Systems Biology Commons^™

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.

Serum Proteomic Profile Of Subclinical Babesia Bovis Infection In Pcr-Positive Eld's Deer Using Serum Protein Electrophoresis Coupled With Lc-Ms/Ms, Vichayanee Pumpitakkul, Sittiruk Roytrakul, Narumon Phaonakrop, Gunnaporn Suriyaphol Assoc. Prof.

The Thai Journal of Veterinary Medicine

Subclinical babesiosis observed in captive Eld’s deer, which act as reservoirs for ticks, poses a risk to healthy herds. However, the knowledge of biomarkers for subclinically infected Eld’s deer and host-parasite interactions is limited. This study aimed to investigate the serum proteomic profiles and protein interactions of Babesia bovis and subclinically infected Eld’s deer, PCR-positive for B. bovis, using automated serum protein electrophoresis and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The findings revealed albumin and four globulin fractions: alpha-1, alpha-2, beta, and gamma globulin. Albumin protein (ALB) was consistently detected across all fractions, highlighting its role in maintaining osmotic balance …

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 …

Computational Drug Repositioning And 3d Skin-Like Tissues Identify Anti-Fibrotic Targets For Systemic Sclerosis (Ssc), Dillon Popovich

Dartmouth College Ph.D Dissertations

Systemic Sclerosis (SSc) is a rare autoimmune disease characterized by dermal and internal organ fibrosis, including heart, lungs, and gastrointestinal tract, and autoantibody formation. Although disease etiology is currently unknown, like other autoimmune diseases, SSc likely develops due to environmental factor exposure in genetically susceptible individuals. Fibrotic diseases are notoriously difficult to treat. Coupled with the autoimmune aspect, SSc is difficult to study scientifically due to the lack of complex disease models that can recapitulate the immune-fibrotic axis of the disease. Due to this, there are only two FDA approved medical treatments for SSc approved for symptomatic treatment of SSc …

Dynamic Metabolic Flux Analysis Amidst Data Variability: Sphingolipid Biosynthesis Case Study In Arabidopsis Thaliana Cell Cultures, Abraham Boluwatife Osinuga

Department of Chemical and Biomolecular Engineering: Dissertations, Theses, and Student Research

Sphingolipids are pivotal for plant development and stress responses. Growing interest has been directed towards fully comprehending the regulatory mechanisms of the sphingolipid pathway. In this study, we explore its de novo biosynthesis and homeostasis in Arabidopsis thaliana cell cultures, shedding light on fundamental metabolic mechanisms. Employing ¹⁵N isotope labeling and quantitative dynamic modeling approach, we obtained data with notable variations and developed a regularized and constraint-based Dynamic Metabolic Flux Analysis (r-DMFA) framework to predict metabolic shifts due to enzymatic changes. Our analysis revealed key enzymes such as sphingoid-base hydroxylase (SBH) and long-chain-base kinase …

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.

Sircling The Cquare, Latika Balachander

Masters Theses

As we journey into an increasingly virtual and intangible reality, is there an opportunity for our tactile fabrics to journey with, and even reorient us? Can they exist in our future worlds to remind us of the value of current traditional, low-tech practices that we may soon forget?

Referencing the fundamental fabric languages of knitted and woven structures, this collection of garments, that I term “Earthsuits,” embody the stages of metamorphosis as we adjust to a new phase of our perceptive reality. With an emphasis on circling, we loop through virtual squares like screens and pixels, to the circles of …

Quantitative Proteomic Strategies To Determine Substrate Specificities Of Phosphoprotein Phosphatases, Hieu Trung Nguyen

Dartmouth College Ph.D Dissertations

Reversible phosphorylation is a crucial regulatory mechanism of cellular signaling pathways. Being the most prevalent post-translational modification (PTM) in the cells, with over 75% of all proteins detected to be phosphorylated, phosphorylation regulates a significant number of important cellular processes that have implications in various diseases. Phosphorylation is carried out by protein kinases, which have been extensively studied. However, the opposite reaction, carried out by protein phosphatases, has lagged significantly, exposing a gap of knowledge that is required to be investigated to delineate the kinase-substrate-phosphatase relationship. Phosphoprotein phosphatase family (PPPs), containing seven members of phospho-Serine (pS) and phospho-Threonine (pT) phosphatases, …

How Neurobehavior And Brain Development In Alternative Whole-Organism Models Can Contribute To Prediction Of Developmental Neurotoxicity, Eva-Maria S. Collins, E. V. S. Hessel, S. Hughes

Biology Faculty Works

No abstract provided.

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 …

Cytokine Activity Estimation And Receptor Abundance Approximation With Multimodal Scrna-Seq/Cite-Seq Data., Azka Javaid

Dartmouth College Ph.D Dissertations

Single-cell RNA-sequencing (scRNA-seq) data enables individual cell resolution quantification of messenger RNA. While revolutionary for revealing key cell type and cell phenotype-specific heterogeneity, scRNA-seq data has important statistical challenges. First, scRNA-seq data is usually more sparse and second, it is more variable than bulk transcriptomics data. Given these challenges, more intuitive and interpretive statistical and computational methods are needed to develop appropriate solutions. Here, we detail the development of three techniques to perform receptor abundance estimation and cytokine activity estimation for scRNA-seq data. While SPECK (Surface Protein abundance Estimation using CKmeans-based clustered thresholding) and STREAK (gene Set Testing-based Receptor abundance …

Ordinal-Level Biomass Of Insects Collected On And Off Prairie Dog Colonies, Colby Cook, Chad Zerr, Lorelei E. Patrick

SACAD: Scholarly Activities

Ordinal-level Biomass of Insects Collected On and Off Prairie Dog Colonies

Colby Cook, Chad Zerr, and Lorelei Patrick

Recent work has shown that bats in Colorado and Kansas are more active over prairie dog colonies. It is hypothesized that the reason for this is increased abundance and richness of insects found on colonies versus off colonies. Sampling from 2022 indicated that insect biomass was not different between location types, but suggested that the relative abundance of insect orders may differ. Additional insect sampling was conducted in 2023. Light traps were deployed on the same nights, one on a prairie dog …

Targeting Cholinergic Signaling In Glioblastoma, Sumyuktha Vijay Anand

Dartmouth College Ph.D Dissertations

Primitive stem cell-like populations that are prone to malignant transformation reside in the brain throughout adulthood. My lab’s reports and many others have characterized subsets of glioma cells reminiscent of adult stem-like cells implicating them rational candidates for cell-targeted therapies. Emerging evidence suggests that the neurotransmitter microenvironment influences these stem-like cells during glioma progression providing an inroad to study neuromodulators in glioma. Some glioma stemlike cells share characteristics with adult tissue oligodendrocyte progenitor cells. Primitive cells of the oligodendroglial lineage express muscarinic acetylcholine receptors (mAChRs), and their “stemness” is maintained by the acetylcholine (ACh) neurotransmitter. Here, I conduct transcriptomic, electrophysiological, …

Univariate And Multivariate Approaches For Identifying Key Differential Volatile Compounds In Wedelia Trilobata Essential Oils From Four Different Locations, Tuan Ashraf Faiz Tuan Anuar, Suria Ramli, Chamroon Laosinwattana, Kamalrul Azlan Azizan

Makara Journal of Science

Geographical location is an important factor affecting the production of the volatile compounds and corresponding bioactivity of essential oil (EO). The aim of this study was to determine whether the bioactivity of Wedelia trilobata EO varies by geographical location and identify the key volatile compounds involved in bioactivity. A total of 95 volatile compounds reported in W. trilobata EOs obtained from Brazil, India, Malaysia and Thailand were retrieved from the literature, and changes and key differential volatile compounds were identified with univariate and multivariate methods. Results showed that the monoterpene hydrocarbon content of α-phellandrene and α-pinene were higher than that …

Investigating The Protein Interactome Of Escherichia Coli To Understand Metabolic Regulation When Proteins Bind: A Systems Biology Study., Shomeek Chowdhury

Theses and Dissertations

Proteins bind other proteins and work together as machines to perform many biological functions. Metabolic enzymes governing the life-sustaining metabolic reactions and therefore, metabolism are proteins which also binds other proteins. In this dissertation work, I have explored proteins when they interact with metabolic enzymes, play any role in regulating the cell’s metabolism. I study this phenomenon in Escherichia coli whose protein-protein interaction data is readily available in public databases with proper reference to the experimental study. Another good reason is the predictions we make in this computational study can be tested and validated in E. coli as it is …

Mathematical Modeling And Analysis Of Inflammation And Tissue Repair: Lung Inflammation And Wound Healing In Corals Under Stress, Quintessa Hay

Theses and Dissertations

A variety of insults, including tissue injury and/or exposure to pathogen, elicit an immune response in many organisms. An improperly regulated immune response can result in deleterious effects to the organism. Here we present models for lung injury in young and old mice and models for wound healing in coral reefs.

It is well known that the immune response becomes less effective in older individuals. This is of particular interest in pulmonary insults such as ventilator induced lung injury (VILI) or lung infection. We extended a mathematical model for the inflammatory response to VILI and used experimental data to select …

Leveraging Redundancy As A Link Between Spreading Dynamics On And Of Networks, Felipe Xavier Costa

Electronic Theses & Dissertations (2024 - present)

A constant quest in network science has been in the development of methods to identify the most relevant components in a dynamical system solely via the interaction structure amongst its subsystems. This information allows the development of control and intervention strategies in biochemical signaling and epidemic spreading. We highlight the relevant components in heterogeneous dynamical system by their patterns of redundancy, which can connect how dynamics affect network topology and which pathways are necessary to spreading phenomena on networks. In order to measure the redundancies in a large class of empirical systems, we develop the backbone of directed networks methodology, …

Wildfires Are Burning Less Frequently And More Severely Than Historically In The Western Us: A Novel Approach To Calculating Fire-Regime Departures, Jeffrey Ryan Chandler

Graduate Student Theses, Dissertations, & Professional Papers

Changing climate, vegetation, and fire exclusion are altering and homogenizing fire-regime attributes compared to historic conditions. Fire-regime changes are commonly quantified using departure metrics, which are often based on measures of central tendency (i.e. changes in the mean). These metrics can mischaracterize complex changes to the distributional characteristics of fire-regime attributes. Here we develop a fire-regime departure metric that quantifies nonparametric distributional changes to fire-regime attributes over time. We use this metric to compare fire frequency and severity between historical (~1600-1880) and contemporary (1880- 2021) time periods in western US forests. Our analysis revealed that 89% of Western US forests …