1. The plant response to flooding stress
2. The insect performance on flooded plants

Potential Implications Of Elevated Co2 For Enhanced Rock Weathering In Croplands, Hannah Maher, Megan Allen, Lisa Ainsworth

PRECS student projects

• Atmospheric carbon dioxide (CO₂) levels are increasing by 2.37 ppm year, and levels have increased from about 370 ppm in 2000 to about 420 ppm in 2023¹
• Increased CO₂ levels result in climate change, including increased temperatures and drought which impacts soybean crops
• Enhanced Rock Weathering (ERW) is the process of spreading basalt on fields to accelerate the natural reaction between rocks, CO2, and water²
• Enhanced Rock Weathering is a possible way to combat increasing CO₂ levels because of its carbon sequestration properties²

Revisiting The Reproductive Behaviors Of Blackspotted Stickleback, Cassidy Constant, Megan Tucker, Colby Behrens, Alison M. Bell

PRECS student projects

Why Blackspotted Stickleback?

How Behaviors Evolve Comparing closely related species can give insights into how behavior evolves.

Well studied: Three-spined Stickleback (Gasterosteus aculeatus)

• Model organism for natural variation in behavioral evolution 1.
• Divergence in parental care in two ecotypes1,2.
• White and common ecotypes recently diverged 2.

Lesser studied: Blackspotted Stickleback (Gasterosteus wheatlandi)

• Three-spined’s closest living relative.
• Possible behavioral intermediate of commons & whites.
• Blackspotted egg dispersal is similar to white three-spined 3.

How Fungicide Alters The Hidden Mycobiome Of A Restored Prairie System, Mya Reyes, Noah Brown, Anthony Yannarell

PRECS student projects

• Fungal Endophytes are microscopic fungi that live inside plant tissues and form a symbiotic relationship that influences the fitness of both parties.

• Fungicides are a widely used method of crop disease control in agriculture, but fungicides can be carried into other environments by water and wind.

• This experiment looks at how long-term fungicide exposure affects diversity of fungal endophytes that are grown in vitro as well as screens them for phosphate solubilization ability.

• Phosphate is a vital macronutrient that is essential for making nucleic acids (DNA, RNA) as well as playing a vital role in energy transfer throughout the plant's …

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In Situ Microwave Fixation Provides An Instantaneous Snapshot Of The Brain Metabolome, Jelena A. Juras, Madison B. Webb, Lyndsay E. A. Young, Kia H. Markussen, Tara R. Hawkinson, Michael D. Buoncristiani, Kayli E. Bolton, Peyton T. Coburn, Meredith I. Williams, Lisa P. Y. Sun, William C. Sanders, Ronald C. Bruntz, Lindsey R. Conroy, Chi Wang, Matthew S. Gentry, Bret N. Smith, Ramon C. Sun

Markey Cancer Center Faculty Publications

Brain glucose metabolism is highly heterogeneous among brain regions and continues postmortem. In particular, we demonstrate exhaustion of glycogen and glucose and an increase in lactate production during conventional rapid brain resection and preservation by liquid nitrogen. In contrast, we show that these post- mortem changes are not observed with simultaneous animal sacrifice and in situ fixation with focused, high- power microwave. We further employ microwave fixation to define brain glucose metabolism in the mouse model of streptozotocin-induced type 1 diabetes. Using both total pool and isotope tracing analyses, we identified global glucose hypometabolism in multiple brain regions, evidenced by …

Targeting Lncrna Ddit4-As1 Sensitizes Triple Negative Breast Cancer To Chemotherapy Via Suppressing Of Autophagy, Ting Jiang, Jiaojiao Zhu, Shilong Jiang, Zonglin Chen, Ping Xu, Rong Gong, Changxin Zhong, Yueying Cheng, Xinyuan Sun, Wenjun Yi, Jinming Yang, Wenhu Zhou, Yan Cheng

Markey Cancer Center Faculty Publications

In this study, it is found that the lncRNA, DNA damage inducible transcript 4 antisense RNA1 (DDIT4-AS1), is highly expressed in triple-negative breast cancer (TNBC) cell lines and tissues due to H3K27 acetylation in the promoter region, and promotes the proliferation, migration, and invasion of TNBC cells via activating autophagy. Mechanistically, it is shown that DDIT4-AS1 induces autophagy by stabilizing DDIT4 mRNA via recruiting the RNA binding protein AUF1 and promoting the interaction between DDIT4 mRNA and AUF1, thereby inhibiting mTOR signaling pathway. Furthermore, silencing of DDIT4-AS1 enhances the sensitivity of TNBC cells to chemotherapeutic agents such as paclitaxel both …

Margalefidinium Polykrikoides Cyst Resuspension In The Lafayette River, A Sub-Tributary Of The Chesapeake Bay, Gabrielle Greaney, Eduardo Perez Vega, Katherine Crider, Dreux Chappell, Kimberly Powell, Richard Hale, Peter Bernhardt, Margaret Mulholland

Undergraduate Research Symposium

Harmful Algal Blooms are a collection of algae in a body of water that can cause serious environmental issues and health problems in both people and aquatic organisms. Dinoflagellates are microscopic, unicellular, and eukaryotic organisms that are well known for forming harmful algal blooms because of eutrophication. Coastal Virginia suffers from HABs in the Chesapeake Bay and its tributaries. A common species of dinoflagellate, known as Margalefidinium polykrikoides exists in the Chesapeake Bay. The purpose of this study is to determine if sediment resuspension produced by wind generated surface gravity waves cause cysts (dinoflagellate resting stages) to be suspended into …

Intellectual Disability Related To De Novo Germline Loss Of The Distal End Of The P-Arm Of Chromosome 17: A Case Report, Eden Pope, Matthew Huertas, Amar Paul, Braden Cunningham, Matthew Jennings, Ryan Perry, Stephanie Chavez, John A. Kriak, Kyle B. Bills, David W. Sant

Annual Research Symposium

Hypothesis/Purpose: In this report we present a case of a 20-year-old female with congenital intellectual disability, stunted growth, and hypothyroidism. Competitive genetic hybridization (CHG) revealed a loss of 17p13.3, and the deletion was not present in either parent. This deletion has not previously been characterized, but mutations on the p-arm of chromosome 17 are responsible for Miller-Dieker Syndrome and Isolated Lissencephaly Sequence, both of which share symptoms in common with the patient.

Methods: Peripheral mononuclear cells (PBMCs) were used for karyotyping and competitive genetic hybridization (CHG). Bioinformatic analysis was carried out using the Genome Data Viewer (ncbi.nlm.nih.gov/genome/gdv).

Results: Karyotype was …

Presentation Of Paired P- And Q-Arm Mosaic Deletions On Chromosome 18 Associated With Neuropsychiatric Symptoms, Jackson Nielsen, Laura Minor, John Dougherty Jr., Paige Moore, Kailee Edwards, Brandon Burrell, Jameson Williams, John A. Kriak, David W. Sant, Kyle B. Bills

Annual Research Symposium

No abstract provided.

Clic And Membrane Wound Repair Pathways Enable Pandemic Norovirus Entry And Infection, B. Vijayalakshmi Ayyar, Khalil Ettayebi, Wilhelm Salmen, Umesh C. Karandikar, Frederick H. Neill, Victoria R. Tenge, Sue E. Crawford, Erhard Bieberich, B. V. Venkataram Prasad, Robert L. Atmar, Mary K. Estes

Markey Cancer Center Faculty Publications

Globally, most cases of gastroenteritis are caused by pandemic GII.4 human norovirus (HuNoV) strains with no approved therapies or vaccines available. The cellular pathways that these strains exploit for cell entry and internalization are unknown. Here, using nontransformed human jejunal enteroids (HIEs) that recapitulate the physiology of the gastrointestinal tract, we show that infectious GII.4 virions and virus-like particles are endocytosed using a unique combination of endosomal acidification-dependent clathrin-independent carriers (CLIC), acid sphingomyelinase (ASM)-mediated lysosomal exocytosis, and membrane wound repair pathways. We found that besides the known interaction of the viral capsid Protruding (P) domain with host glycans, the Shell …

A Computational Analysis Of Hybrid Genome Assembly Strategies, Joseph Walewski

Computer Science Honors Papers

The central dogma of molecular biology states that DNA is transcribed to RNA and then translated into proteins. Since DNA is the starting material for many of biology’s macromolecules, it has been referred to as “nature’s instruction book.” The sum of all DNA in a cell is referred to as the genome, and genome sequencing is how we interpret the DNA.

Due to limitations on currently available technology, it is not possible to retrieve the entire genome in one contiguous set of data. Therefore, genome sequencing is a computer science problem as sequencing “reads” must be stitched together to obtain …

Extracting High-Molecular Weight Dna From Cyanobacteria Using Promega's Wizard® Hmw Dna Extraction Kit With A Modified Protocol, Metis, Megan A. Hept, Lesley H. Greene

Chemistry & Biochemistry Faculty Publications

Extraction of high molecular weight (HMW) DNA for long read sequencing with little to no fragmentation and high purity is difficult to acquire from cyanobacterial species. Here we describe a modified method of extraction using Promega's Wizard® HMW DNA Extraction Kit to acquire high molecular weight DNA from cyanobacterial species. The protocol used in the kit is the “3.D. Isolating HMW DNA from Gram-Positive and Gram-Negative Bacteria” protocol. During a key step in the protocol, the lingering remnants of the mucilage layer of the cyanobacterial species is removed, preventing it from sticking to the DNA pellet produced. This customized modification …

Dfhic: A Dilated Full Convolution Model To Enhance The Resolution Of Hi-C Data, Bin Wang, Kun Liu, Yaohang Li, Jianxin Wang

Computer Science Faculty Publications

Motivation: Hi-C technology has been the most widely used chromosome conformation capture(3C) experiment that measures the frequency of all paired interactions in the entire genome, which is a powerful tool for studying the 3D structure of the genome. The fineness of the constructed genome structure depends on the resolution of Hi-C data. However, due to the fact that high-resolution Hi-C data require deep sequencing and thus high experimental cost, most available Hi-C data are in low-resolution. Hence, it is essential to enhance the quality of Hi-C data by developing the effective computational methods.

Results: In this work, we propose …