Systems Biology Commons^™

Individualized Bayesian Inference Identifies Novel Genetic Variants For Parkinson's Disease, Jin Ren, Yasaman J. Soofi, Md Asad Rahman, Qing Lu, Jinling Liu

Engineering Management and Systems Engineering Faculty Research & Creative Works

Parkinson's disease (PD) is a complex neurodegenerative disorder with a significant genetic component. While genome-wide association studies (GWAS) have been instrumental in identifying genetic variants associated with PD, the reliance on large sample sizes and population-level analyses may overlook variants with lower minor allele frequencies or individual-specific relevance. Individualized Bayesian Inference (IBI) offers a promising method to complement GWAS by identifying and prioritizing candidate genetic markers at both the individual and patients-like-me subgroup levels. This study evaluates the application of IBI to PD genetics, using GWAS as a baseline for comparison. We analyzed genetic data from the Fox Insight online …

From Fair To Cure: Guidelines For Computational Models Of Biological Systems, Herbert M. Sauro, Eran Agmon, Michael L. Blinov, John H. Gennari, Joseph L. Hellerstein, Adel Heydarabadipour, Bartholomew E. Jardine, Elebeoba May, David P. Nickerson, Lucian P. Smith, Gary D. Bader, Frank T. Bergmann, Patrick M. Boyle, Andreas Dräger, James R. Faeder, Song Feng, Juliana Freire, Fabian Fröhlich, James A. Glazier, Thomas E. Gorochowski, Tomas Helikar, Henning Hermjakob, Stefan Hoops, Peter Hunter, Princess I. Imoukhuede, Sarah M. Keating, Matthias König, Reinhard Laubenbacher, Leslie M. Loew, Carlos F. Lopez, William W. Lytton, Rahuman S. Malik-Sheriff, Andrew Mcculloch, Pedro Mendes, Lealem Mulugeta, Chris J. Myers, Jerry G. Myers, Anna Niarakis, David D. Van Niekerk, Brett G. Olivier, Alexander A. Patrie, Ellen M. Quardokus, Nicole Radde, Johann M. Rohwer, Sven Sahle, James C. Schaff, Falk Schreiber, T. J. Sego, Janis Shin, Jacky L. Snoep, Rajanikanth Vadigepalli, H. Steven Wiley, Dagmar Waltemath, Ion I. Moraru

Computational Medicine Center Faculty Papers

Guidelines for managing scientific data have been established under the FAIR principles, requiring that data be Findable, Accessible, Interoperable, and Reusable. In many scientific disciplines, especially computational biology, both data and models are key to progress. For this reason, and recognizing that such models are a very special type of "data", we argue that computational models, especially mechanistic models prevalent in medicine, physiology and systems biology, deserve a complementary set of guidelines. We propose the CURE principles, emphasizing that models should be Credible, Understandable, Reproducible, and Extensible. We delve into each principle, discussing verification, validation, and uncertainty quantification for model …

Red Midge Larvae Are An Invertebrate Alternative Diet To Beef Liver For Planarian Husbandry, Jonah Pacis , '25, Danielle Ireland, Evangeline Coffinas, Jerome Sheehan, Kate Sun , '27, Eva-Maria S. Collins

Biology Faculty Works

Freshwater planarians are an emerging model for toxicology and neuroscience because of their amenability to rapid behavioral screening and remarkable ability to regenerate a cephalized nervous system. As invertebrates, planarians can help reduce the use of vertebrates in research; however, laboratories typically maintain planarians on diets of homogenized organic beef or chicken liver, raising ethical concerns with feeding a vertebrate diet. Organic liver is difficult to obtain, and preparation methods vary, introducing intra- and interlaboratory variability. Here, we show that Dugesia japonica planarians can be maintained for over a year on commercially available red midge larvae (RML), a natural prey …

The Brain-Derived Neurotrophic Factor (Bdnf) And Its Importance To Organism Survival And Development, Christopher Monnett Smith

Holster Scholar Projects

Brain-Derived Neurotrophic Factor (BDNF) has been the subject of numerous studies regarding the functioning of the brain in relation to topics such as neural plasticity and neural survival. However, BDNF has also been implicated in the induction of changes not only in neural tissue but multiple other tissue types across the human body. The aim of this literature review is to provide a comprehensive, yet brief, overview of BDNF’s influence on the functioning of the nervous, cardiovascular, respiratory, muscular, and immune systems.

The Science Of Sound: Studying The Cognitive, Emotional, And Physiological Effects Of Frequency, Genre, And Music, Jett Yarborough

Senior Honors Theses

Music influences emotion, physiology, and cognition, yet little is known about how the frequency it is tuned to affects these influences. Prior research has shown that music tuned to 432 Hz can reduce stress, lower blood pressure, and improve sleep. My colleagues and I conducted two studies to investigate this. Our research found that music tuned to 432 Hz promotes a significant increase in memory retention and induces a state of focus and relaxation. These results suggest that shifting from the standard tuning frequency of 440 Hz to 432 Hz could have a profoundly positive impact on our daily lives. …

Ibi-Dt: A Novel Approach Combining Individualized Bayesian Inference And Decision Tree For Identifying Cancer Drivers And Their Interactions, Md Asad Rahman, Gregory F. Cooper, Jinying Zhao, Xinghua Lu, Jinling Liu

Engineering Management and Systems Engineering Faculty Research & Creative Works

Cancer is mainly caused by a relatively small portion of somatic genome alterations (SGAs), called cancer drivers. Despite success in identifying a good number of cancer drivers, many more remain to be discovered to explain various cancers. Moreover, limited tools are available to identify potential interactions among cancer drivers for a better understanding of oncogenesis. To tackle these challenges, we have developed a novel approach called individualized Bayesian inference using a decision tree (IBI-DT). IBI-DT recognizes the genetic heterogeneity among cancer patients, where different individuals or patient subgroups of distinct genomic makeup may have different drivers. IBI-DT works by constructing …

Statistical Analysis Of Multi-Endpoint Phenotypic Screening Increases Sensitivity Of Planarian Neurotoxicity Testing, Danielle Ireland, L. J. Word, Eva-Maria S. Collins

Biology Faculty Works

There is an urgent need for high-throughput screening (HTS) models to replace, refine, and/or reduce (“3Rs”) vertebrate toxicity testing. Replacing in vivo animal studies is challenging for neurotoxicity and developmental neurotoxicity (DNT), where the functional relevancy of adverse outcomes needs to be assessed on the whole organism. We previously screened the NTP 87-compound library (NTP87), consisting of known and suspected developmental neurotoxicants, and showed that planarian HTS can identify known (developmental) neurotoxicants. Because analysis methods can impact screening results, and our original analysis used the lowest-observed-effect-level (LOEL) only, we hypothesized that the use of state-of-the-art statistical analysis would increase the …

Variation In Phenotype, Genotype, And Somatic Diversity Among Asexual Schmidtea Mediterranea Planarians, S. Kershenbaum, Danielle Ireland, Ziad Sabry , '20, Christina Rabeler, Vir Shetty , '22, A. Aboobaker, Eva-Maria S. Collins

Biology Faculty Works

Most multicellular life reproduces sexually, utilizing a single-celled stage that acts as a genetic bottleneck. This bottleneck limits the evolution of selfish cell adaptations by ensuring all cells descend from a single progenitor. We investigated an obligately asexual strain of Schmidtea mediterranea planarians that reproduces by self-bisection and lacks a single-cell bottleneck. Using 2.5 yearlong data on planarian reproductive behavior combined with genotyping, we revealed two previously undescribed genetically distinct substrains within the CIW4 strain. One substrain showed reduced fitness, which correlated with substantial losses of heterozygosity and increased somatic diversity. By genotyping consecutive head offspring over multiple generations, we …

Using Published Undergraduate Biomechanics Research On Hydra Mouth Opening To Train Undergraduates, Stephen Hackler, T. Goel, Jonah Pacis , '25, Eva-Maria S. Collins

Biology Faculty Works

Biophysics research is exciting because physical approaches to biology can provide novel insights, and it is challenging because it requires knowledge and skills from multiple disciplines. We have developed an undergraduate biophysics laboratory module that teaches fundamental skills such as time-lapse microscopy, image analysis, programming, critical reading of scientific literature, and basics of scientific writing and peer review. The module is accessible to students who are familiar with introductory statistics, cell biology, and differential calculus. We used published research on the biomechanics of Hydra mouth opening as a framework because it describes a stunning biological phenomenon: Hydra, a freshwater …

Catching A Fever: A Comparison Of Vachellia Xanthophloea Populations In The Limpopo And Luvuvhu River Floodplains Of The Makuleke Contractual Park, Kianie B. David

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

This study investigates patterns of stand structure regeneration, growth characteristics, and coarse woody debris (CWD) patterns in Vachellia xanthophloea (fever tree) stands within the Makuleke Contractual Park (MCP), a semi-arid savanna system in northern Kruger National Park (KNP), South Africa. Fieldwork was conducted across two stand types: a monospecific fever tree stand in Rietbok Vlei and a mixed-species stand in the Western Nhlangaluwe Floodplain where fever tree is established with Faidherbia albida (ana tree). Data were collected from 20 total 1/4-acre (1,011 m²) circular plots between both stands in 2024 and 2025, including seedling root collar diameter (RCD), …

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 …

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 …

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 …

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 …

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.

Protocol For An Agent-Based Model Of Recombination In Bacteria Playing A Public Goods Game, Isaiah Paolo A. Lee, Omar T. Eldakar, J. Peter Gogarten, Cheryl P. Andam

Biology Faculty Articles

Agent-based models are composed of individual agents coded for traits, such as cooperation and cheating, that interact in a virtual world based on defined rules. Here, we describe the use of an agent-based model of homologous recombination in bacteria playing a public goods game. We describe steps for software installation, setting model parameters, running and testing models, and visualization and statistical analysis. This protocol is useful in analyses of horizontal gene transfer, bacterial sociobiology, and game theory.

For complete details on the use and execution of this protocol, please refer to Lee et al.¹

The Persistence Of Blue Ash In The Aftermath Of Emerald Ash Borer May Be Due To Adult Oviposition Preferences And Reduced Larval Performance, Don Cipollini, Emily Morton

Biological Sciences Faculty Publications

1. We examined the health of mature blue ash, Fraxinus quadrangulata, in two forests in southwestern Ohio in relation to that of mature white ash, F. americana, and examined the potential importance of oviposition preferences and larval resistance in the persistence of blue ash.
2. Both blue ash and white ash were largely unaffected by emerald ash borer in 2012. By 2018, nearly 90% of the blue ash trees observed in these forests had full or nearly full canopies, as opposed to less than 20% of the white ash encountered in our studies. In 2021, blue ash maintained a …

Shedding Light On Cellular Glycolysis Pathway Kinetics: Combining Kinetic, Mechanistic Modelling Approaches With Label Free Microspectroscopic Imaging. (Cytomechspec), Nitin Patil

Articles

Glycolysis pathway kinetics in cells are known to be modulated for several disorders (cancers, neurodegenerative disorders, diabetes, etc.) and are currently been targeted as a biomarker for disease diagnostics and therapy. Although there are several approaches for monitoring the pathway kinetics, ranging from simple kinetic biochemical assays to sophisticated omics techniques, there remains a significant gap in the field, as there is a noticeable compromise between the extent of insights achievable from approaches which are destructive to the sample, and the real-time, kinetic analysis of a system.

Vibrational spectroscopy is a powerful, label-free, non-invasive tool capable of sub-cellular resolution, the …

Homeostatic Synaptic Plasticity Of Miniature Excitatory Postsynaptic Currents In Mouse Cortical Cultures Requires Neuronal Rab3a, Andrew G. Koesters, Mark M. Rich, Kathrin L. Engisch

Biological Sciences Faculty Publications

Following prolonged activity blockade, amplitudes of miniature excitatory postsynaptic currents (mEPSCs) increase, a form of homeostatic plasticity termed “synaptic scaling.” We previously showed that a presynaptic protein, the small GTPase Rab3A, is required for full expression of the increase in miniature endplate current amplitudes following prolonged blockade of action potential activity at the mouse neuromuscular junction in vivo (Wang et al., 2011), but it is unknown whether this form of Rab3A-dependent homeostatic plasticity shares any characteristics with central synapses. We show here that synaptic scaling of mEPSCs is impaired in mouse cortical neuron cultures prepared from Rab3A-/- and Rab3A Earlybird …

Long-Term Spring Through Fall Capture Data Of Eptesicus Fuscus In The Eastern Usa Before And After White-Nose Syndrome, Molly Simonis, Lynn K. Hartzler, Joshua Campbell, Timothy C. Carter, Lisa Noelle Cooper, Katelin Cross, Katherine Etchison, Traci, R. Andrew King, Richard J. Reynolds, Yasmeen Samar, Michael Yasmeen, Sarah Stankavich, Gregory G. Turner, Megan A. Rúa

Biological Sciences Faculty Publications

Emerging infectious diseases threaten wildlife populations. Without well monitored wildlife systems, it is challenging to determine accurate population and ecosystem losses following disease emergence. North American temperate bats present a unique opportunity for studying the broad impacts of wildlife disease emergence, as their federal monitoring programs were prioritized in the USA throughout the 20 th century and they are currently threatened by the invasive fungal pathogen, Pseudogymnoascus destructans ( Pd ), which causes white-nose syndrome. Here we provide a long-term dataset for capture records of Eptesicus fuscus (big brown bat) across the eastern USA, spanning 16 years before and 14 …

Gabaergic Synaptic Scaling Is Triggered By Changes In Spiking Activity Rather Than Transmitter Receptor Activation, Carlos Gonzalez-Islas, Zahraa Sabra, Ming-Fai Fong, Pernille Bülow, Nicholas Au Yong, Kathrin Engisch, Peter Wenner

Biological Sciences Faculty Publications

Homeostatic plasticity represents a set of mechanisms that are thought to recover some aspect of neural function. One such mechanism called AMPAergic scaling was thought to be a likely candidate to homeostatically control spiking activity. However, recent findings have forced us to reconsider this idea as several studies suggest AMPAergic scaling is not directly triggered by changes in spiking. Moreover, studies examining homeostatic perturbations in vivo have suggested that GABAergic synapses may be more critical in terms of spiking homeostasis. Here we show results that GABAergic scaling can act to homeostatically control spiking levels. We find that increased or decreased …

Ethical Considerations Of Clinical Research In Emergency Care Settings: A Review, Adith Velavan

Honors Scholar Theses

Emergency and acute care settings are some of the most volatile and high intensity areas of any healthcare operation. Better understanding of systems and treatments in these spaces are critical to improving outcomes for the high risk patients that are treated there. Clinical research serves as a cornerstone of modern medical research, and is critical to the further improvement of clinical care in these settings. This thesis serves to explore the ethicality of such research given the constraints of emergency medicine settings. Not only does this thesis provide a strong foundation regarding the history and current practices of clinical research, …

Developmental Exposure To Corn Grown On Lake Erie Dredged Material: A Preliminary Analysis, Kaylyn A. S. Flanigan, Madelyn I. Czuba, Victoria R. Riesgo, Megan A. Rúa, Louise M. Stevenson, Jari Willing

Biological Sciences Faculty Publications

While corn is considered to be a healthy food option, common agricultural practices, such as the application of soil amendments, might be introducing contaminants of concern (COC) into corn plants. The use of dredged material, which contain contaminants such as heavy metals, polychlorinated biphenyls (PCBs) and polycyclic aromatic hydrocarbons (PAHs), as a soil amendment is increasing. Contaminants from these amendments can accumulate in corn kernels harvested from plants grown on these sediments and potentially biomagnify in organisms that consume them. The extent to which secondary exposure to such contaminants in corn affect the mammalian central nervous system has been virtually …

The Impact Of Study Strategies On Knowledge Growth And Summative Exam Performance In The First Year Of Medical School, Markia Black, William L. Romine, Molly Simonis, Jeffrey L. Peters, Volker Bahn, Amber Todd

Biological Sciences Faculty Publications

Although the distinction between deep and surface processing strategies, their potential to differentially impact learning, and data supporting the superiority of deep processing strategies on summative exam scores are well supported by the literature, more work is needed to understand: (1) how medical students combine study strategies into learning practices, and (2) the effectiveness of these learning practices in facilitating knowledge gains as measured by standardized test scores.

Linking Science And Literacy Through Multimodal Text Sets: Student Perspectives, Heba Abdelnaby, William L. Romine, Delinda Van Garderen, Tracey Milarsky, Ankita Agarwal, Qingli Lei, Cassandra Smith, Amy Lannin, William Folk, Rachel Juergensen

Biological Sciences Faculty Publications

We present findings of a mixed methods study examining the perceptions of students’ (with and without disabilities) understanding and engagement with multimodal STEM text sets. Exit slip and survey data were used to identify areas for improvement in the development of the multimodal STEM text sets for middle school students. Data were collected from 434 middle school students, 86 of whom had a disability, from six teachers’ classrooms in Spring 2021. Significant differences in perceptions of understanding of argumentation were reported between students with and without disabilities. However, ratings of the lessons and the quality of learning, as well as …

Measuring Claim-Evidence-Reasoning Using Scenario-Based Assessments Grounded In Real-World Issues, William L. Romine, Amy Lannin, Ankita Agarwal, Maha Kareem, Emily Burwell

Biological Sciences Faculty Publications

Improving students’ use of argumentation is front and center in the increasing emphasis on scientific practice in K-12 Science and STEM programs. We explore the construct validity of scenario-based assessments of claim-evidence-reasoning (CER) and the structure of the CER construct with respect to a learning progression framework. We also seek to understand how middle school students progress. Establishing the purpose of an argument is a competency that a majority of middle school students meet, whereas quantitative reasoning is the most difficult, and the Rasch model indicates that the competencies form a unidimensional hierarchy of skills. We also find no evidence …

Dredged Sediments Contain Potentially Beneficial Microorganisms For Agriculture And Little Harmful Cyanobacteria, Megan A. Rúa, Ashley N. Julian, Louise Stevenson

Biological Sciences Faculty Publications

Abstract Introduction Soils worldwide are degrading, raising concerns about our ability to feed the growing global population. Soil amendments that can alleviate degradation are gaining attention. The application of sediments dredged from waterways to agricultural fields has increasing promise as a means for improving degraded soils. However, herbaceous plant species may have difficulty establishing on dredged material because of low nutrient availability, inhibitory levels of toxins, unsuitable moisture conditions and lack of microorganisms capable of ameliorating these characteristics. To counteract these issues, we sought to understand if the use of a cover crop would increase the abundance, diversity and function …

Getting To The Root Of Tree Soil Microbiome Sampling, Sarah Addison, Megan A. Rua, Simeon Smaill, Kaitlyn Daley, Brajesh Singh, Steve Wakelin

Biological Sciences Faculty Publications

Microbiomes play critical roles in host functioning and therefore there is increasing interest in the microbiome assembly of plants. However, sampling strategies for long-lived perennial trees need to be standardised to produce robust data that accurately represents the microbiome over time. This issue is currently unresolved because there is little evidence indicating which portion of perennial tree species (e.g., root region or surrounding soil) is the best to sample to produce the most accurate measure of microbiome communities. Our aim was to sample different compartments of a plant’s belowground microbiome to identify the optimal sampling strategy to account for the …

Modeling And Analysis Of The Intrinsic Cardiac Nervous System In Closed-Loop Cardiovascular Control, Michelle M. Gee, Abraham M. Lenhoff, James S. Schwaber, Babatunde A. Ogunnaike, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

The baroreceptor reflex is a multi-input, multi-output physiological control system that regulates short-term blood pressure by modulating nerve activity between the brainstem and the heart. The computational model by Park et al. (2020) is the most recent iteration in our exploration of the system. However, the contributions of”the little brain of the heart”, the intrinsic cardiac nervous system (ICN), to local control of the heart and to the integration of sensory information is unknown and has been overlooked in previous models. We have incorporated a high-fidelity representation of the ICN into a model of the baroreceptor reflex based on anatomical, …

Long-Term Exposure To An Invasive Fungal Pathogen Decreases Eptesicus Fuscus Body Mass With Increasing Latitude, Molly C. Simonis, Lynn K. Hartzler, Gregory G. Turner, Michael R. Scafini, Joseph S. Johnson, Megan A. Rúa

Biological Sciences Faculty Publications

Abstract Invasive pathogens threaten wildlife health and biodiversity. Physiological responses of species highly susceptible to pathogen infections following invasion are well described. However, the responses of less susceptible species (relative to highly susceptible species) are not well known. Latitudinal gradients, which can influence body condition via Bergmann's rule and/or reflect the time it takes for an introduced pathogen to spread geographically, add an additional layer for how mammalian species respond to pathogen exposure. Our goal was to understand how hosts less susceptible to pathogen infections respond to long‐term pathogen exposure across a broad latitudinal gradient. We examined changes in body …