Computational Biology Commons^™

Data Curation And Integration For Cancer Cell Line Pharmacogenomics Analysis, Meric Kinali

Graduate Masters Theses

Cancer cell lines are essential resources for connecting genomic and molecular features with drug response and identifying biomarkers. Therefore, large-scale cancer cell line resources have been growing, but this introduces challenges such as data standardization, consistent annotation, matching identifiers, cross-database integration, and a reproducible computational framework. CellMiner Cross Database (CellMinerCDB) integrates pharmacogenomic datasets from multiple resources and provides a standardized analysis of cell lines across datasets. This thesis examines cancer cell line cross-databases and their importance in pharmacogenomics, with a particular focus on CellMinerCDB. As part of this work, I developed an R package for the gCSI (Genentech Cell Line …

Regulation Of Müllerian Duct Mesenchyme Transcription During Mammalian Sex Differentiation, Haowen Li, Richard R Behringer, Rachel D Mullen

Dissertations and Theses (Open Access)

Sp7/Osterix (Osx) encodes a zinc-finger transcription factor of the Specificity-protein family discovered by Nakashima et al. at the MD Anderson Cancer Center. While primarily recognized for its role in osteogenesis, Osx has also been implicated in mammalian reproductive development, particularly in male sex differentiation, where Müllerian Duct (MD) regression occurs, mediated by anti-Müllerian hormone (AMH) signaling. AMH-induced regression signals are transduced by the mesenchymal tissue surrounding the ductal structure, known as the Müllerian Duct mesenchyme (MDM). It was discovered that AMH signaling is necessary and sufficient for driving Osx expression in MDM. A previous transgenic mouse reporter …

Understanding Epigenomic Landscapes In Cancer Progression And Immunotherapy Response, Jonathan Schulz

Dissertations and Theses (Open Access)

Nonmutational epigenomic reprogramming has emerged as a key hallmark of cancer that plays crucial roles in tumor evolution during its progression and response to therapy. However, the extent and nature of epigenomic reprogramming remains poorly understood. This dissertation examines how epigenetic regulation shapes cancer progression and response to immunotherapy. Working at the intersection of cancer biology and computational genomics, it develops analytical frameworks for characterizing chromatin structure and DNA methylation across diverse tumor contexts and uses these frameworks to address two complementary biological questions: how promoter-associated chromatin organization varies across cancer types, and how epigenetic perturbation modulates tumor immunogenicity in …

Discovering The Genetics Underlying Speciation Traits In Heuchera (Coral Bells), Tajinder Singh

Honors Theses

Hybridization is a key evolutionary mechanism for generating biological diversity, ultimately shaping diversification and adaptation of plant lineages in natural and agroecosystems.  Our understanding of the frequency, distribution, and significance of hybridization is rapidly increasing, but the external driving forces that dictate why certain species hybridize, and others do not remain obscure. The physical traits that shape gene flow and trait sharing among species are likely to be among the key factors that directly control hybridization. Gene flow in most plants is mediated by pollinating insects and thus by pollination syndromes, which are suites of floral traits that have evolved …

Characterization And Advancement Of Molluscan Venom Gland Cell Model Systems, James V. Parziale

Dissertations, Theses, and Capstone Projects

Venomous mollusks, including cone snails and coleoid cephalopods, produce rich repertoires of bioactive peptides with profound effects on cellular physiology, yet there are few tractable experimental systems that exist to study their development, maintenance, and venom secretion. Although therapeutics such as the cone snail peptide Ziconotide demonstrate the biomedical potential of molluscan venoms, progress in understanding how venom glands form, function, and evolve has been hindered by the lack of reliable husbandry and the complete absence of in vitro cell models. Modern comparative genomics has revealed widespread convergent evolution across venomous lineages, but molluscan datasets remain underrepresented, limiting insights into …

Computational Comparative Genome Analysis Reveals The Characteristics Of Acinetobacter Baumannii C123 Strains, Jennilyn Nicole G. Mendoza

The Lasallian Journal of Health

Acinetobacter baumannii is a Gram-negative, aerobic and multi-drug resistant bacterial pathogen commonly associated with nosocomial infections. This species has several strains and is known to cause pneumonia, septi cemia, meningitis, urinary tract infection and wound infection which are associated with high mortality rates. This study focused on a genome-wide compari son among target C123 strain and 15 other reference strains to predict the overall properties, and resistance mechanisms of the C123 strain. A total of 16 whole genome sequence strains were retrieved from NCBI database for analysis. The selected strains were assem bled and annotated using computational tools. Further more, …

A Framework For Characterizing The Peripheral Immune Isonome Using Long-Read Single-Cell Rna Sequencing And Its Relevance To Neurological Disease, Patricia Hayes Doyle

Theses and Dissertations--Neuroscience

Long-read single-cell RNA sequencing provides an opportunity to understand human health and disease at isoform resolution, revealing cellular diversity and disease mechanisms difficult to resolve with bulk or short-read methodologies.

Using a modified PIPseq workflow and computational pipeline adapted for Oxford Nanopore (ONT) sequencing, we profiled isoform usage across immune cells, integrating marker expression and isoform discovery, generating the largest long-read single-cell dataset of human immune cells from a single individual to date. We identified non-canonical protein-coding variants of GZMB and CD3G enriched in unexpected cell types. We also discovered novel transcripts from CMC1 and LYAR with cell-type-specific signatures that …

A Persistent Homology Framework For Scrna-Seq: Assessing Clustering Robustness And Quantifying Preprocessing And Integration Effects On Topological Features., Jonah Daneshmand

Electronic Theses and Dissertations

As single-cell RNA sequencing (scRNA-seq) data expands, robust methods for integrating diverse datasets are critical. This dissertation applies Persistent Homology (PH), a technique from Topological Data Analysis (TDA), to a collection of scRNA-seq datasets spanning eight tissue types to quantify how data integration affects topological features and biological interpretability. We assessed global topological structure using Betti curves, Euler characteristics, and persistence landscapes across raw, normalized, and integrated data representations. Our analysis revealed a performance inversion: while conventional methods excelled on unintegrated data, high-granularity topological methods, particularly those sensitive to global data structure, became superior after integration. This suggests a synergy …

Topodino: Self-Supervised Topological Representation Learning For Neuronal Morphologies, Yasser Binbisher

Master's Theses

Neuronal cell types are categorized by transcriptomic identity, yet their morphological heterogeneity defies this classification. In response, researchers have adopted unsupervised graph representation learning as a tool to reveal morphological variation within single-class transcriptomic types. However, the complex geometry of neuronal morphology—especially long axons and dense dendrites—challenges graph neural networks, which struggle with message propagation across extended structures. To mitigate this, current approaches enforce sub-sampling on neuronal graphs and omit axons entirely, sacrificing critical biological features for computational efficiency. To overcome this trade-off, this thesis introduces TopoDINO, a self-supervised, topology-aware representation learning model designed to preserve the full hierarchical organization …

Understanding How Genetic Mutations Induce Oligodendrocyte Progenitors To Become Cancer Cells, Dennis Huang

Dissertations, Theses, and Capstone Projects

Gliomas are the most devastating adult brain tumors characterized by poor survival rate and limited options for treatment. Previous studies have shown that they are very heterogeneous and can be further sub-classified based on their transcriptional signature and the presence of specific mutations. One such subtype, is the “proneural glioma”, which is characterized by the enrichment in oligodendrocyte progenitor cell (OPC) transcripts and mutations in genes encoding for the tumor suppressor P53 (Trp53) and for Platelet Derived Grow Factor (PDGF) signaling. Since OPCs are the most abundant proliferative population in the adult brain, in this …

Network Analysis Of Antimicrobial Resistance In Staphylococcus Aureus: Characterization Of Hub Genes And Their Functional Implications, Md Imran Hasan, Davida Smyth, Jeong Yang, Ashley Teufel

Masters Theses (Archived)

Antimicrobial resistance is a major cause of morbidity and mortality in patients with S. aureus infections. In this study, we analyzed genes, molecular mechanisms, and pathways driving drug resistance in S. aureus using network analysis. Using whole-genome sequencing (WGS) data and systems biology approaches, we identified 229 AMR-associated genes and constructed a protein-protein interaction network among these genes. Through network topology and functional enrichment analyses, we not only confirmed their association with resistance, but also highlighted the central roles of these genes in resistance pathways, such as efflux, target replacement, and target protection, which are directly linked to multiple drug …

Developing A Small Molecule To Inhibit Hsf1 Expression In Cancer And Evaluating Natural Genetic Variation In Small Molecule Toxicity., Michaela Kendal Foley

Theses and Dissertations

Each year cancer affects nearly 20 million people worldwide and genetic differences across populations can impact cancer onset and progression. Specifically, tumors with high levels of HSF1, the master regulator of the cytoprotective heat shock response (HSR), are correlated with poor patient outcomes in multiple cancers such as prostate, breast, and melanoma. Subsequently, the development of pharmacological inhibitors of HSF1 represents a promising strategy for anticancer therapeutics. Using a luciferase-based transcriptional reporter, two small molecule libraries were screened for inhibitors of HSF1 expression in human embryonic kidney cells, yielding ten compounds that decrease HSF1 expression. To identify if cancer lines …

Leveraging Attention Mechanism To Unlock Gene And Protein Attributes, Ala Jararweh

Computer Science ETDs

Advancing personalized medicine depends on effectively integrating and interpreting the vast, heterogeneous landscape of biological data, from genomic sequences and transcriptomics to the insights embedded in scientific literature. Current machine learning models often focus on single data modalities, limiting their capacity to capture the multifaceted nature of biological systems. We address this gap by developing three attention-based machine-learning models integrating diverse data modalities. Firstly, DeepVul is a multi-task model that leverages cancer transcriptome data to predict genes critical for cancer survival and their corresponding drugs. Subsequently, LitGene refines gene representations by integrating textual information from the scientific literature. Finally, Protein2Text …

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 …

Timigp: A Computational Framework To Determine The Tumor Immune Microenvironment Associated With Prognosis And Immunotherapy Response, Chenyang Li

Dissertations and Theses (Open Access)

Accumulating evidence has suggested that the tumor immune microenvironment (TIME) drastically impacts cancer patients’ clinical outcomes, including prognosis and immunotherapy response. However, understanding TIME remains challenging due to its complexity and heterogeneity. In this dissertation, we introduce TimiGP (Tumor Immune Microenvironment Illustration based on Gene Pairs), a computational framework designed to address this challenge. Leveraging single-cell RNA-seq (scRNA-seq) and bulk gene expression data alongside clinical information, TimiGP constructs a cell-cell interaction network that elucidates the relationship between immune cell function and relevant clinical outcomes, such as prognosis and treatment response. With immunological insights, these cell-cell interactions also facilitate the development …

Early Onset Alzheimer’S Disease Markers In Mouse Hippocampus Unveiled By Single-Cell Transcriptomic Analysis Following Cranial Radiotherapy, Tuba Aksoy

Dissertations and Theses (Open Access)

Cranial radiation therapy plays an integral role in the treatment of brain tumors but can lead to progressive cognitive deficits in survivors by mechanisms that are poorly understood. To develop preventive or mitigative strategies, it is crucial to better understand the underlying pathogenesis of radiation-induced cognitive impairments. The study investigated single-cell transcriptomics and DNA methylation changes as potential drivers of persistent cellular dysfunction after radiation exposure, specifically concentrating on the CA1-3 regions of the hippocampus and the prefrontal cortex due to their role in cognitive functions. Thirteen-week-old mice underwent whole-brain radiation at clinically relevant doses. Following whole-brain radiation, an assessment …

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 …

Optimizing Immunotherapies For Improved Cancer Treatment, Anne Talkington, Anthony Kearsley

Biology and Medicine Through Mathematics Conference

No abstract provided.

Omani Camels From A Cultural And Genomics Perspective, Al Muatasim Al Zadjali

Electronic Theses and Dissertations

The Dromedarian camel, Camelus dromedarius, is native to the Arabian Peninsula, including the Sultanate of Oman. These camels are used for food, milk, as well as show and racing competitions. Despite their economic and cultural importance research on camels in Oman is limited. The goal of this study was to examine their genomic variation, relationship with camels in other parts of the Arabian Peninsula, and to determine if selective breeding has led to the establishment of distinct breeds in Oman. Information was compiled from multiple sources to produce a comprehensive review on the breeding, management, economic and cultural use, …

Epigenetic Modification As A Therapeutic Target In Brafv600e-Mutated Metastatic Colorectal Cancer, Hey Min Lee

Dissertations and Theses (Open Access)

Patients with BRAF^V600E-mutated metastatic colorectal cancer (mCRC) experience a worse prognosis and demonstrate only a 5% response rate to BRAF inhibitor treatment. In this study, adaptive resistance, and a potential combination of standard therapies in BRAF^V600E CRC were unveiled. Intriguingly, a robust association of BRAF^V600E mutation and DNA hypermethylation suggests this is a unique subgroup harboring aberrant epigenetic phenotype. Firstly, DNA methyltransferase (DNMT) inhibitor treatment induced profound DNA hypomethylation in vivo, but minimal change in gene expression due to adaptive elevation of the repressive histone methylation, H3K27me3, leading to compensatory suppression of key tumor suppressor genes, …

The In4mer Crispr/Cas12a Multiplex Knockout Platform And Its Applications, Nazanin Esmaeili Anvar

Dissertations and Theses (Open Access)

Discovering synthetic lethal interactions between genes holds the key to uncovering cancer vulnerabilities, enabling the development of more effective drugs for patients. However, identifying these vulnerabilities in the complex genome of human, which comprises thousands of genes, poses a significant challenge. One alternative approach to investigate these interactions involves exploring enriched sources of synthetic lethal interactions, such as paralog pairs. In recent years, a couple of studies have conducted dual-gene knockout experiments on paralog pairs using different approaches to identify synthetic lethal interactions. In this study, we conducted a meta-analysis of CRISPR genetic interaction screens. We identified a candidate set …

Single Cell Pharmacodynamic Modeling Of Cancer Cell Lines, Arnab Mutsuddy

All Dissertations

Cancer is one of the leading causes of disease related death worldwide. Since the discovery of the genomic origins of cancer, targeted therapy has been developed towards specific mutations implicated for oncogenic transformation. However, current standard-of-care for mapping cancer patients to efficacious drug combination is often inadequate. The pathophysiology of tumor progression relies on the dysregulation of biomolecular pathways of which the topology and the dynamics challenge prognosis. Moreover, the overall genomic instability involved in disease states and the resulting inter-patient as well as intra-tumoral heterogeneity challenge rationalization of therapy and clinical decision-making. It highlights the need for the use …

In Silico Analysis Of C-Type Lectins As Co-Infection Receptors Of Dengue And Chikungunya Viruses In Aedes Aegypti, Munawir Sazali, R. C. Hidayat Soesilohadi, Nastiti Wijayanti, Tri Wibawa, Arif Nur Muhammad Ansori

Makara Journal of Science

Aedes aegypti is a primer vector of dengue virus (DENV) and chikungunya virus (CHIKV). The susceptibility of mosquitoes to DENV and CHIKV depends on their recognition receptor of pathogens. C-type lectins (CTLs) are an important mediator of virus infection in A. aegypti. This study aims to identify potential receptors and determine the binding affinity between ligand–receptor interaction, CTLs and virus envelopes (DENV-1, 2, 3, and 4 and CHIKV) interaction based on in silico analysis. Sample sequences were obtained from GenBank (NCBI), and 10 CTLs were acquired from VectorBase. Homology modeling based on a minimum standard of 20% was processed …

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.

Corals In Crisis: A Transcriptomic Investigation Of Stony Coral Tissue Loss Disease, Kelsey M. Beavers

Biology Dissertations - Archive

Coral reefs face existential threats due to climate change and human activities. The combined effects of ocean warming, overfishing, pollution, and habitat destruction have fundamentally altered the functionality of coral reefs and are driving a drastic increase in the prevalence and severity of coral disease outbreaks. Stony coral tissue loss disease (SCTLD) has emerged one of the most devastating disturbances to Caribbean reef ecosystems on record. Despite notable progress, the cellular mechanisms driving SCTLD pathogenesis remain poorly understood. To address this issue, my dissertation investigates the gene expression, histopathology, immune protein activity, and symbiont community dynamics involved in SCTLD progression …

Exploring 3d Genome Interaction And Epigenetic Regulation Via Swi/Snf Complex And Deep Learning Models, Ruoyun Wang

Dartmouth College Ph.D Dissertations

The three-dimensional organization of the genome is fundamental in regulating gene expression and maintaining cellular function. This organization's complexities, influenced by epigenetic marks and chromatin remodeling complexes, are crucial for understanding genomic regulation. Among these, the SWI/SNF complexes are key, facilitating chromatin accessibility and regulating gene activity across cell types. The first part of my dissertation focuses on SWI/SNF complexes, exploring their role in chromatin remodeling and their impact on 3D genome architecture. Utilizing next-generation sequencing (NGS) techniques, this section investigates the interplay between these complexes and chromatin structure. During my research on the SWI/SNF complex, I was intrigued by …

Identifying New Cancer Genes Based On The Integration Of Annotated Gene Sets Via Hypergraph Neural Networks, Chao Deng, Hong-Dong Li, Li-Shen Zhang, Yiwei Liu, Yaohang Li, Jianxin Wang

Computer Science Faculty Publications

Motivation

Identifying cancer genes remains a significant challenge in cancer genomics research. Annotated gene sets encode functional associations among multiple genes, and cancer genes have been shown to cluster in hallmark signaling pathways and biological processes. The knowledge of annotated gene sets is critical for discovering cancer genes but remains to be fully exploited.

Results

Here, we present the DIsease-Specific Hypergraph neural network (DISHyper), a hypergraph-based computational method that integrates the knowledge from multiple types of annotated gene sets to predict cancer genes. First, our benchmark results demonstrate that DISHyper outperforms the existing state-of-the-art methods and highlight the advantages of …

Sccad: Cluster Decomposition-Based Anomaly Detection For Rare Cell Identification In Single-Cell Expression Data, Yunpei Xu, Shaokai Wang, Qilong Feng, Jiazhi Xia, Yaohang Li, Hong-Dong Li, Jianxin Wang

Computer Science Faculty Publications

Single-cell RNA sequencing (scRNA-seq) technologies have become essential tools for characterizing cellular landscapes within complex tissues. Large-scale single-cell transcriptomics holds great potential for identifying rare cell types critical to the pathogenesis of diseases and biological processes. Existing methods for identifying rare cell types often rely on one-time clustering using partial or global gene expression. However, these rare cell types may be overlooked during the clustering phase, posing challenges for their accurate identification. In this paper, we propose a Cluster decomposition-based Anomaly Detection method (scCAD), which iteratively decomposes clusters based on the most differential signals in each cluster to effectively separate …