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Search Results: 1 - 10 of 3981 matches for " Ryan Tewhey "
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Efficient and Cost Effective Population Resequencing by Pooling and In-Solution Hybridization
Vikas Bansal,Ryan Tewhey,Emily M. LeProust,Nicholas J. Schork
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0018353
Abstract: High-throughput sequencing of targeted genomic loci in large populations is an effective approach for evaluating the contribution of rare variants to disease risk. We evaluated the feasibility of using in-solution hybridization-based target capture on pooled DNA samples to enable cost-efficient population sequencing studies. For this, we performed pooled sequencing of 100 HapMap samples across ~600 kb of DNA sequence using the Illumina GAIIx. Using our accurate variant calling method for pooled sequence data, we were able to not only identify single nucleotide variants with a low false discovery rate (<1%) but also accurately detect short insertion/deletion variants. In addition, with sufficient coverage per individual in each pool (30-fold) we detected 97.2% of the total variants and 93.6% of variants below 5% in frequency. Finally, allele frequencies for single nucleotide variants (SNVs) estimated from the pooled data and the HapMap genotype data were tightly correlated (correlation coefficient > = 0.995).
Whole genome sequencing analysis of Plasmodium vivax using whole genome capture
A. Taylor Bright, Ryan Tewhey, Shira Abeles, Raul Chuquiyauri, Alejandro Llanos-Cuentas, Marcelo U Ferreira, Nicholas J Schork, Joseph M Vinetz, Elizabeth A Winzeler
BMC Genomics , 2012, DOI: 10.1186/1471-2164-13-262
Abstract: Here we show that in-solution hybridization capture can be used to extract P. vivax DNA from human contaminating DNA in the laboratory without the need for on-site leukocyte filtration. Using a whole genome capture method, we were able to enrich P. vivax DNA from bulk genomic DNA from less than 0.5% to a median of 55% (range 20%-80%). This level of enrichment allows for efficient analysis of the samples by whole genome sequencing and does not introduce any gross biases into the data. With this method, we obtained greater than 5X coverage across 93% of the P. vivax genome for four P. vivax strains from Iquitos, Peru, which is similar to our results using leukocyte filtration (greater than 5X coverage across 96% ).The whole genome capture technique will enable more efficient whole genome analysis of P. vivax from a larger geographic region and from valuable archived sample collections.
A High Resolution Case Study of a Patient with Recurrent Plasmodium vivax Infections Shows That Relapses Were Caused by Meiotic Siblings
Andrew Taylor Bright,Micah J. Manary,Ryan Tewhey,Eliana M. Arango,Tina Wang,Nicholas J. Schork,Stephanie K. Yanow ,Elizabeth A. Winzeler
PLOS Neglected Tropical Diseases , 2014, DOI: 10.1371/journal.pntd.0002882
Abstract: Plasmodium vivax infects a hundred million people annually and endangers 40% of the world's population. Unlike Plasmodium falciparum, P. vivax parasites can persist as a dormant stage in the liver, known as the hypnozoite, and these dormant forms can cause malaria relapses months or years after the initial mosquito bite. Here we analyze whole genome sequencing data from parasites in the blood of a patient who experienced consecutive P. vivax relapses over 33 months in a non-endemic country. By analyzing patterns of identity, read coverage, and the presence or absence of minor alleles in the initial polyclonal and subsequent monoclonal infections, we show that the parasites in the three infections are likely meiotic siblings. We infer that these siblings are descended from a single tetrad-like form that developed in the infecting mosquito midgut shortly after fertilization. In this natural cross we find the recombination rate for P. vivax to be 10 kb per centimorgan and we further observe areas of disequilibrium surrounding major drug resistance genes. Our data provide new strategies for studying multiclonal infections, which are common in all types of infectious diseases, and for distinguishing P. vivax relapses from reinfections in malaria endemic regions. This work provides a theoretical foundation for studies that aim to determine if new or existing drugs can provide a radical cure of P. vivax malaria.
Enrichment of sequencing targets from the human genome by solution hybridization
Ryan Tewhey, Masakazu Nakano, Xiaoyun Wang, Carlos Pabón-Pe?a, Barbara Novak, Angelica Giuffre, Eric Lin, Scott Happe, Doug N Roberts, Emily M LeProust, Eric J Topol, Olivier Harismendy, Kelly A Frazer
Genome Biology , 2009, DOI: 10.1186/gb-2009-10-10-r116
Abstract: Over the past several years, genome-wide association (GWA) studies have identified compelling statistical associations between more than 350 different loci in the human genome and common complex traits [1]. However, great difficulty occurs in moving beyond these statistical associations to identifying the causative variants and functional basis of the link between the genomic interval and the given complex trait. Population sequencing of these genomic intervals has been proposed as a method for identifying the causal common variants underlying the statistical associations and also for examining the potential contribution of rare variants in the interval to the complex trait of interest [1]. Next-generation sequencing technologies and their increased capacity have made it feasible to sequence efficiently hundreds of megabases of DNA. However, the current costs for sequencing entire human genomes makes this approach prohibitively expensive for population studies. Targeted sequencing of the specific loci associated with a complex trait in large numbers of individuals is a promising approach for using current sequencing technologies to identify and characterize the variants in these intervals. Additionally, population sequencing of candidate genes or the entire human exome may, in the near future, potentially make sequence-based association studies possible.Several methods have been proposed for enrichment of sequence targets from the human genome. PCR has been used to amplify a large hundred-kilobase-size interval associated with prostate cancer for targeted sequencing in 79 individuals [2] and also the exons of hundreds of genes to identify somatic mutations in hundreds of individual tumors [3,4]. Although PCR enriches target sequences with high specificity and sensitivity, it is difficult to scale the method. A second approach is hybridization-based methods using oligonucleotide probes either attached to a solid array [5-7] or in solution [8] to capture the sequencin
Genomic acquisition of a capsular polysaccharide virulence cluster by non-pathogenic Burkholderia isolates
Bernice Meng Qi Sim, Narisara Chantratita, Wen Fong Ooi, Tannistha Nandi, Ryan Tewhey, Vanaporn Wuthiekanun, Janjira Thaipadungpanit, Sarinna Tumapa, Pramila Ariyaratne, Wing-Kin Sung, Xiao Hui Sem, Hui Hoon Chua, Kalpana Ramnarayanan, Chi Ho Lin, Yichun Liu, Edward J Feil, Mindy B Glass, Gladys Tan, Sharon J Peacock, Patrick Tan
Genome Biology , 2010, DOI: 10.1186/gb-2010-11-8-r89
Abstract: Of 39 genomic regions variably present across the B. thailandensis strains, 13 regions corresponded to known genomic islands, while 26 regions were novel. Variant B. thailandensis isolates exhibited isolated acquisition of a capsular polysaccharide biosynthesis gene cluster (B. pseudomallei-like capsular polysaccharide) closely resembling a similar cluster in B. pseudomallei that is essential for virulence in mammals; presence of this cluster was confirmed by whole genome sequencing of a representative variant strain (B. thailandensis E555). Both whole-genome microarray and multi-locus sequence typing analysis revealed that the variant strains formed part of a phylogenetic subgroup distinct from the ancestral B. thailandensis population and were associated with atypical isolation sources when compared to the majority of previously described B. thailandensis strains. In functional assays, B. thailandensis E555 exhibited several B. pseudomallei-like phenotypes, including colony wrinkling, resistance to human complement binding, and intracellular macrophage survival. However, in murine infection assays, B. thailandensis E555 did not exhibit enhanced virulence relative to other B. thailandensis strains, suggesting that additional factors are required to successfully colonize and infect mammals.The discovery of such novel variant strains demonstrates how unbiased genomic surveys of non-pathogenic isolates can reveal insights into the development and emergence of new pathogenic species.The evolution of pathogen virulence is a complex process involving macrogenomic processes, such as large-scale gene acquisition and loss, combined with more subtle modifications of existing genes and regulatory pathways. Previous studies have shown that microbial pathogens can employ a variety of molecular factors to enable human and animal infection, such as type III toxin secretion systems, adhesins, and modulators of host signaling pathways [1-4]. As the compendium of virulence factors i
On the optimal stacking of noisy observations
?. Ryan
Mathematics , 2010,
Abstract: Observations where additive noise is present can for many models be grouped into a compound observation matrix, adhering to the same type of model. There are many ways the observations can be stacked, for instance vertically, horizontally, or quadratically. An estimator for the spectrum of the underlying model can be formulated for each stacking scenario in the case of Gaussian noise. We compare these spectrum estimators for the different stacking scenarios, and show that all kinds of stacking actually decreases the variance when compared to just taking an average of the observations. We show that, regardless of the number of observations, the variance of the estimator is smallest when the compound observation matrix is made as square as possible. When the number of observations grow, however, it is shown that the difference between the estimators is marginal: Two stacking scenarios where the number of columns and rows grow to infinity are shown to have the same variance asymptotically, even if the asymptotic matrix aspect ratios differ. Only the cases of vertical and horizontal stackings display different behaviour, giving a higher variance asymptotically. Models where not all kinds of stackings are possible are also discussed.
Site Specific Uncertainty in Regional Haze RuleHaze Indexes  [PDF]
Patrick A. Ryan
Atmospheric and Climate Sciences (ACS) , 2012, DOI: 10.4236/acs.2012.21001
Abstract: In 1999, the US Environmental Protection Agency (EPA) published the regional haze rule (RHR). The RHR default implementation plan calls for each class I area 20% worst baseline (2000-2004) visibility to improve linearly in time to natural conditions in 2064 and in calendar year 2018, each class I area 20% worst visibility is to comply with the 2018 visibility that falls on the linear improvement glide path from baseline (2000-2004) to natural (2064) conditions. This study shows that accurately assessing compliance depends on assessing the uncertainty in baseline, natural and 2018 visibility estimates. This study identifies ±3 dV and ±4 dV of uncertainty in 20% worst natural and baseline visibility estimates. The percent uncertainty in calculated 2018 glide path visibility values ranges from 10% - 45%.
Respiratory Sensitization & Sickness from Welding/Burning Isocyanate Containing Paints  [PDF]
Terrence Stobbe, Ryan Westra
Journal of Geoscience and Environment Protection (GEP) , 2014, DOI: 10.4236/gep.2014.24007
Abstract:

The purpose of this paper is to make the environmental and occupational health community aware of a serious health risk associated with the common practice of burning industrial paint off of metal surfaces during or prior to welding. On four occasions bystanders and welder/burner personnel have experienced illness as a result of being exposed to the combustion products of isocyanate paints that were being burned off metal surfaces. In each case, the burning and the exposed people were outside in an open environment where the health risk was thought to be minimal due to the open environment with nominal wind movement through the work area. In one case, the person (a burner) developed permanent sensitization to phthalic anhydride as a result of the exposure. Phthalic anhydride was determined to be decomposition product of burned isocyanate paint. In the other three cases (which involved very short exposures), between two and six people became ill but did not develop sensitization. Their symptoms included dizziness, nausea, headache, and breathing difficulty the severity of which varied from very uncomfortable to temporarily incapacitating. This paper discusses the circumstances associated with each event, the approach used to determine that phthalic anhydride was a decomposition product, and some practical things that can be done to avoid having employees become victims of exposure.

Support for obesity policy: The effect of perceptions of causes for obesity and national identity in Canada  [PDF]
Ryan Lange, Guy Faulkner
Open Journal of Preventive Medicine (OJPM) , 2012, DOI: 10.4236/ojpm.2012.24067
Abstract: Interventions in Canada to address obesity have largely been limited to individual-level change through education rather than a population-level public policy approach. Little is known about obesity policy support in Canada, and substantial national variation in obesity policy support prevents direct transferability of these policies among nations. Our study recruited 521 young adults for an online survey through leaflets and flyers. We investigated how respondents’ demographics, health characteristics, political attitudes, beliefs regarding causes of obesity, and national identity affected their support for obesity policy. Results showed that there is high support for many obesity policies among Canadian young adults. Including Canadian national identity in regression models was significant in explaining obesity policy support beyond the combined effect of other predictors. Further exploration of national identity, in Canada and elsewhere, has implications for understanding obesity policy support that might assist policy makers in making more informed decisions in addressing obesity.
A decomposition theorem for higher rank Coxeter groups
Ryan Blair,Ryan Ottman
Mathematics , 2010,
Abstract: In this paper, we show that any Coxeter graph which defines a higher rank Coxeter group must have disjoint induced subgraphs each of which defines a hyperbolic or higher rank Coxeter group. We then use this result to demonstrate several classes of Coxeter graphs which define hyperbolic Coxeter groups.
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