Genomics Commons^™

Investigating The Taxonomic Uncertainties Of Potentilla Rupincola, Natalie Elizabeth Hieber

Master's Theses

Landscape stewardship is an integral role for land managers that becomes more important when rare or endangered species occur within managed areas. Conservation across the landscape is a primary concern for land managers, but resources allocated for conservation can be limited due to many competing goals. Taxonomic uncertainty surrounding rare and endangered taxa, particularly plant taxa, that have historically been classified solely using morphological features further complicates conservation planning. One such taxon is Potentilla rupincola, a rare plant endemic to the eastern Rocky Mountains in Colorado. For over a century, botanists have debated whether P. rupincola is a distinct species …

The Hitchhiker's Guide To The Host: Fleas And The History Of Pikas In North America, Josh Pletcher

All NMU Master's Theses

Parasite phylogenetics can offer windows into the cryptic evolutionary history of hosts, often highlighting events that are not recorded by the phylogenetics of the host. Pikas (small lagomorphs) host a diverse parasite community comprising endoparasites (e.g., coccidians, nematodes, and cestodes) and ectoparasites (e.g., fleas and mites). Phylogenetic analysis of pika endoparasites has revealed pikas evolved in Asia and colonized North America in two waves, and that contact between these two pika lineages allowed parasites to be transferred from one lineage to another and to survive the extinction of their original host. To uncover these cryptic histories, understanding the biogeography of …

Population Structure And Connectivity Of Atlantic Nurse Sharks (Ginglymostoma Cirratum) In The Bahamas And Outlying Areas, Baylie A. Fadool

School of Natural Resources: Dissertations, Theses, and Student Research

Understanding animal ecosystem dynamics and behavior at the individual and population levels is essential for identifying life-history patterns and important areas for management and conservation. Marine fish species often face minimal geographic barriers to movement, but environmental (temperature, salinity, current) or intrinsic barriers (philopatry, site fidelity) can dictate gene flow. Atlantic nurse sharks (Ginglymostoma cirratum) are an International Union for Conservation of Nature (IUCN) listed ‘vulnerable’ species and present a unique opportunity to investigate patterns of population structure and connectivity in large-bodied sharks. They are benthic and display reproductive philopatry, with recent work suggesting they have the capacity …

Toward Interpretable Multi-Omics Multimodal Biomedical Artificial Intelligence, Yanjun Lyu

Computer Science and Engineering Dissertations

The complexity of human disease arises from biological processes that unfold across multiple scales, from molecular variation through cellular function, tissue organisation, brain phenotypes, each of which is associated with distinct measurement modalities, regularities, and characteristic. Contemporary biomedical artificial intelligence has brought the opportunity to reveal the complexity with in; however, its methodological default, in which models are trained on most readily available modality, does not adequately engage with the multi-scale connected structure by which biological meaning is constituted. The research area of multi-omics and multi-modal AI for biomedicine remains at an early exploratory stage, and the work presented in …

Microbial Community Structure In Global Soils, Matthew Jabro

CMC Senior Theses

Soil harbors the most diverse microbial communities on Earth, yet whether predictable community types exist across biomes and whether taxonomic composition encodes habitat of origin remain open questions at global scale. This thesis addresses both questions by applying unsupervised clustering and supervised classification to transformed 16S ribosomal RNA (rRNA) amplicon profiles from two independent datasets: the global topsoil survey of Bahram et al. (193 samples) and the Earth Microbiome Project (EMP) soil subset of Thompson et al. (2,209 samples). Application of a sample clustering method based on a mixture of Gaussian Graphical Models (MixGGM) identified 19 clusters in the topsoil …

An Ensemble Classifier For Ordinal Outcomes In High-Dimensional Genomics Data, Heranga K. Rathnasekara, Sinjini Sikdar

Mathematics & Statistics Faculty Publications

Analysis of genomics data for predicting disease outcomes is a fast-growing field in medical research. There often exist categorical, specifically, ordinal outcomes that need to be predicted based on genomic profiles. This has led to recent development of some high-dimensional ordinal classification methods that can address the large dimensionality of the genomic covariate set. These high-dimensional ordinal models tend to vary widely in their performance depending on the data they are applied to and the evaluation criteria used. In this article, we outline an ensemble ordinal classifier that integrates different ordinal modeling approaches through bootstrap-based model evaluation, multi-metric performance assessment, …

Benchmarking Dna Foundation Models For Genomic And Genetic Tasks, Haonan Feng, Lang Wu, Bingxin Zhao, Chad Huff, Jianjun Zhang, Jia Wu, Lifeng Lin, Peng Wei, Chong Wu

School of Medicine Faculty Publications

The rapid evolution of DNA foundation models promises to revolutionize genomics, yet comprehensive evaluations are lacking. Here, we present a comprehensive, unbiased benchmark of five models (DNABERT-2, Nucleotide Transformer V2, HyenaDNA, Caduceus-Ph, and GROVER) across diverse genomic and genetic tasks including sequence classification, gene expression prediction, variant effect quantification, and topologically associating domain (TAD) region recognition, using zero-shot embeddings. Our analysis reveals that mean token embedding consistently and significantly improves sequence classification performance, outperforming other pooling strategies. Model performance varies among tasks and datasets; while general purpose DNA foundation models showed competitive performance in pathogenic variant identification, they were less …

Performance Analysis Of Computational Methods For Predicting Protein Function In Rare Diseases, Aichetou Mohamed Sidiya, Hanin Alzaher, Razan Almahdi, Tayeb Brahimi

Effat Undergraduate Research Journal

Protein function prediction is crucial for understanding the underlying mechanisms of rare diseases. With the increasing availability of computational methods including machine learning-based approaches, network-based methods, and sequence-based methods, predicting protein functions has become more accessible. However, it is not clear which of these methods performs better or how they compare to each other in terms of accuracy, efficiency, and scalability. In this study, we evaluate several computational methods for predicting protein functions in rare diseases using key performance indicators (KPIs). We analyze the strengths and weaknesses of each method and provide recommendations for researchers and clinicians interested in using …

Emerging Technologies For Forensic Genetic Identification, Lilly Llanos

Senior Honors Theses

There are many new innovations in forensic science that are being developed for the identification of biological evidence. These techniques include next-generation DNA sequencing, DNA phenotyping, and forensic genetic genealogy. This thesis will explore each, as well as newer applications of proteomics. The methodologies, reliability, practicality of cost and training, moral implications, and past research of each will be discussed. Finally, some ideas for future research and steps to drive growth and greater understanding will be suggested. This will encourage further innovations and the increased acceptance of forensic evidence in court. Each method was found to have both advantages and …

The Role Of Secondary And Tertiary Structure In The Cap-Independent Translation Of Fgf-9 And Hif-1-Alpha, Amanda Michelle Whittaker

Dissertations, Theses, and Capstone Projects

Under normoxic conditions, eukaryotes initiate translation of RNA through eIF4E recognition of the 5’ cap. However, under cellular stress, eukaryotic translation must be initiated through a 4E-independent, or “cap-independent” mechanism, involving eukaryotic initiation factor 4G (eIF4G) binding directly to the 5’ untranslated regions (5’ UTR) of the RNA. eIF4G binding then recruits the ribosome to the transcript. While this mechanism is useful for translation of apoptotic transcripts and transcripts involved in cell survival, cap-independent translation is also utilized by oncogenic RNA for tumorigenesis. Previous work by our lab and others has categorized this recruitment and initiation mechanism as either internal-ribosome-entry-site …

Assessment Of The Genetic Population Structure And Extent Of Clonality In A Rare Serpentine Endemic, Lathyrus Biflorus T.W. Nelson & J.P. Nelson (Fabaceae), Using Ddrad Sequencing, Ashley Dickinson

Cal Poly Humboldt theses and projects

Lathyrus biflorus, or the two-flowered pea, is a rare herbaceous perennial restricted to a single population in Northern California. The species is considered critically imperiled but remains unprotected under state or federal endangered species acts. Despite its rarity, little is known about its life history, reproductive biology, or genetic diversity. Using genome-wide reduced representation sequencing, this study aimed to address these gaps by investigating the molecular evidence of clonality, the number and diversity of genets (unique genetic individuals which can be made up of one or many clonal units or ramets), and overall genetic health of the population. My …

A Bayesian Deep Segmentation Framework For Glioblastoma Tumor Segmentation Using Follow-Up Mris, Tanjida Kabir, Kang-Lin Hsieh, Luis Nunez, Yu-Chun Hsu, Juan C Rodriguez Quintero, Octavio Arevalo, Kangyi Zhao, Jay-Jiguang Zhu, Roy F Riascos, Mahboubeh Madadi, Xiaoqian Jiang, Shayan Shams

Faculty, Staff and Student Publications

Background: Glioblastoma (GBM) is the most common malignant brain tumor with an abysmal prognosis. Since complete tumor cell removal is impossible due to the infiltrative nature of GBM, accurate measurement is paramount for GBM assessment. Preoperative magnetic resonance images (MRIs) are crucial for initial diagnosis and surgical planning, while follow-up MRIs are vital for evaluating treatment response. The structural changes in the brain caused by surgical and therapeutic measures create significant differences between preoperative and follow-up MRIs. In clinical research, advanced deep learning models trained on preoperative MRIs are often applied to assess follow-up scans, but their effectiveness in this …

Methods In Statistics, Machine Learning, And Deep Learning For Combining Multi-Omics Dataset, Md Mutasim Billah

Dissertations, Master's Theses and Master's Reports

Transcriptome-wide association studies (TWAS) have emerged as a powerful strategy to bridge genome-wide association studies (GWAS) with gene regulatory mechanisms by integrating genotypic data with gene expression data. While early TWAS methods typically rely on linear models and single-tissue expression references, recent advances underscore the need for flexible, multi-tissue approaches that can capture heterogeneous regulatory architectures and tissue-specific expression patterns. This dissertation introduces a three‑part research project that advances multi‑tissue transcriptome‑wide association studies (TWAS) along complementary axes of methodology, statistical power, and modelling flexibility.

In chapter One, TWAS‑CTL introduces a two‑stage cross‑tissue learner that trains any user‑chosen single‑tissue imputers (STLs) …

Genomic Data Science Approaches For Understanding Human Diseases, Snehal Shah

All Dissertations

The intricate interplay of genetic predisposition, environmental influences, and lifestyle acts as the multifactorial landscape of diseases. Understanding this complexity presents a significant challenge. Molecular insights into disease mechanisms, particularly the interactions of DNA, RNA, and proteins with environmental and lifestyle factors, have revolutionized disease diagnosis, prognosis, and treatment. High-throughput technologies, such as next-generation sequencing, generate large amounts of molecular data, holding a wealth of knowledge. These datasets unveil the roles of genes and their interactions with various factors through analysis, shedding light on previously unknown molecular mechanisms underlying disease pathogenesis. Furthermore, they facilitate the discovery of biomarkers crucial for …

Ocular Gene Transfer In The Spotlight: Implications Of Newspaper Content For Clinical Communications, Shelly Benjaminy, Tania M. Bubela

Office of the Provost

Background: Ocular gene transfer clinical trials are raising hopes for blindness treatments and attracting media attention. News media provide an accessible health information source for patients and the public, but are often criticized for overemphasizing benefits and underplaying risks of novel biomedical interventions. Overly optimistic portrayals of unproven interventions may influence public and patient expectations; the latter may cause patients to downplay risks and over-emphasize benefits, with implications for informed consent for clinical trials. We analyze the news media communications landscape about ocular gene transfer and make recommendations for improving communications between clinicians and potential trial participants in light of …

Evaluating Past Progress And Assessing Prediction Breeding Strategies For Sustained Genetic Gains In The Louisiana Sugarcane Variety Development Program, Brayden A. Blanchard

LSU Doctoral Dissertations

The aim of this dissertation is to outline important considerations for the Louisiana Sugarcane Variety Development Program (LSVDP) as it pertains to historical progress, impact, goal setting, and new strategies for continued genetic gains. Industry progress was evaluated with robust regression models to quantify rates of productivity gains. Over the last 50 years, statistically significant productivity gains were identified in sucrose content (45%), cane yield (32.2%), and sugar yield (93%) while pairwise comparisons of decades showed that progress was incremental rather than rapid and sustained once achieved. The decade from 1990-1999 was identified as the only decade with a significant …

Discovery Of Runs-Of-Homozygosity Diplotype Clusters And Their Associations With Diseases In Uk Biobank, Ardalan Naseri, Degui Zhi, Shaojie Zhang

Faculty, Staff and Student Publications

Runs-of-homozygosity (ROH) segments, contiguous homozygous regions in a genome were traditionally linked to families and inbred populations. However, a growing literature suggests that ROHs are ubiquitous in outbred populations. Still, most existing genetic studies of ROH in populations are limited to aggregated ROH content across the genome, which does not offer the resolution for mapping causal loci. This limitation is mainly due to a lack of methods for the efficient identification of shared ROH diplotypes. Here, we present a new method, ROH-DICE (runs-of-homozygous diplotype cluster enumerator), to find large ROH diplotype clusters, sufficiently long ROHs shared by a sufficient number …

Big Life-Science: Study Of Omics From Microscopic To Mesoscopic Scales, Jiarui Wu

Bulletin of Chinese Academy of Sciences (Chinese Version)

The human genome project at the turn of the century opened a new era of life science research and formed various omics characterized by holistic high-throughput research. The initial omics research was mainly carried out at the molecular level, such as genomics, transcriptomics, proteomics, etc., showing a new paradigm of data-driven research. With the development of research technologies, the omics research has risen to the mesoscopic level, the representative is the “Human Cell Atlas” project launched in 2017. At present, researchers have been able to carry out omics research at the level of tissues, organs, and even individuals, and resulted …

Promoting Ecosystem Based Marine Management Through A Marine Ecological Classification And Zoning System, Wenhai Lu, Xiao Li, Meng Cui

Bulletin of Chinese Academy of Sciences (Chinese Version)

Ecosystem based ocean management is an important means of building marine ecological civilization. The current marine ecological classification and zoning in China comprehensively sorts out the types and natural geographical characteristics of marine ecosystems, divided the Chinese seas and adjacent waters into several levels of ecological spatial units according to different scales, effectively characterizes the geographical distribution features of marine biological communities and their habitats, and provides effective support for ecosystem based marine management. This study analyzed the practical significance of marine ecological classification and zoning. Based on a review of the development of marine ecological classification and zoning, this …

Tissue-Specific Atlas Of Trans-Models For Gene Regulation Elucidates Complex Regulation Patterns, Robert Dagostino, Assaf Gottlieb

Faculty, Staff and Student Publications

BACKGROUND: Deciphering gene regulation is essential for understanding the underlying mechanisms of healthy and disease states. While the regulatory networks formed by transcription factors (TFs) and their target genes has been mostly studied with relation to cis effects such as in TF binding sites, we focused on trans effects of TFs on the expression of their transcribed genes and their potential mechanisms.

RESULTS: We provide a comprehensive tissue-specific atlas, spanning 49 tissues of TF variations affecting gene expression through computational models considering two potential mechanisms, including combinatorial regulation by the expression of the TFs, and by genetic variants within the …

Identifying Environmental And Genetic Risk Factors Of Diseases In Case-Control Studies, Siting Li

Dartmouth College Ph.D Dissertations

In response to the increasing efforts in disease prevention and treatment, this thesis applies statistical methods to investigate environmental and genetic risk factors associated with two diseases: bladder cancer and amyotrophic lateral sclerosis (ALS). For bladder cancer, we investigated the association between toenail metal mixture and bladder cancer risk, along with gene expression levels associated with bladder cancer risk. For ALS, our investigation involves identifying genetic variants and gene expression levels associated with ALS risk and exploring gene-smoking interactions linked to ALS risk.

In chapter two, we developed an adaptive-mixture-categorization (AMC)-based g-computation method combining g-computation with optimized exposure categorization. We …

Sox On Tumors, A Comfort Or A Constraint?, Junqing Jiang, Yufei Wang, Mengyu Sun, Xiangyuan Luo, Zerui Zhang, Yijun Wang, Siwen Li, Dian Hu, Jiaqian Zhang, Zhangfan Wu, Xiaoping Chen, Bixiang Zhang, Xiao Xu, Shuai Wang, Shengjun Xu, Wenjie Huang, Limin Xia

Faculty, Staff and Student Publications

The sex-determining region Y (SRY)-related high-mobility group (HMG) box (SOX) family, composed of 20 transcription factors, is a conserved family with a highly homologous HMG domain. Due to their crucial role in determining cell fate, the dysregulation of SOX family members is closely associated with tumorigenesis, including tumor invasion, metastasis, proliferation, apoptosis, epithelial-mesenchymal transition, stemness and drug resistance. Despite considerable research to investigate the mechanisms and functions of the SOX family, confusion remains regarding aspects such as the role of the SOX family in tumor immune microenvironment (TIME) and contradictory impacts the SOX family exerts on tumors. This review summarizes …

The Hsp90-Myc-Cdk9 Network Drives Therapeutic Resistance In Mantle Cell Lymphoma, Fangfang Yan, Vivian Jiang, Alexa Jordan, Yuxuan Che, Yang Liu, Qingsong Cai, Yu Xue, Yijing Li, Joseph Mcintosh, Zhihong Chen, Jovanny Vargas, Lei Nie, Yixin Yao, Heng-Huan Lee, Wei Wang, Johnnelson R Bigcal, Maria Badillo, Jitendra Meena, Christopher Flowers, Jia Zhou, Zhongming Zhao, Lukas M Simon, Michael Wang

Faculty, Staff and Student Publications

Brexucabtagene autoleucel CAR-T therapy is highly efficacious in overcoming resistance to Bruton's tyrosine kinase inhibitors (BTKi) in mantle cell lymphoma. However, many patients relapse post CAR-T therapy with dismal outcomes. To dissect the underlying mechanisms of sequential resistance to BTKi and CAR-T therapy, we performed single-cell RNA sequencing analysis for 66 samples from 25 patients treated with BTKi and/or CAR-T therapy and conducted in-depth bioinformatics™ analysis. Our analysis revealed that MYC activity progressively increased with sequential resistance. HSP90AB1 (Heat shock protein 90 alpha family class B member 1), a MYC target, was identified as early driver of CAR-T resistance. CDK9 …

Research On Innovative Development Path And Policy Guarantee Of China’S Synthetic Biology Industry, Hongjun Geng, Chang Wang

Bulletin of Chinese Academy of Sciences (Chinese Version)

Synthetic biology is hailed as the third revolution in life sciences after the discovery of the DNA double helix structure and genomic technology, and is the core driving force for the leapfrog development of next-generation biomanufacturing and the future bioeconomy, opening up an opportunity window for the reshaping of the global manufacturing map. How to strategically position the synthesis biology industry and seize the strategic high ground in the industry is a core topic of interest for global science and technology powers and manufacturing powers. Based on the identification of problems in the development of China’s synthesis biology industry, this …

Recent Progress And Perspectives On Development Of Gene Editing Tools, Zixian Liu, Chengping Li, Gogo Jun-Jie Liu

Bulletin of Chinese Academy of Sciences (Chinese Version)

The gene editing field has witnessed remarkable advancements in recent years, leading to the establishment and refinement of multidimensional gene editing platforms. These innovations have enabled precise targeted gene knockout, repair, and insertion. These tools have stimulated significant progress in fundamental research, therapeutics, agriculture, environment protection, and industrial applications. In this review, we provide a comprehensive overview of the milestones in gene editing tool development and offer perspectives on potential future directions for this rapidly evolving field.

Creation Of A Digital Storage System For Genome Sequencing Metadata, Jacquelin W. Olexa

Undergraduate Theses, Professional Papers, and Capstone Artifacts

As the field of computational genomics continues to expand in both potential and application, it is now more imperative than ever to ensure that massive genetic sequencing datasets are properly stored in an accessible manner. This project sought to establish a practical, user-friendly, secure system for a genomics research lab (the Good Lab; thegoodlab.org) at the University of Montana. A MySQL database and connected web application was ruled the best configuration to maximize utility and accessibility for the lab’s researchers. Building the logical framework for the database, creating the server, and sourcing data occurred over several months. The dataset ranged …

Chemical Synthesis Of Sensitive Dna, Komal Chillar

Dissertations, Master's Theses and Master's Reports

Over the past decades, researchers have tried various chemical methods to synthesize modified oligodeoxynucleotides (ODNs, i.e. short segments of DNAs). Traditional ODN synthesis methods require strong basic, and nucleophilic conditions for the deprotection and cleavage of the ODN from the solid support. However, the sensitive ODNs containing labile functionalities are vulnerable to such harsh conditions. Sensitive ODNs have a wide range of applications in research and pharmaceuticals. To synthesize sensitive ODNs, researchers devised different strategies but no practical methods have been developed. To overcome these challenges, we developed alkyl Dim alkyl Dmoc technology. This innovative technology uses weakly basic and …

Model-Based Deep Autoencoders For Clustering Single-Cell Rna Sequencing Data With Side Information, Xiang Lin

Dissertations

Clustering analysis has been conducted extensively in single-cell RNA sequencing (scRNA-seq) studies. scRNA-seq can profile tens of thousands of genes' activities within a single cell. Thousands or tens of thousands of cells can be captured simultaneously in a typical scRNA-seq experiment. Biologists would like to cluster these cells for exploring and elucidating cell types or subtypes. Numerous methods have been designed for clustering scRNA-seq data. Yet, single-cell technologies develop so fast in the past few years that those existing methods do not catch up with these rapid changes and fail to fully fulfil their potential. For instance, besides profiling transcription …

Identification Of Significant Gene Expression Changes Incorporating Heterogeneity In Perturbation Experiments, Katharine Cross

Honors Projects in Biological and Biomedical Sciences

Machine learning methods have been widely applied to the field of genomics and bioinformatics. Specifically utilizing novel machine learning algorithms to study gene-drug interactions has the potential to make a major positive impact on new drug discovery. It is possible that heterogeneity may exist within Vorinostat drug perturbation experiments due to the effects of the perturbations on the gene expressions. Thus, the challenge is to identify the most important genes in a high-dimensional setting while first identifying subpopulations to address population heterogeneity. In this work, clustering techniques are applied to first identify group sub-population structures in the gene expression changes …

Motif-Cluster: A Spatial Clustering Package For Repetitive Motif Binding Patterns, Mengyuan Zhou

School of Computing: Dissertations, Theses, and Student Research

Previous efforts in using genome-wide analysis of transcription factor binding sites (TFBSs) have overlooked the importance of ranking potential significant regulatory regions, especially those with repetitive binding within a local region. Identifying these homogenous binding sites is critical because they have the potential to amplify the binding affinity and regulation activity of transcription factors, impacting gene expression and cellular functions. To address this issue, we developed an open-source tool Motif-Cluster that prioritizes and visualizes transcription factor regulatory regions by incorporating the idea of local motif clusters. Motif-Cluster can rank the significant transcription factor regulatory regions without the need for experimental …