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Search Results: 1 - 10 of 126934 matches for " William O Ward "
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Discovering collectively informative descriptors from high-throughput experiments
Clark D Jeffries, William O Ward, Diana O Perkins, Fred A Wright
BMC Bioinformatics , 2009, DOI: 10.1186/1471-2105-10-431
Abstract: This paper describes a novel algorithm called BLANKET for symmetric analysis of two experiments that assess informativeness of descriptors. The experiments are required to be related only in that their descriptor sets intersect substantially and their definitions of case and control are consistent. From resulting lists of n descriptors ranked by informativeness, BLANKET determines shortlists of descriptors from each experiment, generally of different lengths p and q. For any pair of shortlists, four numbers are evident: the number of descriptors appearing in both shortlists, in exactly one shortlist, or in neither shortlist. From the associated contingency table, BLANKET computes Right Fisher Exact Test (RFET) values used as scores over a plane of possible pairs of shortlist lengths [1,2]. BLANKET then chooses a pair or pairs with RFET score less than a threshold; the threshold depends upon n and shortlist length limits and represents a quality of intersection achieved by less than 5% of random lists.Researchers seek within a universe of descriptors some minimal subset that collectively and efficiently predicts experimental outcomes. Ideally, any smaller subset should be insufficient for reliable prediction and any larger subset should have little additional accuracy. As a method, BLANKET is easy to conceptualize and presents only moderate computational complexity. Many existing databases could be mined using BLANKET to suggest optimal sets of predictive descriptors.In contemporary high-throughput experiments, very many descriptor values can be measured, leading to the issue of correction for multiple testing to minimize false positives at the cost of a high number of false negatives. Reconciliation entails compromises that are to some extent arbitrary. A deterministic method is needed for selecting a minimal, distinguished set of descriptors that collectively provide effective, efficient prediction. Researchers can subsequently investigate members of such a subset
Kidney Toxicogenomics of Chronic Potassium Bromate Exposure in F344 Male Rats
David R. Geter,William O. Ward,Geremy W. Knapp,Anthony B. DeAngelo
Translational Oncogenomics , 2006,
Abstract: Background: Potassium bromate (KBrO3), used in both the food and cosmetics industry, and a drinking water disinfection by-product, is a nephrotoxic compound and rodent carcinogen. To gain insight into the carcinogenic mechanism of action and provide possible biomarkers of KBrO3 exposure, the gene expression in kidneys from chronically exposed male F344 rats was investigated.Methods: Male F344 rats were exposed to KBrO3 in drinking water for 52 and 100 wk. Kidneys were removed, frozen, and stored at –80oC, then used for Affymetrix microarray analysis. Gene expression patterns were examined using a non-carcinogenic (20 ppm) and carcinogenic dose (400 ppm) at 52 wk, and compared to 100 wk high dose (400 ppm) and adenoma gene expression.Results: Statistical analysis revealed 144, 224, 43, and 994 genes out of 15866 from the 52 wk low, 52 wk high, 100 wk high, and adenomas respectively, were differentially expressed when compared to control kidneys. Gene ontology classification of the 52 wk high dose showed alterations of gene transcripts involved in oxidative stress, lipid metabolism, kidney function/ion transport, and cellular function. In a comparison of kidney development gene expression, alterations were seen in the adenomas but not in the 52 wk bromate-treated kidneys. However, the normal kidney from the high dose group resembled the adenoma expression pattern with early kidney development genes being up-regulated and adult phase genes being down-regulated. Moreover, eight genes were identified which could serve as biomarkers of carcinogenic exposure to bromate. The most promising of these was Pendrin, or Slc26a4, a solute carrier of chloride and iodide active in the kidney, thyroid, and inner ear. All these tissues are targets of KBrO3 toxicity. Expression array results were verified with quantitative real-time rtPCR.Conclusions: These data demonstrate that the 400 ppm carcinogenic dose of KBrO3 showed marked gene expression differences from the 20 ppm non-carcinogenic dose. Comparison of kidney development gene expression showed that the adenoma patterns were more characteristic of embryonic than adult kidneys, and that the normal kidney from the high dose group resembled the adenoma-like gene expression pattern. Taken together, the analysis from this study identifies potential biomarkers of exposure and illuminates a possible carcinogenic mode of action for KBrO3.
Competition-induced criticality in a model of meme popularity
James P. Gleeson,Jonathan A. Ward,Kevin P. O'Sullivan,William T. Lee
Physics , 2013, DOI: 10.1103/PhysRevLett.112.048701
Abstract: Heavy-tailed distributions of meme popularity occur naturally in a model of meme diffusion on social networks. Competition between multiple memes for the limited resource of user attention is identified as the mechanism that poises the system at criticality. The popularity growth of each meme is described by a critical branching process, and asymptotic analysis predicts power-law distributions of popularity with very heavy tails (exponent $\alpha<2$, unlike preferential-attachment models), similar to those seen in empirical data.
Hepatic Xenobiotic Metabolizing Enzyme and Transporter Gene Expression through the Life Stages of the Mouse
Janice S. Lee, William O. Ward, Jie Liu, Hongzu Ren, Beena Vallanat, Don Delker, J. Christopher Corton
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0024381
Abstract: Background Differences in responses to environmental chemicals and drugs between life stages are likely due in part to differences in the expression of xenobiotic metabolizing enzymes and transporters (XMETs). No comprehensive analysis of the mRNA expression of XMETs has been carried out through life stages in any species. Results Using full-genome arrays, the mRNA expression of all XMETs and their regulatory proteins was examined during fetal (gestation day (GD) 19), neonatal (postnatal day (PND) 7), prepubescent (PND32), middle age (12 months), and old age (18 and 24 months) in the C57BL/6J (C57) mouse liver and compared to adults. Fetal and neonatal life stages exhibited dramatic differences in XMET mRNA expression compared to the relatively minor effects of old age. The total number of XMET probe sets that differed from adults was 636, 500, 84, 5, 43, and 102 for GD19, PND7, PND32, 12 months, 18 months and 24 months, respectively. At all life stages except PND32, under-expressed genes outnumbered over-expressed genes. The altered XMETs included those in all of the major metabolic and transport phases including introduction of reactive or polar groups (Phase I), conjugation (Phase II) and excretion (Phase III). In the fetus and neonate, parallel increases in expression were noted in the dioxin receptor, Nrf2 components and their regulated genes while nuclear receptors and regulated genes were generally down-regulated. Suppression of male-specific XMETs was observed at early (GD19, PND7) and to a lesser extent, later life stages (18 and 24 months). A number of female-specific XMETs exhibited a spike in expression centered at PND7. Conclusions The analysis revealed dramatic differences in the expression of the XMETs, especially in the fetus and neonate that are partially dependent on gender-dependent factors. XMET expression can be used to predict life stage-specific responses to environmental chemicals and drugs.
Toxicogenomic analysis incorporating operon-transcriptional coupling and toxicant concentration-expression response: analysis of MX-treated Salmonella
William O Ward, Carol D Swartz, Steffen Porwollik, Sarah H Warren, Nancy M Hanley, Geremy W Knapp, Michael McClelland, David M DeMarini
BMC Bioinformatics , 2007, DOI: 10.1186/1471-2105-8-378
Abstract: Operon analysis increased the number of altered genes by 95% from the list identified by a Bayesian t-test of control to the highest concentration of MX. Monotonic analysis added 46% more genes. A functional analysis of the resulting 448 differentially expressed genes yielded functional changes beyond what would be expected from only the mutagenic properties of MX. In addition to gene-expression changes in DNA-damage response, MX induced changes in expression of genes involved in membrane transport and porphyrin metabolism, among other biological processes. The disruption of porphyrin metabolism might be attributable to the structural similarity of MX, which is a chlorinated furanone, to ligands indigenous to the porphyrin metabolism pathway. Interestingly, our results indicate that the lexA regulon in Salmonella, which partially mediates the response to DNA damage, may contain only 60% of the genes present in this regulon in E. coli. In addition, nanH was found to be highly induced by MX and contains a putative lexA regulatory motif in its regulatory region, suggesting that it may be regulated by lexA.Operon and monotonic analyses improved the determination of differentially expressed genes beyond that of Bayesian-t analysis, showing that MX alters cellular metabolism involving pathways other than DNA damage. Because co-expression of similarly functioning genes also occurs in eukaryotes, this method has general applicability for improving analysis of toxicogenomic data.Deficiencies in microarray technology can produce undesired variation in the hybridization signal, obscuring a clear measurement of intracellular transcript levels. In order to overcome this problem, we applied two analytical techniques in addition to the typically used t-test to discern differentially expressed genes. We used (a) an operon analysis that assumes if one gene in an operon is differentially expressed, then all genes in that operon are differentially expressed and (b) an analysis relatin
Transcriptional ontogeny of the developing liver
Janice S Lee, William O Ward, Geremy Knapp, Hongzu Ren, Beena Vallanat, Barbara Abbott, Karen Ho, Seth J Karp, J Corton
BMC Genomics , 2012, DOI: 10.1186/1471-2164-13-33
Abstract: We characterized gene expression changes in the developing mouse liver at gestational days (GD) 11.5, 12.5, 13.5, 14.5, 16.5, and 19 and in the neonate (postnatal day (PND) 7 and 32) compared to that in the adult liver (PND67) using full-genome microarrays. The fetal liver, and to a lesser extent the neonatal liver, exhibited dramatic differences in gene expression compared to adults. Canonical pathway analysis of the fetal liver signature demonstrated increases in functions important in cell replication and DNA fidelity whereas most metabolic pathways of intermediary metabolism were under expressed. Comparison of the dataset to a number of previously published microarray datasets revealed 1) a striking similarity between the fetal liver and that of the pancreas in both mice and humans, 2) a nucleated erythrocyte signature in the fetus and 3) under expression of most xenobiotic metabolism genes throughout development, with the exception of a number of transporters associated with either hematopoietic cells or cell proliferation in hepatocytes.Overall, these findings reveal the complexity of gene expression changes during liver development and maturation, and provide a foundation to predict responses to chemical and drug exposure as a function of early life-stages.The liver is the largest internal organ and provides many essential metabolic, exocrine and endocrine functions. The use of animal models including the mouse and primary cell cultures has identified many of the genes and pathways regulating embryonic liver development. These studies show that much of hepatogenesis is conserved throughout evolution. The liver, as well as the pancreas, develops from two unique spatial domains of the definitive endodermal epithelium of the embryonic foregut. Fate-mapping experiments have shown that the liver arises from lateral domains of endoderm in the developing ventral foregut as well as from endodermal cells that track along the ventral midline [1,2]. During closure of th
Kidney Toxicogenomics of Chronic Potassium Bromate Exposure in F344 Male Rats
David R. Geter, William O. Ward, Geremy W. Knapp, Anthony B. DeAngelo, Jessica A. Rubis, Russell D. Owen, James W. Allen and Don A. Delker
Translational Oncogenomics , 2012,
Abstract: Background: Potassium bromate (KBrO3), used in both the food and cosmetics industry, and a drinking water disinfection by-product, is a nephrotoxic compound and rodent carcinogen. To gain insight into the carcinogenic mechanism of action and provide possible biomarkers of KBrO3 exposure, the gene expression in kidneys from chronically exposed male F344 rats was investigated. Methods: Male F344 rats were exposed to KBrO3 in drinking water for 52 and 100 wk. Kidneys were removed, frozen, and stored at –80oC, then used for Affymetrix microarray analysis. Gene expression patterns were examined using a non-carcinogenic (20 ppm) and carcinogenic dose (400 ppm) at 52 wk, and compared to 100 wk high dose (400 ppm) and adenoma gene expression. Results: Statistical analysis revealed 144, 224, 43, and 994 genes out of 15866 from the 52 wk low, 52 wk high, 100 wk high, and adenomas respectively, were differentially expressed when compared to control kidneys. Gene ontology classification of the 52 wk high dose showed alterations of gene transcripts involved in oxidative stress, lipid metabolism, kidney function/ion transport, and cellular function. In a comparison of kidney development gene expression, alterations were seen in the adenomas but not in the 52 wk bromate-treated kidneys. However, the normal kidney from the high dose group resembled the adenoma expression pattern with early kidney development genes being up-regulated and adult phase genes being down-regulated. Moreover, eight genes were identified which could serve as biomarkers of carcinogenic exposure to bromate. The most promising of these was Pendrin, or Slc26a4, a solute carrier of chloride and iodide active in the kidney, thyroid, and inner ear. All these tissues are targets of KBrO3 toxicity. Expression array results were verified with quantitative real-time rtPCR. Conclusions: These data demonstrate that the 400 ppm carcinogenic dose of KBrO3 showed marked gene expression differences from the 20 ppm non-carcinogenic dose. Comparison of kidney development gene expression showed that the adenoma patterns were more characteristic of embryonic than adult kidneys, and that the normal kidney from the high dose group resembled the adenoma-like gene expression pattern. Taken together, the analysis from this study identifies potential biomarkers of exposure and illuminates a possible carcinogenic mode of action for KBrO3.
Better Global Polynomial Approximation for Image Rectification
Christopher O. Ward
Computer Science , 2009, DOI: 10.2316/Journal.205.2008.3.205-4669
Abstract: When using images to locate objects, there is the problem of correcting for distortion and misalignment in the images. An elegant way of solving this problem is to generate an error correcting function that maps points in an image to their corrected locations. We generate such a function by fitting a polynomial to a set of sample points. The objective is to identify a polynomial that passes "sufficiently close" to these points with "good" approximation of intermediate points. In the past, it has been difficult to achieve good global polynomial approximation using only sample points. We report on the development of a global polynomial approximation algorithm for solving this problem. Key Words: Polynomial approximation, interpolation, image rectification.
Mutation in Mouse Hei10, an E3 Ubiquitin Ligase, Disrupts Meiotic Crossing Over
Jeremy O Ward ,Laura G Reinholdt,William W Motley,Lisa M Niswander,Dekker C Deacon,Laurie B Griffin,Kristofor K Langlais,Vickie L Backus,Kerry J Schimenti,Marilyn J O'Brien,John J Eppig,John C Schimenti
PLOS Genetics , 2007, DOI: 10.1371/journal.pgen.0030139
Abstract: Crossing over during meiotic prophase I is required for sexual reproduction in mice and contributes to genome-wide genetic diversity. Here we report on the characterization of an N-ethyl-N-nitrosourea-induced, recessive allele called mei4, which causes sterility in both sexes owing to meiotic defects. In mutant spermatocytes, chromosomes fail to congress properly at the metaphase plate, leading to arrest and apoptosis before the first meiotic division. Mutant oocytes have a similar chromosomal phenotype but in vitro can undergo meiotic divisions and fertilization before arresting. During late meiotic prophase in mei4 mutant males, absence of cyclin dependent kinase 2 and mismatch repair protein association from chromosome cores is correlated with the premature separation of bivalents at diplonema owing to lack of chiasmata. We have identified the causative mutation, a transversion in the 5′ splice donor site of exon 1 in the mouse ortholog of Human Enhancer of Invasion 10 (Hei10; also known as Gm288 in mouse and CCNB1IP1 in human), a putative B-type cyclin E3 ubiquitin ligase. Importantly, orthologs of Hei10 are found exclusively in deuterostomes and not in more ancestral protostomes such as yeast, worms, or flies. The cloning and characterization of the mei4 allele of Hei10 demonstrates a novel link between cell cycle regulation and mismatch repair during prophase I.
Astronomical Sky Quality Near Eureka, in the Canadian High Arctic
Eric Steinbring,William Ward,James R. Drummond
Physics , 2011, DOI: 10.1086/664444
Abstract: Nighttime visible-light sky brightness and transparency are reported for the Polar Environment Research Laboratory (PEARL), located on a 610-m high ridge near the Eureka research station, on Ellesmere Island, Canada. Photometry of Polaris obtained in V band with the PEARL All Sky Imager (PASI) over two winters is supported by standard meteorological measurements and visual estimates of sky conditions from sea level. These data show that during the period of the study, October through March of 2008/09 and 2009/10, the sky near zenith had a mean surface brightness of 19.7 mag/square-arcsec when the sun was more than 12 deg below the horizon, reaching 20.7 mag/square-arcsec during astronomical darkness with no moon. Skies were without thick cloud and potentially usable for astronomy 86% of the time (extinction <2 mag). Up to 68% of the time was spectroscopic (<0.5 mag), attenuated by ice crystals, or clear with stable atmospheric transparency. Those conditions can persist for over 100 hours at a time. Further analysis suggests the sky was entirely free of ice crystals (truly photometric) 48+/-3% of the time at PEARL in winter, and that a higher elevation location nearby may be better.
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