Domainrbf: A Bayesian Regression Approach To The Prioritization Of Candidate Domains For Complex Diseases., Wangshu Zhang, Yong Chen, Fengzhu Sun, Rui Jiang
BACKGROUND: Domains are basic units of proteins, and thus exploring associations between protein domains and human inherited diseases will greatly improve our understanding of the pathogenesis of human complex diseases and further benefit the medical prevention, diagnosis and treatment of these diseases. Within a given domain-domain interaction network, we make the assumption that similarities of disease phenotypes can be explained using proximities of domains associated with such diseases. Based on this assumption, we propose a Bayesian regression approach named "domainRBF" (domain Rank with Bayes Factor) to prioritize candidate domains for human complex diseases.
RESULTS: Using a compiled dataset containing 1 ...
Creating A Molecular Map Of The Pediatric Lung, 2019 College of Saint Benedict/Saint John's University
Creating A Molecular Map Of The Pediatric Lung, Quinlen F. Marshall
The newborn lung undergoes vast biochemical and physiological changes during adaptation from the intrauterine to the extrauterine environment. Lung morphogenesis continues from birth into early childhood, mediated by dynamic gene expression and a diversity of pulmonary cell types that exhibit remarkable heterogeneity. (Whitsett, JA. et al. Physiol. Rev, 2019). Surprisingly, few studies have solely focused on human lung development during this critical period, and many current studies of lung maturation rely on adult, murine, or diseased samples, limiting their insights and applicability to longitudinal pediatric lung development. Understanding the molecular and physiological nuances of pulmonary development has important clinical relevance ...
Mouth Function Determines The Shape Oscillation Pattern In Regenerating Hydra Tissue Spheres, 2019 Swarthmore College
Mouth Function Determines The Shape Oscillation Pattern In Regenerating Hydra Tissue Spheres, R. Wang, T. Goel, K. Khazoyan, Ziad Sabry , '21, H. J. Quan, P. H. Diamond, Eva-Maria S. Collins
Biology Faculty Works
Hydra is a small freshwater polyp capable of regeneration from small tissue pieces and from aggregates of cells. During regeneration, a hollow bilayered sphere is formed that undergoes osmotically driven shape oscillations of inflation and rupture. These oscillations are necessary for successful regeneration. Eventually, the oscillating sphere breaks rotational symmetry along the future head-foot axis of the animal. Notably, the shape oscillations show an abrupt shift from large-amplitude, long-period oscillations to small-amplitude, short-period oscillations. It has been widely accepted that this shift in oscillation pattern is linked to symmetry breaking and axis formation, and current theoretical models of Hydra symmetry ...
Modeling Of Cisplatin-Induced Signaling Dynamics In Triple-Negative Breast Cancer Cells Reveals Mediators Of Sensitivity, 2019 University of Groningen
Modeling Of Cisplatin-Induced Signaling Dynamics In Triple-Negative Breast Cancer Cells Reveals Mediators Of Sensitivity, Anne Margriet Heijink, Marieke Everts, Megan E. Honeywell, Ryan Richards, Yannick P. Kok, Elisabeth G. E. De Vries, Michael J. Lee, Marcel A T M Van Vugt
Open Access Articles
Triple-negative breast cancers (TNBCs) display great diversity in cisplatin sensitivity that cannot be explained solely by cancer-associated DNA repair defects. Differential activation of the DNA damage response (DDR) to cisplatin has been proposed to underlie the observed differential sensitivity, but it has not been investigated systematically. Systems-level analysis-using quantitative time-resolved signaling data and phenotypic responses, in combination with mathematical modeling-identifies that the activation status of cell-cycle checkpoints determines cisplatin sensitivity in TNBC cell lines. Specifically, inactivation of the cell-cycle checkpoint regulator MK2 or G3BP2 sensitizes cisplatin-resistant TNBC cell lines to cisplatin. Dynamic signaling data of five cell cycle-related signals predicts ...
Phylogenetic Trees And Networks Can Serve As Powerful And Complementary Approaches For Analysis Of Genomic Data, 2019 CUNY New York City College of Technology
Phylogenetic Trees And Networks Can Serve As Powerful And Complementary Approaches For Analysis Of Genomic Data, Christopher Blair, Cécile Ané
Publications and Research
Genomic data have had a profound impact on nearly every biological discipline. In systematics and phylogenetics, the thousands of loci that are now being sequenced can be analyzed under the multispecies coalescent model (MSC) to explicitly account for gene tree discordance due to incomplete lineage sorting (ILS). However, the MSC assumes no gene flow post divergence, calling for additional methods that can accommodate this limitation. Explicit phylogenetic network methods have emerged, which can simultaneously account for ILS and gene flow by representing evolutionary history as a directed acyclic graph. In this point-of-view we highlight some of the strengths and limitations ...
Temporal Gene Expression Of Mesenchymal Cells In The Pediatric Lung, 2019 College of Saint Benedict/Saint John's University
Temporal Gene Expression Of Mesenchymal Cells In The Pediatric Lung, Quinlen F. Marshall, Soumyaroop Bhattacharya, Gautam Bandyopadhyay, Ravi Misra, Thomas Mariani, Gloria Pryhuber
Chemistry Student Work
INTRODUCTION: The newborn lung undergoes vast biochemical and physiological changes during adaptation from the intrauterine to the extrauterine environment. Lung morphogenesis continues from birth into early childhood, mediated by dynamic gene expression and a diversity of pulmonary cell types (Whitsett, JA. et al. Physiol. Rev, 2019). Murine models demonstrate that pulmonary mesenchymal cells exhibit remarkable heterogeneity in function and morphology during development, however, confirmation of their role is lacking in human neonates and early childhood (Guo, M. et al. Nat. Comm, 2019). In addition, many current human genomic studies of lung maturation suffer from limited sample size, limiting their applicability ...
The Mayfly Newsletter, 2019 The Permanent Committee of the International Conferences on Ephemeroptera
The Mayfly Newsletter, Donna J. Giberson
The Mayfly Newsletter
The Mayfly Newsletter is the official newsletter of the Permanent Committee of the International Conferences on Ephemeroptera.
High-Fat Diet In A Mouse Insulin-Resistant Model Induces Widespread Rewiring Of The Phosphotyrosine Signaling Network, 2019 Massachusetts Institute of Technology
High-Fat Diet In A Mouse Insulin-Resistant Model Induces Widespread Rewiring Of The Phosphotyrosine Signaling Network, Antje Dittmann, Norman J. Kennedy, Nina L. Soltero, Nader Morshed, Miyeko D. Mana, Omer H. Yilmaz, Roger J. Davis, Forest M. White
Open Access Articles
Obesity-associated type 2 diabetes and accompanying diseases have developed into a leading human health risk across industrialized and developing countries. The complex molecular underpinnings of how lipid overload and lipid metabolites lead to the deregulation of metabolic processes are incompletely understood. We assessed hepatic post-translational alterations in response to treatment of cells with saturated and unsaturated free fatty acids and the consumption of a high-fat diet by mice. These data revealed widespread tyrosine phosphorylation changes affecting a large number of enzymes involved in metabolic processes as well as canonical receptor-mediated signal transduction networks. Targeting two of the most prominently affected ...
Systems Approach Reveals Photosensitivity And Per2 Level As Determinants Of Clock-Modulator Efficacy, 2019 Korea Advanced Institute of Science and Technology
Systems Approach Reveals Photosensitivity And Per2 Level As Determinants Of Clock-Modulator Efficacy, Dae Wook Kim, Cheng Chang, Xian Chen, Angela C. Doran, Francois Gaudreault, Travis Wager, George J. Demarco, Jae Kyoung Kim
Open Access Articles
In mammals, the master circadian clock synchronizes daily rhythms of physiology and behavior with the day-night cycle. Failure of synchrony, which increases the risk for numerous chronic diseases, can be treated by phase adjustment of the circadian clock pharmacologically, for example, with melatonin, or a CK1delta/epsilon inhibitor. Here, using in silico experiments with a systems pharmacology model describing molecular interactions, and pharmacokinetic and behavioral experiments in cynomolgus monkeys, we find that the circadian phase delay caused by CK1delta/epsilon inhibition is more strongly attenuated by light in diurnal monkeys and humans than in nocturnal mice, which are common preclinical ...
Novel Strategies On Characterizing Biologically Specific Protein-Protein Interaction Networks, 2019 University of South Florida
Novel Strategies On Characterizing Biologically Specific Protein-Protein Interaction Networks, Bi Zhao
Graduate Theses and Dissertations
The function, behavior, and environmental response of biological systems are essentially determined by the complex interaction and regulation of biomolecules inside the systems. Therefore, it is critical to characterize the inter-molecular interaction and regulation of biomolecules inside these systems. In this direction, many experimental techniques have been developed and these techniques have been used in many different model systems under various conditions. Consequently, a massive amount of data has been generated. These data cover multiple aspects of molecular interaction and regulation, such as protein-protein interaction, microRNA-RNA interaction, gene expression profiles, etc. While carrying rich information, these data may also contain ...
Structure-Based Design Of Hepatitis C Virus Vaccines That Elicit Neutralizing Antibody Responses To A Conserved Epitope, 2019 University of Massachusetts Medical School
Structure-Based Design Of Hepatitis C Virus Vaccines That Elicit Neutralizing Antibody Responses To A Conserved Epitope, Brian G. Pierce, Elisabeth N. Boucher, Kurt H. Piepenbrink, Ejemel Monir, Chelsea A. Rapp, William D. Thomas Jr., Eric J. Sundberg, Zhiping Weng, Yan Wang
Despite recent advances in therapeutic options, hepatitis C virus (HCV) remains a severe global disease burden, and a vaccine can substantially reduce its incidence. Due to its extremely high sequence variability, HCV can readily escape the immune response; thus, an effective vaccine must target conserved, functionally important epitopes. Using the structure of a broadly neutralizing antibody in complex with a conserved linear epitope from the HCV E2 envelope glycoprotein (residues 412 to 423; epitope I), we performed structure-based design of immunogens to induce antibody responses to this epitope. This resulted in epitope-based immunogens based on a cyclic defensin protein, as ...
Do Metabolic Networks Follow A Power Law? A Psamm Analysis, 2019 University of Rhode Island
Do Metabolic Networks Follow A Power Law? A Psamm Analysis, Ryan Geib, Lubos Thoma, Ying Zhang
Senior Honors Projects
Inspired by the landmark paper “Emergence of Scaling in Random Networks” by Barabási and Albert, the field of network science has focused heavily on the power law distribution in recent years. This distribution has been used to model everything from the popularity of sites on the World Wide Web to the number of citations received on a scientific paper. The feature of this distribution is highlighted by the fact that many nodes (websites or papers) have few connections (internet links or citations) while few “hubs” are connected to many nodes. These properties lead to two very important observed effects: the ...
The Use Of Foundational Mathematical Modeling Techniques To Inform Understanding & Design Of Complex Biological Systems, Callan Monette
Undergraduate Honors Theses
Synthetic biology is a relatively new and diverse field with the potential to revolutionize our command over biological systems via the modification or de novo construction of biological networks and tools. Precise and predictable control over the foundational properties of gene expression and genetic circuit behavior will be critical to the application of synthetic biology in the relevant contexts (for instance, in vivo for therapeutic applications). This level of control can be achieved via the interplay between mathematical modeling and empirical observation. The following work will highlight not only the massive potential of synthetic biology in both bacterial and mammalian ...
Screening For Neurotoxic Potential Of 15 Flame Retardants Using Freshwater Planarians, 2019 Swarthmore College
Screening For Neurotoxic Potential Of 15 Flame Retardants Using Freshwater Planarians, S. Zhang, D. Ireland, N. S. Sipes, M. Behl, Eva-Maria S. Collins
Biology Faculty Works
Asexual freshwater planarians are an attractive invertebrate model for high-throughput neurotoxicity screening, because they possess multiple quantifiable behaviors to assess distinct neuronal functions. Planarians uniquely allow direct comparisons between developing and adult animals to distinguish developmentally selective effects from general neurotoxicity. In this study, we used our automated planarian screening platform to compare the neurotoxicity of 15 flame retardants (FRs), consisting of representative phased-out brominated (BFRs) and replacement organophosphorus FRs (OPFRs). OPFRs have emerged as a proposed safer alternative to BFRs; however, limited information is available on their health effects. We found 11 of the 15 FRs (3/6 BFRs ...
Co2 Flux And C Balance Due To The Replacement Of Bare Soil With Agro-Ecological Service Crops In Mediterranean Environment, Emanuele Radicetti, O. Adewale Osipitan, Ali Reza Safahani Langeroodi, Sara Marinari, Roberto Mancinelli
Haskell Agricultural Laboratory (Northeast Research and Extension Center)
Intensive agriculture practices often results in decomposition of organic matter, thus causing soil CO2 emissions. Agro-ecological service crop could be profitably cultivated to improve soil characteristics and reduce CO2 emissions under Mediterranean environment. Two-year field trials were conducted in central Italy. The treatments were three agro-ecological service crops (hairy vetch, oat, and oilseed rape) and a no-service cover. Plant development, soil characteristics, and CO2 emissions were measured. Oat and oilseed rape showed a rapid growth, while hairy vetch started to grow rapidly only after the cold period. Soil CO2 emissions trend was similar among the agro-ecological ...
Camera Trap Study Of The Mammal Communities Across An Urbanization Gradient, 2019 Pittsburg State University
Camera Trap Study Of The Mammal Communities Across An Urbanization Gradient, Caleb Durbin, Christine Brodsky
Urbanization impacts mammal communities due to habitat removal, resource abundance distribution, and the introduction of exotic species. Other studies have found that wildlife species richness is greatest at intermediate urbanization, while abundance is greatest in cities. This study was done to explore the mammal community across an urban to rural gradient in Pittsburg. Using motion-sensor camera traps, we documented small mammal presence for 24 hours a day, finding patterns in mammal abundance, species richness, and community composition. Our hypothesis was that we will observe trends in mammal communities similar to other cities. Over six weeks, we placed two cameras ...
Functional Feeding Groups Of Aquatic Macroinvertebrates On Natural And Artificial Leaves In Forested Stream Habitats In The Sebago Lake Land Reserve, Sam H. Matey, Kala Freytag Wistar
Thinking Matters Symposium Archive
We investigated preferential insect colonization of natural versus artificial leaves in forested streams to determine the impact of invertebrate-substrate associations on macroinvertebrate community composition and ecosystem nutrient cycling. We created 10 onion bags filled with natural maple leaves and 10 filled with artificial maple leaves, and placed 5 of each in two forested streams, one larger and one smaller, in the Sebago Lake Land Reserve in Standish, Maine. We identified the aquatic macroinvertebrates found on these samples after approximately one month to order-level and used Maine DEP biomonitoring data and functional feeding group taxonomies to classify macroinvertebrates by functional feeding ...
Measuring The Reproducibility And Quality Of Hi-C Data, 2019 University of Washington
Measuring The Reproducibility And Quality Of Hi-C Data, Galip Gurkan Yardimci, Hakan Ozadam, Bryan R. Lajoie, Ye Zhan, Job Dekker, William S. Noble
Open Access Articles
BACKGROUND: Hi-C is currently the most widely used assay to investigate the 3D organization of the genome and to study its role in gene regulation, DNA replication, and disease. However, Hi-C experiments are costly to perform and involve multiple complex experimental steps; thus, accurate methods for measuring the quality and reproducibility of Hi-C data are essential to determine whether the output should be used further in a study.
RESULTS: Using real and simulated data, we profile the performance of several recently proposed methods for assessing reproducibility of population Hi-C data, including HiCRep, GenomeDISCO, HiC-Spector, and QuASAR-Rep. By explicitly controlling noise ...
Genome-Wide Prediction Of Synthetic Rescue Mediators Of Resistance To Targeted And Immunotherapy, 2019 Harvard Medical School
Genome-Wide Prediction Of Synthetic Rescue Mediators Of Resistance To Targeted And Immunotherapy, Avinash Das Sahu, Olga Ponomarova, Eytan Ruppin
Open Access Articles
Most patients with advanced cancer eventually acquire resistance to targeted therapies, spurring extensive efforts to identify molecular events mediating therapy resistance. Many of these events involve synthetic rescue (SR) interactions, where the reduction in cancer cell viability caused by targeted gene inactivation is rescued by an adaptive alteration of another gene (the rescuer). Here, we perform a genome-wide in silico prediction of SR rescuer genes by analyzing tumor transcriptomics and survival data of 10,000 TCGA cancer patients. Predicted SR interactions are validated in new experimental screens. We show that SR interactions can successfully predict cancer patients' response and emerging ...
Student-Faculty Collaborative Research Grant Report, 2019 Linfield College
Student-Faculty Collaborative Research Grant Report, Megan Bestwick
Mitochondria are essential organelles in most eukaryotic cells because of their role in metabolism and the production of ATP by the oxidative phosphorylation (OXPHOS) pathway, as well as other key cellular processes. Metal cofactors, such as copper (Cu) and iron (Fe), are incorporated into OXPHOS protein complexes of yeast located within the inner membrane of the mitochondria. Misincorporation or modulation of these available metals in mitochondrial enzymes leads to the production of reactive oxygen species (ROS). ROS are reactive molecules containing oxygen such as peroxides, superoxide, and hydroxyl radicals. Yeast are a good model for studying aging and the effect ...