Digital Commons Network^™

Graph-Regularized Dual Lasso For Robust Eqtl Mapping, Wei Cheng, Xiang Zhang, Zhishan Guo, Yu Shi, Wei Wang

Computer Science Faculty Research & Creative Works

Motivation: As a promising tool for dissecting the genetic basis of complex traits, expression quantitative trait loci (eQTL) mapping has attracted increasing research interest. An important issue in eQTL mapping is how to effectively integrate networks representing interactions among genetic markers and genes. Recently, several Lasso-based methods have been proposed to leverage such network information. Despite their success, existing methods have three common limitations: (i) a preprocessing step is usually needed to cluster the networks; (ii) the incompleteness of the networks and the noise in them are not considered; (iii) other available information, such as location of genetic markers and …

Overexpression Of Dcf1 Inhibits Glioma Through Destruction Of Mitochondria And Activation Of Apoptosis Pathway, Yuqiong Xie, Qang Li, Qingbo Yang

Electrical and Computer Engineering Faculty Research & Creative Works

Gliomas are the most common brain tumors affecting the central nervous system and are associated with a high mortality rate. DCF1 is a membrane protein that was previously found to play a role in neural stem cell differentiation. In the present study, we found that overexpression of dcf1 significantly inhibited cell proliferation, migration, and invasion and dramatically promoted apoptosis in the glioblastoma U251 cell line. DCF1 deletion mutations in the functional region showed that the complete structure of DCF1 was necessary for apoptosis. Furthermore, significantly lower tumorigenicity was observed in athymic nude mice by transplanting U251 cells overexpressing dcf1. To …

Oxidative Stress Disruption Of Receptor-Mediated Calcium Signaling Mechanisms, Tso-Hao Tang, Chiung-Tan Chang, Hsiu-Jen Wang, Joshua Erickson, Rhett A. Reichard, Alexis Martin, Erica Shannon, Adam L. Martin, Yue-Wern Huang, Robert Aronstam

Biological Sciences Faculty Research & Creative Works

Background: Oxidative stress increases the cytosolic content of calcium in the cytoplasm through a combination of effects on calcium pumps, exchangers, channels and binding proteins. In this study, oxidative stress was produced by exposure to tert-butyl hydroperoxide (tBHP); cell viability was assessed using a dye reduction assay; receptor binding was characterized using [³H]N-methylscopolamine ([³H]MS); and cytosolic and luminal endoplasmic reticulum (ER) calcium concentrations ([Ca²⁺]_i and [Ca²⁺]_L, respectively) were measured by fluorescent imaging.

Results: Activation of M3 muscarinic receptors induced a biphasic increase in [Ca²⁺] …

Molecular Diversity Of Bacteroidales In Fecal And Environmental Samples And Swine-Associated Subpopulations, Regina Lamendella, Kent C. Li, Daniel B. Oerther, Jorge W. Santo Domingo

Civil, Architectural and Environmental Engineering Faculty Research & Creative Works

Several swine-specific microbial source tracking methods are based on PCR assays targeting Bacteroidales 16S rRNA gene sequences. The limited application of these assays can be explained by the poor understanding of their molecular diversity in fecal sources and environmental waters. In order to address this, we studied the diversity of 9,340 partial (>600bp in length) Bacteroidales 16S rRNA gene sequences from 13 fecal sources and nine feces-contaminated watersheds. The compositions of major Bacteroidales populations were analyzed to determine which host and environmental sequences were contributing to each group. This information allowed us to identify populations which were both exclusive …

Rna Profiles Of Porcine Embryos During Genome Activation Reveal Complex Metabolic Switch Sensitive To In Vitro Conditions, Olga Østrup, Gayla R. Olbricht, Esben Østrup, Poul Hyttel, Philippe Collas, Ryan A. Cabot

Mathematics and Statistics Faculty Research & Creative Works

Fertilization is followed by complex changes in cytoplasmic composition and extensive chromatin reprogramming which results in the abundant activation of totipotent embryonic genome at embryonic genome activation (EGA). While chromatin reprogramming has been widely studied in several species, only a handful of reports characterize changing transcriptome profiles and resulting metabolic changes in cleavage stage embryos. The aims of the current study were to investigate RNA profiles of in vivo developed (ivv) and in vitro produced (ivt) porcine embryos before (2-cell stage) and after (late 4-cell stage) EGA and determine major metabolic changes that regulate totipotency. The period before EGA was …

Comparative Fecal Metagenomics Unveils Unique Functional Capacity Of The Swine Gut, Regina Lamendella, Jorge W. Santo Domingo, Shreya Ghosh, John Martinson, Daniel B. Oerther

Civil, Architectural and Environmental Engineering Faculty Research & Creative Works

Background: Uncovering the taxonomic composition and functional capacity within the swine gut microbial consortia is of great importance to animal physiology and health as well as to food and water safety due to the presence of human pathogens in pig feces. Nonetheless, limited information on the functional diversity of the swine gut microbiome is available. Results: Analysis of 637, 722 pyrosequencing reads (130 megabases) generated from Yorkshire pig fecal DNA extracts was performed to help better understand the microbial diversity and largely unknown functional capacity of the swine gut microbiome. Swine fecal metagenomic sequences were annotated using both MG-RAST and …

Nona-Arginine Facilitates Delivery Of Quantum Dots Into Cells Via Multiple Pathways, Yi Xu, Betty Revon Liu, Han Jung Lee, Katie Shannon, Jeffrey G. Winiarz, Tien-Chun Wang, Huey-Jenn Chiang, Yue-Wern Huang

Biological Sciences Faculty Research & Creative Works

Semiconductor quantum dots (QDs) have recently been used to deliver and monitor biomolecules, such as drugs and proteins. However, QDs alone have a low efficiency of transport across the plasma membrane. In order to increase the efficiency, we used synthetic nona-arginine (SR9), a cell-penetrating peptide, to facilitate uptake. We found that SR9 increased the cellular uptake of QDs in a noncovalent binding manner between QDs and SR9. Further, we investigated mechanisms of QD/SR9 cellular internalization. Low temperature and metabolic inhibitors markedly inhibited the uptake of QD/SR9, indicating that internalization is an energy-dependent process. Results from both the pathway inhibitors and …

A Framework For Automated Enrichment Of Functionally Significant Inverted Repeats In Whole Genomes, Cyriac Kandoth, Fikret ErçAl, Ronald L. Frank

Computer Science Faculty Research & Creative Works

Background: RNA transcripts from genomic sequences showing dyad symmetry typically adopt hairpin-like, cloverleaf, or similar structures that act as recognition sites for proteins. Such structures often are the precursors of non-coding RNA (ncRNA) sequences like microRNA (miRNA) and small-interfering RNA (siRNA) that have recently garnered more functional significance than in the past. Genomic DNA contains hundreds of thousands of such inverted repeats (IRs) with varying degrees of symmetry. But by collecting statistically significant information from a known set of ncRNA, we can sort these IRs into those that are likely to be functional.

Results: A novel method was developed to …

Bub2 Regulation Of Cytokinesis And Septation In Budding Yeast, Su Young Park, Addie E. Cable, Jessica Blair, Katherine E. Stockstill, Katie Shannon

Biological Sciences Faculty Research & Creative Works

Background: The mitotic exit network (MEN) is required for events at the end of mitosis such as degradation of mitotic cyclins and cytokinesis. Bub2 and its binding partner Bfa1 act as a GTPase activating protein (GAP) to negatively regulate the MEN GTPase Tem1. The Bub2/Bfa1 checkpoint pathway is required to delay the cell cycle in response to mispositioned spindles. In addition to its role in mitotic exit, Tem1 is required for actomyosin ring contraction.

Results: To test the hypothesis that the Bub2 pathway prevents premature actin ring assembly, we compared the timing of actin ring formation in wild type, bub2Δ …

Clustering Of High-Dimensional Gene Expression Data With Feature Filtering Methods And Diffusion Maps, Rui Xu, Steven Damelin, Boaz Nadler, Donald C. Wunsch

Electrical and Computer Engineering Faculty Research & Creative Works

The importance of gene expression data in cancer diagnosis and treatment by now has been widely recognized by cancer researchers in recent years. However, one of the major challenges in the computational analysis of such data is the curse of dimensionality, due to the overwhelming number of measures of gene expression levels versus the small number of samples. Here, we use a two-step method to reduce the dimension of gene expression data. At first, we extract a subset of genes based on the statistical characteristics of their corresponding gene expression measurements. For further dimensionality reduction, we then apply diffusion maps, …

Applications Of Diffusion Maps In Gene Expression Data-Based Cancer Diagnosis Analysis, Rui Xu, Donald C. Wunsch, Steven Damelin

Electrical and Computer Engineering Faculty Research & Creative Works

Early detection of a tumor's site of origin is particularly important for cancer diagnosis and treatment. The employment of gene expression profiles for different cancer types or subtypes has already shown significant advantages over traditional cancer classification methods. One of the major problems in cancer type recognition-oriented gene expression data analysis is the overwhelming number of measures of gene expression levels versus the small number of samples, which causes the curse of dimension issue. Here, we use diffusion maps, which interpret the eigenfunctions of Markov matrices as a system of coordinates on the original data set in order to obtain …

Gene Expression Data For Dlbcl Cancer Survival Prediction With A Combination Of Machine Learning Technologies, Rui Xu, Xindi Cai, Donald C. Wunsch

Electrical and Computer Engineering Faculty Research & Creative Works

Gene expression profiles have become an important and promising way for cancer prognosis and treatment. In addition to their application in cancer class prediction and discovery, gene expression data can be used for the prediction of patient survival. Here, we use particle swarm optimization (PSO) to address one of the major challenges in gene expression data analysis, the curse of dimensionality, in order to discriminate high risk patients from low risk patients. A discrete binary version of PSO is used for gene selection and dimensionality reduction, and a probabilistic neural network (PNN) is implemented as the classifier. The experimental results …

Gene Regulatory Networks Inference With Recurrent Neural Network Models, Rui Xu, Donald C. Wunsch

Electrical and Computer Engineering Faculty Research & Creative Works

Large-scale time series gene expression data generated from DNA microarray experiments provide us a new means to reveal fundamental cellular processes, investigate functions of genes, and understand their relations and interactions. To infer gene regulatory networks from these data with effective computational tools has attracted intensive efforts from artificial intelligence and machine learning. Here, we use a recurrent neural network (RNN), trained with particle swarm optimization (PSO), to investigate the behaviors of regulatory networks. The experimental results, on a synthetic data set and a real data set, show that the proposed model and algorithm can effectively capture the dynamics of …

Multi-Class Cancer Classification By Semi-Supervised Ellipsoid Artmap With Gene Expression Data, Rui Xu, Donald C. Wunsch, Georgios C. Anagnostopoulos

Electrical and Computer Engineering Faculty Research & Creative Works

To accurately identify the site of origin of a tumor is crucial to cancer diagnosis and treatment. With the emergence of DNA microarray technologies, constructing gene expression profiles for different cancer types has already become a promising means for cancer classification. In addition to binary classification, the discrimination of multiple tumor types is also important semi-supervised ellipsoid ARTMAP (ssEAM) is a novel neural network architecture rooted in adaptive resonance theory suitable for classification tasks. ssEAM can achieve fast, stable and finite learning and create hyper-ellipsoidal clusters inducing complex nonlinear decision boundaries. Here, we demonstrate the capability of ssEAM to discriminate …

Inference Of Genetic Regulatory Networks With Recurrent Neural Network Models, Rui Xu, Xiao Hu, Donald C. Wunsch

Electrical and Computer Engineering Faculty Research & Creative Works

Large-scale gene expression data coming from microarray experiments provide us a new means to reveal fundamental cellular processes, investigate functions of genes, and understand relations and interactions among them. To infer genetic regulatory networks from these data with effective computational tools has become increasingly important Several mathematical models, including Boolean networks, Bayesian networks, dynamic Bayesian networks, and linear additive regulation models, have been used to explore the behaviors of regulatory networks. In this paper, we investigate the inference of genetic regulatory networks from time series gene expression in the framework of recurrent neural network model.

Mad2 And Bubr1 Function In A Single Checkpoint Pathway That Responds To A Loss Of Tension, Katie Shannon, Julie C. Canman, Edward D. Salmon

Biological Sciences Faculty Research & Creative Works

The spindle checkpoint monitors microtubule attachment and tension at kinetochores to ensure proper chromosome segregation. Previously, PtK1 cells in hypothermic conditions (23°C) were shown to have a pronounced mitotic delay, despite having normal numbers of kinetochore microtubules. At 23°C, we found that PtK1 cells remained in metaphase for an average of 101 min, compared with 21 min for cells at 37°C. The metaphase delay at 23°C was abrogated by injection of Mad2 inhibitors, showing that Mad2 and the spindle checkpoint were responsible for the prolonged metaphase. Live cell imaging showed that kinetochore Mad2 became undetectable soon after chromosome congression. Measurements …

Abnormal Cell Detection Using The Choquet Integral, R. Joe Stanley, James M. Keller, Charles William Caldwell, Paul D. Gader

Electrical and Computer Engineering Faculty Research & Creative Works

Automated Giemsa-banded chromosome image research has been largely restricted to classification schemes associated with isolated chromosomes within metaphase spreads. In normal human metaphase spreads, there are 46 chromosomes occurring in homologous pairs for the autosomal classes 1-22 and the X chromosome for females. Many genetic abnormalities are directly linked to structural and/or numerical aberrations of chromosomes within metaphase spreads. Cells with the Philadelphia chromosome contain an abnormal chromosome for class 9 and for class 22, leaving a single normal chromosome for each class. A data-driven homologue matching technique is applied to recognizing normal chromosomes from classes 9 and 22. Homologue …

Data-Driven Homologue Matching For Chromosome Identification, R. Joe Stanley, James M. Keller, Paul D. Gader, Charles William Caldwell

Electrical and Computer Engineering Faculty Research & Creative Works

Karyotyping involves the visualization and classification of chromosomes into standard classes. In "normal" human metaphase spreads, chromosomes occur in homologous pairs for the autosomal classes 1-22, and X chromosome for females. Many existing approaches for performing automated human chromosome image analysis presuppose cell normalcy, containing 46 chromosomes within a metaphase spread with two chromosomes per class. This is an acceptable assumption for routine automated chromosome image analysis. However, many genetic abnormalities are directly linked to structural or numerical aberrations of chromosomes within the metaphase spread. Thus, two chromosomes per class cannot be assumed for anomaly analysis. This paper presents the …