Systems Biology Commons^™

Integration Of Multi-Omics Datasets Evaluating Structural And Functional Features Of The Gut Microbiome In People With Hiv (Pwh)., Aakarsha Vijayakumar Rao

Electronic Theses and Dissertations

Gut dysbiosis characterized by reduced abundance of beneficial butyrate-producing bacteria has been independently linked to HIV-1 infection and heavy alcohol drinking. Further, gut dysbiosis results in loss of gut barrier integrity, microbial translocation and host-specific systemic inflammation. Therefore, to evaluate the functional consequences of structural changes in the gut microbiome, integrated data analysis is imperative. In this dissertation, we perform integrated analyses using data from multi-omics platforms to examine the structural and functional features of the gut microbiome of PWH. Gut microbiome composition was evaluated by sequencing V4 region of 16S rDNA, concentrations of metabolites and host-specific immune markers were …

Identifying And Characterizing Transition Cells In Developmental Processes From Scrna-Seq Data, Yuanxin Wang

Dissertations and Theses (Open Access)

During the development of multicellular organisms, individual cells make distinct decisions about their cell types and states. Understanding the molecular mechanisms underlying cellular state transitions at different developmental stages provides deep insights into physiology, morphology and the etiology of diseases. Single-cell RNA-sequencing (scRNA-seq), which is widely used to study complex cell states and dynamic gene expression patterns, enables us to investigate molecular mechanisms of cellular state transitions. Currently, however, computational tools available for identifying cellular states and state transitions remain limited.

Although trajectory-based methods such as Monocle and Slingshot assume that state transitions generate continuous expression profiles, they cannot distinguish …

Emergence Of Heterogeneity In Bacteria During Antibiotic Exposures, Mirjana Stevanovic

Dartmouth College Ph.D Dissertations

Bacterial populations exposed to antibiotics often exhibit phenotypic heterogeneity, with individual cells displaying distinct responses with fates ranging from survival to arrest or death. The emergence of this heterogeneity is largely driven by feedback mechanisms mediated by the interactions between antibiotic action, gene regulation, and cellular metabolism. These responses unfold in dynamic environments where conditions such as nutrient availability and drug concentration fluctuate over time and space. Yet, these complex interactions and their role in shaping population-level outcomes during drug responses remain poorly understood. Using tetracycline resistance in E. coli as a model system, this thesis focuses on how these …

Hierarchical Lineage Tracing To Unravel Mechanisms Of Cancer Treatment Resistance, Rachel Danielle Saxe

Dartmouth College Ph.D Dissertations

Cancer cells adapt to treatment, leading to the emergence of clones that are more aggressive and resistant to anti-cancer therapies. We have a limited understanding of the development of treatment resistance as we lack technologies to map the evolution of cancer under the selective pressure of treatment. To address this, we developed a hierarchical, dynamic lineage tracing method called FLARE (Following Lineage Adaptation and Resistance Evolution). We use this technique to track the progression of acute myeloid leukemia (AML) cell lines through exposure to Cytarabine (AraC), a front-line treatment in AML, in vitro and in vivo. We map distinct cellular …

Metabolite Analysis To Understand Factors Limiting Microbial Fermentation At High Substrate Concentrations, Bishal D. Sharma

Dartmouth College Ph.D Dissertations

Clostridium thermocellum, a thermophilic anaerobic bacterium, holds promise as a biocatalyst for conversion of lignocellulosic biomass into biofuels. This microbe has been subjected to various metabolic engineering strategies, including the deletion of genes encoding secondary fermentation products such as H₂, formate, acetate, and lactate, as well as the expression of heterologous genes to redirect carbon flux toward ethanol production. Despite these efforts, achieving economically viable ethanol titers remains a challenge. We hypothesized that studying how intracellular metabolite concentrations change as fermentation stops could reveal metabolic bottlenecks or regulatory mechanisms limiting ethanol production at high titers. However, metabolomics studies at …

Regeneration In Planarians Modifies Behavioral Switching, N. S. Tellakula, Eva-Maria S. Collins, W. B. Kristan Jr.

Biology Faculty Works

The planarian Dugesia japonica responds differently to localized stimuli: anterior regions turn, middle regions elongate, and posterior regions contract. If cut into several pieces, each piece immediately produces the same three responses. Over several days, each piece regenerates all transected body parts. This study tested how the pieces coordinate behavioral responses during regeneration. We first determined the locations of the turning/elongation and elongation/contraction behavioral switches. Immediately, all transections moved both switching sites away from the cut sites so that the worm pieces produced the same three responses as intact worms. During regeneration, the sites of behavioral switching moved progressively closer …

Trpv1 And Its Co‑Expressed Genes Are Associated With The Progression Of Hepatocellular Carcinoma, Bhuvnesh P. Sharma, Himanshu N. Singh, Sanjay Kumar, Deepak Verma, Deepak Parashar, Murali M. Yallapu, Everardo Cobos, Subhash C. Chauhan, Vivek K. Kashyap

Research Symposium

Background: Hepatocellular carcinoma (HCC) is the most common type of liver cancer. Transient receptor potential vanilloid 1 (TRPV1) is a nonselective Ca²⁺ channel protein widely expressed and plays a significant role in cancer initiation and progression. However, the biological significance of TRPV1 in HCC has not been systematically and comprehensively investigated. This study used deep data mining and transcriptomics analyses to describe the significance of TRPV1 expression and its association with HCC prognosis.

Methods: Download the RNA expression of TRPV1 from the Cancer Genome Atlas (TCGA), Genotype Tissue Expression Atlas (GTEx), Tumor Immune Estimation Resource (TIMER), and the UALCAN …

The Correlation Between Temporomandibular Disorder (Tmd) And Vitamin D Deficiency, Iris Kim, Claudia Freitas

Annual Research Symposium

No abstract provided.

Identification Of Novel Genetic Biomarkers Linked To The Prodromal Stage Of Parkinson’S Disease (Pd) Patients, Marwa Tawfik Badawy

Theses and Dissertations

Background and Objective: The early diagnosis of neurodegenerative diseases, such as Parkinson's disease (PD), is particularly challenging because symptoms appear only after significant neuronal damage has already occurred. This study is utilizing variant call format (VCF) analysis to identify genetic variants and novel genes that could serve as early prognostic markers for prodromal PD. Materials and Methods: Data were sourced from the Parkinson's Progression Markers Initiative (PPMI), focusing on prodromal patients with gVCF data from the 2021 cohort. The study included 304 participants, comprising 100 healthy controls, 146 individuals with prodromal genetic indicators, 21 individuals with prodromal hyposmia, and 37 …

Taming Biological Complexity Through The Use Of Symmetries, Luis A. Álvarez-García

Dissertations, Theses, and Capstone Projects

The study of biological systems is, inherently, the study of very complex systems. This is essentially due to the fact that they are made up of numerous, often very complicated, interactions between an extensive number of components. Often necessitating an abundance of quantitative parameters and details for a precise description. The human brain for ex- ample, consisting of ∼ 80 billion neurons with ∼ 800 to 100 trillion connections between them, each of them depending on a large set of parameters. Even simpler examples such as bacterial organisms, such as E. coli and B. subtilis, which we focus on …

Genome-Wide Profiling Of Trna Modifications By Induro-Trnaseq Reveals Coordinated Changes, Yuko Nakano, Howard Gamper, Henri Mcguigan, Sunita Maharjan, Jiatong Li, Zhiyi Sun, Erbay Yigit, Sebastian Grünberg, Keerthana Krishnan, Nan-Sheng Li, Joseph Piccirilli, Ralph Kleiner, Nicole Nichols, Brian Gregory, Ya-Ming Hou

Department of Biochemistry and Molecular Biology Faculty Papers

While all native tRNAs undergo extensive post-transcriptional modifications as a mechanism to regulate gene expression, mapping these modifications remains challenging. The critical barrier is the difficulty of readthrough of modifications by reverse transcriptases (RTs). Here we use Induro-a new group-II intron-encoded RT-to map and quantify genome-wide tRNA modifications in Induro-tRNAseq. We show that Induro progressively increases readthrough over time by selectively overcoming RT stops without altering the misincorporation frequency. In a parallel analysis of Induro vs. a related RT, we provide comparative datasets to facilitate the prediction of each modification. We assess tRNA modifications across five human cell lines and …

An Agent-Based Model Of Microglia And Neuron Interaction: Implications In Neurodegenerative Disease, Cheyenne Ty, Amanda Case, Emmanuel Mezzulo, Abigail Penland, Kamila Larripa

Spora: A Journal of Biomathematics

Whether immune cells protect or harm the brain is an open question depending on context, and their role is implicated in multiple diseases such as Alzheimer's disease, dementia, and other neurological disorders. Microglia, a specific type of immune cell in the central nervous system, play a key role in homeostasis, and genes associated with an elevated risk of Alzheimer's disease correspond with deficiencies in their behavior. We created an agent-based model that incorporates inflammatory signaling, chemotaxis, and phagocytosis of damaged neurons and allows the exploration of crucial pathways in the maintenance of brain health. We specifically investigated pathways related to …

From Sampling To Simulating: Single-Cell Multiomics In Systems Pathophysiological Modeling, Alexandra Manchel, Michelle M. Gee, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

As single-cell omics data sampling and acquisition methods have accumulated at an unprecedented rate, various data analysis pipelines have been developed for the inference of cell types, cell states and their distribution, state transitions, state trajectories, and state interactions. This presents a new opportunity in which single-cell omics data can be utilized to generate high-resolution, high-fidelity computational models. In this review, we discuss how single-cell omics data can be used to build computational models to simulate biological systems at various scales. We propose that single-cell data can be integrated with physiological information to generate organ-specific models, which can then be …

The Mayfly Newsletter, Donna Giberson

The Mayfly Newsletter

The Mayfly Newsletter is the official newsletter of the Permanent Committee of the International Conferences on Ephemeroptera.

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 …

Tissue Proteomics Of Feline Mammary Carcinoma: Identification Of Potential Biomarkers Based On Metastatic Status And Histopathological Characteristics, Weejarin Paphussaro, Sittiruk Roytrakul, Narumon Phaonakrop, Sawanya Charoenlappanit, Anudep Rungsipipat, Theerawat Tharasanit, Gunnaporn Suriyaphol Assoc. Prof.

The Thai Journal of Veterinary Medicine

Feline mammary carcinoma (FMC) is a prevalent and aggressive cancer with high metastatic potential. Few tissue biomarkers have been reported to help evaluate disease progression in FMC. This study aimed to analyze the tissue proteomic profiles of metastatic feline mammary carcinoma (mFMC) and non-metastatic FMC (NmFMC) across various histological grades (HGs) and histological types (HTs) using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Tissue samples were collected from 13 NmFMC, 26 mFMC and 13 healthy controls (CTRL). Samples were trypsinized and subjected to LC-MS/MS. Proteome results were analyzed based on the metastatic status, HGs and HTs of the samples. The findings revealed …

Leveraging Quantitative Systems Pharmacology For Dose Optimization In Oncology Drug Development, Blerta Shtylla

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Kreig: Quantifying The Relationship Between Sars-Cov-2 Viral Load And Infectiousness, Aurelien Marc

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Study Of Different Treatment Strategies In Epidemic Models Using Nonlinear Model Predictive Control, Hector Puebla, Luis A. Ricardez-Sandoval, Priti Kumar Roy

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Modelling Saccharomyces Cerevisiae For The Production Of Fermented Beverages, Paul A. Valle Dr., Yolocuauhtli Salazar Dr., Luis N. Coria Dr., Oscar N. Soto Dr., Jesus B. Paez Dr.

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.