Digital Commons Network^™

Genome-Wide Methylation Patterns In Primary Uveal Melanoma: Development Of Methylsig-Um, An Epigenomic Prognostic Signature To Improve Patient Stratification, Emilie Lalonde, Dong Li, Kathryn Ewens, Carol L. Shields, Arupa Ganguly

Wills Eye Hospital Papers

Despite studies highlighting the prognostic utility of DNA methylation in primary uveal melanoma (pUM), it has not been translated into a clinically useful tool. We sought to define a methylation signature to identify newly diagnosed individuals at high risk for developing metastasis. Methylation profiling was performed on 41 patients with pUM with stage T2-T4 and at least three years of follow-up using the Illumina Infinium HumanMethylation450K BeadChip (N = 24) and the EPIC BeadChip (N = 17). Findings were validated in the TCGA cohort with known metastatic outcome (N = 69). Differentially methylated probes were identified in patients who developed …

Identification Of Immune-Associated Biomarkers Of Diabetes Nephropathy Tubulointerstitial Injury Based On Machine Learning: A Bioinformatics Multi-Chip Integrated Analysis, Lin Wang, Jiaming Su, Zhongjie Liu, Shaowei Ding, Yaotan Li, Baoluo Hou, Yuxin Hu, Zhaoxi Dong, Jingyi Tang, Hongfang Liu, Weijing Liu

Student and Faculty Publications

BACKGROUND: Diabetic nephropathy (DN) is a major microvascular complication of diabetes and has become the leading cause of end-stage renal disease worldwide. A considerable number of DN patients have experienced irreversible end-stage renal disease progression due to the inability to diagnose the disease early. Therefore, reliable biomarkers that are helpful for early diagnosis and treatment are identified. The migration of immune cells to the kidney is considered to be a key step in the progression of DN-related vascular injury. Therefore, finding markers in this process may be more helpful for the early diagnosis and progression prediction of DN.

METHODS: The …

Elucidating Immune-Related Gene Transcriptional Programs Via Factorization Of Large-Scale Rna-Profiles, Shan He, Matthew M Gubin, Hind Rafei, Rafet Basar, Merve Dede, Xianli Jiang, Qingnan Liang, Yukun Tan, Kunhee Kim, Maura L Gillison, Katayoun Rezvani, Weiyi Peng, Cara Haymaker, Sharia Hernandez, Luisa M Solis, Vakul Mohanty, Ken Chen

Student and Faculty Publications

Recent developments in immunotherapy, including immune checkpoint blockade (ICB) and adoptive cell therapy (ACT), have encountered challenges such as immune-related adverse events and resistance, especially in solid tumors. To advance the field, a deeper understanding of the molecular mechanisms behind treatment responses and resistance is essential. However, the lack of functionally characterized immune-related gene sets has limited data-driven immunological research. To address this gap, we adopted non-negative matrix factorization on 83 human bulk RNA sequencing (RNA-seq) datasets and constructed 28 immune-specific gene sets. After rigorous immunologist-led manual annotations and orthogonal validations across immunological contexts and functional omics data, we demonstrated …

Identification Of Circrna Biomarkers In Osteosarcoma: An Updated Systematic Review And Meta-Analysis, Chunbin Zhou, Lois Balmer, Manshu Song, Gehendra Mahara, Kezhou Wu, Wei Wang, Hu Wang

Research outputs 2022 to 2026

Circular RNAs (circRNAs) play a crucial role in cancer development and progression. This study aimed to identify potential circRNA biomarkers for osteosarcoma. Articles published from January 2010 to September 2023 were searched across eight databases to compare circRNA expression profiles in osteosarcoma and control samples (human, animal and cell lines). Meta-analysis was conducted under a random effects model. Subgroup analysis of circRNAs in different samples and tissues was performed. Diagnostic value was evaluated using receiver operator characteristic curves. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis explored functions of circRNA host genes. A circRNA-miRNA-mRNA axis …

A Bioinformatic Analysis Of T-Cell Epitope Diversity In Sars-Cov-2 Variants: Association With Covid-19 Clinical Severity In The United States Population, Grace J. Kim, Jacob H. Elnaggar, Mallory Varnado, Amy K. Feehan, Darlene Tauzier, Rebecca Rose, Susanna L. Lamers, Maya Sevalia, Najah Nicholas, Elizabeth Gravois, Daniel Fort, Judy S. Crabtree, Lucio Miele

School of Graduate Studies Faculty Publications

Long-term immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires the identification of T-cell epitopes affecting host immunogenicity. In this computational study, we explored the CD8+ epitope diversity estimated in 27 of the most common HLA-A and HLA-B alleles, representing most of the United States population. Analysis of 16 SARS-CoV-2 variants [B.1, Alpha (B.1.1.7), five Delta (AY.100, AY.25, AY.3, AY.3.1, AY.44), and nine Omicron (BA.1, BA.1.1, BA.2, BA.4, BA.5, BQ.1, BQ.1.1, XBB.1, XBB.1.5)] in analyzed MHC class I alleles revealed that SARS-CoV-2 CD8+ epitope conservation was estimated at 87.6%–96.5% in spike (S), 92.5%–99.6% in membrane (M), and 94.6%–99% in …

Creating Interpretable Deep Learning Models To Identify Species Using Environmental Dna Sequences, Samuel Waggoner

Honors College

This research aims to develop an interpretable and fast machine learning (ML) model for identifying species using environmental DNA (eDNA). eDNA is a technique used to detect the presence or absence of species in an ecosystem by analyzing the DNA that animals naturally leave behind in water or soil. However, there can be millions of sequences to classify and the reference databases are sizeable, so traditional methods such as BLAST are slow. Convolutional neural networks (CNNs) have been shown to be 150 times faster at classifying sequences. In this work, we create a CNN that achieves 92.5% accuracy, surpassing the …

An Investigation Of Information Structures In Dna, Joel Mohrmann

Department of Electrical and Computer Engineering: Dissertations, Theses, and Student Research

The information-containing nature of the DNA molecule has been long known and observed. One technique for quantifying the relationships existing within the information contained in DNA sequences is an entity from information theory known as the average mutual information (AMI) profile. This investigation sought to use principally the AMI profile along with a few other metrics to explore the structure of the information contained in DNA sequences.

Treating DNA sequences as an information source, several computational methods were employed to model their information structure. Maximum likelihood and maximum a posteriori estimators were used to predict missing bases in DNA sequences. …

Archaeal Diversity In The Anna's Hummingbird Microbiome, Lauren E. Chance

Honors Scholar Theses

The microbial communities that are present in and on vertebrates are collectively called the microbiome. The composition of a microbiome is dependent upon the host, the environment, and evolution. There has been extensive research on the bacterial composition of host-associated microbiomes, however, there has been much less work on the archaeal composition of host-associated microbiomes. Archaea have previously been assumed to primarily exist in extreme environments, but this may not be true and has been influenced by their generally low abundance and methodological difficulties in detection. It is possible they are consistent members of diverse host-associated microbiomes.

Archaea-specific PCR primers …

Advances In Methods For Trna Sequencing And Quantification, Nigam H. Padhiar, Upendra Katneni, Anton A. Komar, Yuri Motorin, Chava Kimchi-Sarfaty

Biological, Geological, and Environmental Faculty Publications

In the past decade tRNA sequencing (tRNA-seq) has attracted considerable attention as an important tool for the development of novel approaches to quantify highly modified tRNA species and to propel tRNA research aimed at understanding the cellular physiology and disease and development of tRNA-based therapeutics. Many methods are available to quantify tRNA abundance while accounting for modifications and tRNA charging/acylation. Advances in both library preparation methods and bioinformatic workflows have enabled developments in next-generation sequencing (NGS) workflows. Other approaches forgo NGS applications in favor of hybridization-based approaches. In this review we provide a brief comparative overview of various tRNA quantification …

Bioinformatics Characterization Of Variants Of Uncertain Significance In Pediatric Sensorineural Hearing Loss, Sloane Clay, Adele Evans, Regina Zambrano, David Otohinoyi, Chindo Hicks, Fern Tsien

School of Medicine Faculty Publications

Introduction: Rapid advancements in Next Generation Sequencing (NGS) and bioinformatics tools have allowed physicians to obtain genetic testing results in a more rapid, cost-effective, and comprehensive manner than ever before. Around 50% of pediatric sensorineural hearing loss (SNHL) cases are due to a genetic etiology, thus physicians regularly utilize targeted sequencing panels that identify variants in genes related to SNHL. These panels allow for early detection of pathogenic variants which allows physicians to provide anticipatory guidance to families. Molecular testing does not always reveal a clear etiology due to the presence of multigenic variants with varying classifications, including the presence …

Bnfo 135-002: Programming For Bioinformatics​​, Jun Wu

Computer Science Syllabi

No abstract provided.

Using Single Cell Genomics To Explore The Impact Of Marine Viruses On Microbial Respiration., Paxton Tomko

MCB Articles

Viral metabolic reprograming of marine prokaryotes, through the use of virally encoded auxiliary metabolic genes (AMGs), plays a critical role in marine ecosystem function by influencing biochemical cycles and genetic diversity in these environments. Despite the fundamental role viruses play in global environmental ecosystems, they remain an understudied aspect of microbial ecology and evolution, in part due to the methods available for studying virus host interactions in natural systems. Thus far, metagenomic analyses have been used to study the interactions of virus host pairs, but these types of analyses have their limitations in accurately linking viruses to hosts, or culture-based …

Developing Partnerships For Academic Data Science Consulting And Collaboration Units, Marianne Huebner, Laura Bond, Felesia Stukes, Joel Herndon, David J. Edwards, Gina-Maria Pomann

Biomolecular Research Institute Publications and Presentations

Data science consulting and collaboration units (DSUs) are core infrastructure for research at universities. Activities span data management, study design, data analysis, data visualization, predictive modelling, preparing reports, manuscript writing and advising on statistical methods and may include an experiential or teaching component. Partnerships are needed for a thriving DSU as an active part of the larger university network. Guidance for identifying, developing and managing successful partnerships for DSUs can be summarized in six rules: (1) align with institutional strategic plans, (2) cultivate partnerships that fit your mission, (3) ensure sustainability and prepare for growth, (4) define clear expectations in …

A Comprehensive Multi-Omics Analysis Reveals Unique Signatures To Predict Alzheimer’S Disease, Michael Vacher, Rodrigo Canovas, Simon M. Laws, James D. Doecke

Research outputs 2022 to 2026

Background: Complex disorders, such as Alzheimer’s disease (AD), result from the combined influence of multiple biological and environmental factors. The integration of high-throughput data from multiple omics platforms can provide system overviews, improving our understanding of complex biological processes underlying human disease. In this study, integrated data from four omics platforms were used to characterise biological signatures of AD. Method: The study cohort consists of 455 participants (Control:148, Cases:307) from the Religious Orders Study and Memory and Aging Project (ROSMAP). Genotype (SNP), methylation (CpG), RNA and proteomics data were collected, quality-controlled and pre-processed (SNP = 130; CpG = 83; RNA …

Engaging Students In A Genetics Course-Based Undergraduate Research Experience Utilizing Caenorhabditis Elegans In Hybrid Learning To Explore Human Disease Gene Variants, Natalie Forte, Virginia Veasey, Bethany Christie, Amira Carter, Marli Hanks, Alan Holderfield, Taylor Houston, Anil Challa, Ashley Turner

Research, Publications & Creative Work

Genetic analysis in model systems using bioinformatic approaches provides a rich context for a concrete and conceptual understanding of gene structure and function. With the intent to engage students in research and explore disease biology utilizing the nematode Caenorhabditis elegans model, we developed a semester-long course-based undergraduate research experience (CURE) in a hybrid (online/in-person) learning environment—the gene-editing and evolutionary nematode exploration CURE (GENE-CURE). Using a combination of bioinformatic and molecular genetic tools, students performed structure-function analysis of disease-associated variants of uncertain significance (VUS) in human orthologs. With the aid of a series of workshop-style research sessions, students worked in teams …

Convolutional Neural Network-Based Gene Prediction Using Buffalograss As A Model System, Michael Morikone

Complex Biosystems PhD Program: Dissertations

The task of gene prediction has been largely stagnant in algorithmic improvements compared to when algorithms were first developed for predicting genes thirty years ago. Rather than iteratively improving the underlying algorithms in gene prediction tools by utilizing better performing models, most current approaches update existing tools through incorporating increasing amounts of extrinsic data to improve gene prediction performance. The traditional method of predicting genes is done using Hidden Markov Models (HMMs). These HMMs are constrained by having strict assumptions made about the independence of genes that do not always hold true. To address this, a Convolutional Neural Network (CNN) …

Repurposing Normal Chromosomal Microarray Data To Harbor Genetic Insights Into Congenital Heart Disease, Nephi Walton, Hoang Nguyen, Sara Procknow, Darren Johnson, Alexander Anzelmi, Patrick Jay

Department of Medicine Faculty Papers

About 15% of congenital heart disease (CHD) patients have a known pathogenic copy number variant. The majority of their chromosomal microarray (CMA) tests are deemed normal. Diagnostic interpretation typically ignores microdeletions smaller than 100 kb. We hypothesized that unreported microdeletions are enriched for CHD genes. We analyzed "normal" CMAs of 1762 patients who were evaluated at a pediatric referral center, of which 319 (18%) had CHD. Using CMAs from monozygotic twins or replicates from the same individual, we established a size threshold based on probe count for the reproducible detection of small microdeletions. Genes in the microdeletions were sequentially filtered …

A Prospective Randomized Clinical Trial To Assess Antibiotic Pocket Irrigation On Tissue Expander Breast Reconstruction, Jennifer N Walker, Blake M Hanson, Tayler Hunter, Shelby R Simar, Jesus M Duran Ramirez, Chloe L P Obernuefemann, Rajiv P Parikh, Marissa M Tenenbaum, Julie A Margenthaler, Scott J Hultgren, Terence M Myckatyn

Student and Faculty Publications

Bacterial infection is the most common complication following staged post-mastectomy breast reconstruction initiated with a tissue expander (TE). to limit bacterial infection, antibiotic irrigation of the surgical site is commonly performed despite little high-quality data to support this practice. We performed a prospective randomized control trial to compare the impact of saline irrigation alone to a triple antibiotic irrigation regimen (1 g cefazolin, 80 mg gentamicin, and 50,000 units of bacitracin in 500 mL of saline) for breast implant surgery. The microbiome in breasts with cancer (

Bnfo 135: Programming For Bioinformatics​​, Jun Wu

Computer Science Syllabi

No abstract provided.

Generative Ai-Assisted Pathway Analysis And Interpretation Of Rna-Seq Experiment Data, Junguk Hur

AI Assignment Library

No abstract provided.

Establishment Of A Consensus Protocol To Explore The Brain Pathobiome In Patients With Mild Cognitive Impairment And Alzheimer's Disease: Research Outline And Call For Collaboration., Richard Lathe, Nikki M Schultek, Brian J. Balin, Garth D Ehrlich, Lavinia Alberi Auber, George Perry, Edward B Breitschwerdt, David B Corry, Richard L Doty, Robert A Rissman, Peter L Nara, Ruth Itzhaki, William A Eimer, Rudolph E Tanzi

PCOM Scholarly Works

Microbial infections of the brain can lead to dementia, and for many decades microbial infections have been implicated in Alzheimer's disease (AD) pathology. However, a causal role for infection in AD remains contentious, and the lack of standardized detection methodologies has led to inconsistent detection/identification of microbes in AD brains. There is a need for a consensus methodology; the Alzheimer's Pathobiome Initiative aims to perform comparative molecular analyses of microbes in post mortem brains versus cerebrospinal fluid, blood, olfactory neuroepithelium, oral/nasopharyngeal tissue, bronchoalveolar, urinary, and gut/stool samples. Diverse extraction methodologies, polymerase chain reaction and sequencing techniques, and bioinformatic tools will …

A Review Of How Bioinformatics And Genome Sequencing Are Affecting Precision Medicine, Taylor S. Hickey

Honors Theses

Advancement in genomic sequencing and bioinformatics methods have been affecting biomedical research through precision medicine, especially in the area of cancer. Vaccine therapies can be developed using neoantigens that target specific mutations in tumors. The goals of this research are to identify mutations that lead to cancer and then define subpopulations in which patients can easily be identified. The future goal is to have targeted vaccines that are specific to each subpopulation ready to be used in treatment of their cancer. Limitations to reaching these goals have been due to tumor heterogeneity, cancer location, and difficulty in creating neoantigens for …

High Expression Of Talin-1 Is Associated With Tumor Progression And Recurrence In Melanoma Skin Cancer Patients., Yasaman Rezaie, Fahimeh Fattahi, Baharnaz Mashinchi, Kambiz Kamyab Hesari, Sahar Montazeri, Elham Kalantari, Zahra Madjd, Leili Saeednejad Zanjani

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Talin-1 as a component of multi-protein adhesion complexes plays a role in tumor formation and migration in various malignancies. This study investigated Talin-1 in protein levels as a potential prognosis biomarker in skin tumors.

METHODS: Talin-1 was evaluated in 106 skin cancer (33 melanomas and 73 non-melanomas skin cancer (NMSC)) and 11 normal skin formalin-fixed paraffin-embedded (FFPE) tissue samples using immunohistochemical technique on tissue microarrays (TMAs). The association between the expression of Talin-1 and clinicopathological parameters, as well as survival outcomes, were assessed.

RESULTS: Our findings from data minings through bioinformatics tools indicated dysregulation of Talin-1 in mRNA levels …

Hr Gene Variants Identified In Mexican Patients With Alopecia Areata, Andrés Ortiz-Ramírez, María Cristina Hernández-Jiménez, Iliana Berenice Guardiola-Avila, Erick De Jesús De Luna-Santillana, Amanda Alejandra Oliva-Hernández, María Lourdes Altamirano-García, Karina Janett Juárez-Rendón

School of Medicine Publications and Presentations

Alopecia Areata (AA) is a multifactorial, dermatological disease characterized by non-scarring hair loss. Alterations in candidate genes, such as HR (Hairless), could represent a risk factor for its development. The aim of this study was to search for and analyze variants in exons 3, 15 and 17 of the HR gene in Mexican patients with AA. A total of 30 samples from both AA patients and healthy donors were analyzed in this study. Exons were amplified and sequenced using the Sanger method. Descriptive statistics and χ2 tests were used in the analysis of clinical–demographic characteristics and the comparison of allelic/genotypical …

Comprehensive Smn1 And Smn2 Profiling For Spinal Muscular Atrophy Analysis Using Long-Read Pacbio Hifi Sequencing., Xiao Chen, John Harting, Emily G. Farrow, Isabelle Thiffault, Dalia Kasperaviciute, Genomics England Research Consortium, Alexander Hoischen, Christian Gilissen, T Pastinen, Michael A. Eberle

Manuscripts, Articles, Book Chapters and Other Papers

Spinal muscular atrophy, a leading cause of early infant death, is caused by bi-allelic mutations of SMN1. Sequence analysis of SMN1 is challenging due to high sequence similarity with its paralog SMN2. Both genes have variable copy numbers across populations. Furthermore, without pedigree information, it is currently not possible to identify silent carriers (2+0) with two copies of SMN1 on one chromosome and zero copies on the other. We developed Paraphase, an informatics method that identifies full-length SMN1 and SMN2 haplotypes, determines the gene copy numbers, and calls phased variants using long-read PacBio HiFi data. The SMN1 and SMN2 copy-number …

Plasma Protein Profiling Analysis In Patients With Atrial Fibrillation Before And After Three Different Ablation Techniques, Menglu Lin, Yangyang Bao, Zunhui Du, Yanting Zhou, Ning Zhang, Changjian Lin, Yinyin Xie, Ruihong Zhang, Qiheng Li, Jinwei Quan, Tingfang Zhu, Yuan Xie, Cathy Xu, Yun Xie, Yue Wei, Qingzhi Luo, Wenqi Pan, Lingjie Wang, Tianyou Ling, Qi Jin, Liqun Wu, Tong Yin, Yucai Xie

Student Publications

Background: There are controversies on the pathophysiological alteration in patients with atrial fibrillation (AF) undergoing pulmonary vein isolation using different energy sources.

Objectives: We evaluated the changes in plasma proteins in acute phase post-ablation in patients receiving cryoballoon ablation, radiofrequency balloon ablation, or radiofrequency ablation.

Methods: Blood samples from eight healthy controls and 24 patients with AF were taken on the day of admission, day 1, and day 2 post-ablation and analyzed by the Olink proximity extension assay. Proteins were identified and performed with enrichment analysis. Protein-protein interaction network and module analysis were conducted using Cytoscape software.

Results: Of 181 …

Approaches To Avoid Proteolysis During Protein Expression And Purification, Gary T. Henehan, Barry J. Ryan, Gemma K. Kinsella

Books/Book Chapters/ Proceedings

All cells contain proteases, which hydrolyze the peptide bonds between amino acids of a protein backbone. Typically, proteases are prevented from nonspecific proteolysis by regulation and by their physical separation into different subcellular compartments; however, this segregation is not retained during cell lysis, which is the initial step in any protein isolation procedure. Prevention of proteolysis during protein purification often takes the form of a two-pronged approach: first, inhibition of proteolysis in situ, followed by the early separation of the protease from the protein of interest via chromatographic purification. Protease inhibitors are routinely used to limit the effect of the …

Protein Extraction And Purification By Differential Solubilization, Barry J. Ryan, Gemma K. Kinsella, Gary T. Henehan

Books/Book Chapters/ Proceedings

The preparation of purified soluble proteins for biochemical studies is essential and the solubility of a protein of interest in various media is central to this process. Selectively altering the solubility of a protein is a rapid and economical step in protein purification and is based on exploiting the inherent physicochemical properties of a polypeptide. Precipitation of proteins, released from cells upon lysis, is often used to concentrate a protein of interest before further purification steps (e.g., ion exchange chromatography, size exclusion chromatography etc).

Recombinant proteins may be expressed in host cells as insoluble inclusion bodies due to various influences …

Acafinder: Genome Mining For Anti-Crispr-Associated Genes, Bowen Yang, Jinfang Zheng, Yanbin Yin

Food for Health: Publications

Anti-CRISPR (Acr) proteins are encoded by (pro)viruses to inhibit their host’s CRISPR-Cas systems. Genes encoding Acr and Aca (Acr associated) proteins often colocalize to form acr-aca operons. Here, we present AcaFinder as the first Aca genome mining tool. AcaFinder can (i) predict Acas and their associated acr-aca operons using guilt-by-association (GBA); (ii) identify homologs of known Acas using an HMM (Hidden Markov model) database; (iii) take input genomes for potential prophages, CRISPR-Cas systems, and self-targeting spacers (STSs); and (iv) provide a standalone program (https://github.com/boweny920/AcaFinder) and a web server (http://aca .unl.edu/Aca). AcaFinder was applied to mining over …

Safety Assessment Of Novel Foods And Food Proteins, Niloofar Moghadam Maragheh

Department of Food Science and Technology: Dissertations, Theses, and Student Research

The global food market needs to grow and supply food demand to feed the growing world population. Alternative food proteins, including novel sources of safe foods and ingredients, are the candidates that could provide more environmentally sustainable choices, animal welfare, and consumers health. Novel foods and food proteins must undergo premarket safety evaluations including allergenicity assessment to reduce the risk of cross-reactivity with known allergens and uncharacterized risk to food allergic individuals. This research addressed the safety assessment of some novel foods and food ingredients using the study of stability of proteins in pepsin and sequence identity analysis in the …