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Search Results: 1 - 10 of 222887 matches for " Alexandra C. Schrimpe-Rutledge "
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VESPA: software to facilitate genomic annotation of prokaryotic organisms through integration of proteomic and transcriptomic data
Elena S Peterson, Lee Ann McCue, Alexandra C Schrimpe-Rutledge, Jeffrey L Jensen, Hyunjoo Walker, Markus A Kobold, Samantha R Webb, Samuel H Payne, Charles Ansong, Joshua N Adkins, William R Cannon, Bobbie-Jo M Webb-Robertson
BMC Genomics , 2012, DOI: 10.1186/1471-2164-13-131
Abstract: VESPA is a desktop Java? application that integrates high-throughput proteomics data (peptide-centric) and transcriptomics (probe or RNA-Seq) data into a genomic context, all of which can be visualized at three levels of genomic resolution. Data is interrogated via searches linked to the genome visualizations to find regions with high likelihood of mis-annotation. Search results are linked to exports for further validation outside of VESPA or potential coding-regions can be analyzed concurrently with the software through interaction with BLAST. VESPA is demonstrated on two use cases (Yersinia pestis Pestoides F and Synechococcus sp. PCC 7002) to demonstrate the rapid manner in which mis-annotations can be found and explored in VESPA using either proteomics data alone, or in combination with transcriptomic data.VESPA is an interactive visual analytics tool that integrates high-throughput data into a genomic context to facilitate the discovery of structural mis-annotations in prokaryotic genomes. Data is evaluated via visual analysis across multiple levels of genomic resolution, linked searches and interaction with existing bioinformatics tools. We highlight the novel functionality of VESPA and core programming requirements for visualization of these large heterogeneous datasets for a client-side application. The software is freely available at https://www.biopilot.org/docs/Software/Vespa.php webcite.High throughput (HTP) molecular technologies are at the core of new capabilities to derive genomic-level profiles oforganisms [1,2]. One challenge often not addressed in the context of HTP technologies is the relationship of the analyses to the defined structural annotation of the genome. For example, the accuracy of global bottom-up proteomics is directly dependent upon accurately defined open reading frames (ORFs), because spectra are matched directly to an in silico enzymatic digest of the predicted proteins. Although a well-annotated genome is typically needed to anal
The Genome Organization of Thermotoga maritima Reflects Its Lifestyle
Haythem Latif equal contributor,Joshua A. Lerman equal contributor,Vasiliy A. Portnoy,Yekaterina Tarasova,Harish Nagarajan,Alexandra C. Schrimpe-Rutledge,Richard D. Smith,Joshua N. Adkins,Dae-Hee Lee,Yu Qiu,Karsten Zengler
PLOS Genetics , 2013, DOI: 10.1371/journal.pgen.1003485
Abstract: The generation of genome-scale data is becoming more routine, yet the subsequent analysis of omics data remains a significant challenge. Here, an approach that integrates multiple omics datasets with bioinformatics tools was developed that produces a detailed annotation of several microbial genomic features. This methodology was used to characterize the genome of Thermotoga maritima—a phylogenetically deep-branching, hyperthermophilic bacterium. Experimental data were generated for whole-genome resequencing, transcription start site (TSS) determination, transcriptome profiling, and proteome profiling. These datasets, analyzed in combination with bioinformatics tools, served as a basis for the improvement of gene annotation, the elucidation of transcription units (TUs), the identification of putative non-coding RNAs (ncRNAs), and the determination of promoters and ribosome binding sites. This revealed many distinctive properties of the T. maritima genome organization relative to other bacteria. This genome has a high number of genes per TU (3.3), a paucity of putative ncRNAs (12), and few TUs with multiple TSSs (3.7%). Quantitative analysis of promoters and ribosome binding sites showed increased sequence conservation relative to other bacteria. The 5′UTRs follow an atypical bimodal length distribution comprised of “Short” 5′UTRs (11–17 nt) and “Common” 5′UTRs (26–32 nt). Transcriptional regulation is limited by a lack of intergenic space for the majority of TUs. Lastly, a high fraction of annotated genes are expressed independent of growth state and a linear correlation of mRNA/protein is observed (Pearson r = 0.63, p<2.2×10?16 t-test). These distinctive properties are hypothesized to be a reflection of this organism's hyperthermophilic lifestyle and could yield novel insights into the evolutionary trajectory of microbial life on earth.
Comparative Omics-Driven Genome Annotation Refinement: Application across Yersiniae
Alexandra C. Schrimpe-Rutledge, Marcus B. Jones, Sadhana Chauhan, Samuel O. Purvine, James A. Sanford, Matthew E. Monroe, Heather M. Brewer, Samuel H. Payne, Charles Ansong, Bryan C. Frank, Richard D. Smith, Scott N. Peterson, Vladimir L. Motin, Joshua N. Adkins
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0033903
Abstract: Genome sequencing continues to be a rapidly evolving technology, yet most downstream aspects of genome annotation pipelines remain relatively stable or are even being abandoned. The annotation process is now performed almost exclusively in an automated fashion to balance the large number of sequences generated. One possible way of reducing errors inherent to automated computational annotations is to apply data from omics measurements (i.e. transcriptional and proteomic) to the un-annotated genome with a proteogenomic-based approach. Here, the concept of annotation refinement has been extended to include a comparative assessment of genomes across closely related species. Transcriptomic and proteomic data derived from highly similar pathogenic Yersiniae (Y. pestis CO92, Y. pestis Pestoides F, and Y. pseudotuberculosis PB1/+) was used to demonstrate a comprehensive comparative omic-based annotation methodology. Peptide and oligo measurements experimentally validated the expression of nearly 40% of each strain's predicted proteome and revealed the identification of 28 novel and 68 incorrect (i.e., observed frameshifts, extended start sites, and translated pseudogenes) protein-coding sequences within the three current genome annotations. Gene loss is presumed to play a major role in Y. pestis acquiring its niche as a virulent pathogen, thus the discovery of many translated pseudogenes, including the insertion-ablated argD, underscores a need for functional analyses to investigate hypotheses related to divergence. Refinements included the discovery of a seemingly essential ribosomal protein, several virulence-associated factors, a transcriptional regulator, and many hypothetical proteins that were missed during annotation.
Differential gene expression mediated by 15-hydroxyeicosatetraenoic acid in LPS-stimulated RAW 264.7 cells
Alexandra C Schrimpe, David W Wright
Malaria Journal , 2009, DOI: 10.1186/1475-2875-8-195
Abstract: LPS-stimulated RAW 264.7 macrophage-like cells were treated with 40 μM 15(S)-HETE for 24 h, and microarray analysis was used to identify global gene expression alterations. Fold changes were calculated relative to LPS-stimulated cells and those genes altered at least 1.8-fold (p value ≤ 0.025) were considered to be differentially expressed. Expression levels of a subset of genes were assessed by qRT-PCR and used to confirm the microarray results.Network analysis revealed that altered genes were primarily associated with "lipid metabolism" and "small molecule biochemistry". While several genes associated with PPAR-gamma receptor-mediated signaling were differentially expressed, a number of genes indicated the activation of secondary signaling cascades. Genes related to cytoadherence (cell-cell and cell-matrix), leukocyte extravasation, and inflammatory response were also differentially regulated by treatment, supporting a potential role for 15(S)-HETE in malaria pathogenesis.These results add insight and detail to 15-HETE's effects on gene expression in macrophage-like cells. Data indicate that while 15-HETE exerts biological activity and may participate in Hz-mediated immuno-modulation, the gene expression changes are modest relative to those altered by the lipid peroxidation product HNE.Although haem is a vital cofactor for a diverse set of proteins involved in respiration, oxygen transport, and drug detoxification, the accumulation of free haem has deleterious effects. Haem is capable of binding to lipid bilayers, catalyzing lipid peroxidation, inhibiting enzymatic activity, and lysing cells and parasites [1,2]. Many organisms utilize the haem oxygenase pathway to degrade free haem. Blood-feeding Plasmodium parasites, the source of malaria infection, lack such a pathway. Consequently, haem released during haemoglobin catabolism is sequestered as the insoluble crystalline "malaria pigment" (i.e., haemozoin [Hz]). As most of the haem is occluded within the crystal,
Clinically relevant safety issues associated with St. John's wort product labels
Kevin A Clauson, Marile L Santamarina, Jennifer C Rutledge
BMC Complementary and Alternative Medicine , 2008, DOI: 10.1186/1472-6882-8-42
Abstract: Eight clinically relevant safety issues were identified: drug interactions (SJW-HIV medications, SJW-immunosupressants, SJW-oral contraceptives, and SJW-warfarin), contraindications (bipolar disorder), therapeutic duplication (antidepressants), and general considerations (phototoxicity and advice to consult a healthcare professional (HCP)). A list of SJW products was identified to assess their labels. Percentages and totals were used to present findings.Of the seventy-four products evaluated, no product label provided information for all 8 evaluation criteria. Three products (4.1%) provided information on 7 of the 8 criteria. Four products provided no safety information whatsoever. Percentage of products with label information was: SJW-HIV (8.1%), SJW-immunosupressants (5.4%), SJW-OCPs (8.1%), SJW-warfarin (5.4%), bipolar (1.4%), antidepressants (23.0%), phototoxicity (51.4%), and consult HCP (87.8%). Other safety-related information on labels included warnings about pregnancy (74.3%), lactation (64.9%), discontinue if adverse reaction (23.0%), and not for use in patients under 18 years old (13.5%). The average number of a priori safety issues included on a product label was 1.91 (range 0–8) for 23.9% completeness.The vast majority of SJW products fail to adequately address clinically relevant safety issues on their labeling. A few products do provide an acceptable amount of information on clinically relevant safety issues which could enhance the quality of counseling by HCPs and health store clerks. HCPs and consumers may benefit if the FDA re-examined labeling requirements for dietary supplements.St. John's wort (Hypericum perforatum), used most commonly for depression, is one of the top selling and best researched herbs used in the USA [1-3]. It is also popular in Canada and many countries in Europe – including Germany, where it is used more frequently than selective serotonin reuptake inhibitors (SSRIs) [4,5]. In addition to St. John's wort's (SJW) primary use i
Characterization by Mercury Porosimetry of Nonwoven Fiber Media with Deformation
Gregory C. Rutledge,Joseph L. Lowery,Chia-Ling Pai
Journal of Engineered Fibers and Fabrics , 2009,
Abstract: The porosity and pore diameter distribution are important characteristics of nonwoven fiber media. With the advent of electrospinning, the production of mats of nonwoven fibrous materials with fiber diameters in the 0.1-10 μm range has become more prevalent. The large compliance of these mats makes them susceptible to mechanical deformation under the pressures attained in a typical mercury porosimetry experiment. We report a theoretical analysis of the liquid volume measured during liquid intrusion porosimetry in the presence of deformation of such mats by one of two modes: buckling of the pores or elastic compression of the mat. For electrospun mats of poly(ε-caprolactone) with average fiber diameters ranging from 2.49 to 18.0 μm, we find that buckling is the more relevant mode of deformation, and that it can alter significantly the determination of pore diameter distributions measured by mercury porosimetry.
A Computational Auditory Scene Analysis-Enhanced Beamforming Approach for Sound Source Separation
L. A. Drake,J. C. Rutledge,J. Zhang,A. Katsaggelos
EURASIP Journal on Advances in Signal Processing , 2009, DOI: 10.1155/2009/403681
Abstract: Hearing aid users have difficulty hearing target signals, such as speech, in the presence of competing signals or noise. Most solutions proposed to date enhance or extract target signals from background noise and interference based on either location attributes or source attributes. Location attributes typically involve arrival angles at a microphone array. Source attributes include characteristics that are specific to a signal, such as fundamental frequency, or statistical properties that differentiate signals. This paper describes a novel approach to sound source separation, called computational auditory scene analysis-enhanced beamforming (CASA-EB), that achieves increased separation performance by combining the complementary techniques of CASA (a source attribute technique) with beamforming (a location attribute technique), complementary in the sense that they use independent attributes for signal separation. CASA-EB performs sound source separation by temporally and spatially filtering a multichannel input signal, and then grouping the resulting signal components into separated signals, based on source and location attributes. Experimental results show increased signal-to-interference ratio with CASA-EB over beamforming or CASA alone.
Multiresolution analysis in statistical mechanics. I. Using wavelets to calculate thermodynamic properties
Ahmed E. Ismail,Gregory C. Rutledge,George Stephanopoulos
Physics , 2002, DOI: 10.1063/1.1543581
Abstract: The wavelet transform, a family of orthonormal bases, is introduced as a technique for performing multiresolution analysis in statistical mechanics. The wavelet transform is a hierarchical technique designed to separate data sets into sets representing local averages and local differences. Although one-to-one transformations of data sets are possible, the advantage of the wavelet transform is as an approximation scheme for the efficient calculation of thermodynamic and ensemble properties. Even under the most drastic of approximations, the resulting errors in the values obtained for average absolute magnetization, free energy, and heat capacity are on the order of 10%, with a corresponding computational efficiency gain of two orders of magnitude for a system such as a $4\times 4$ Ising lattice. In addition, the errors in the results tend toward zero in the neighborhood of fixed points, as determined by renormalization group theory.
Multiresolution analysis in statistical mechanics. II. The wavelet transform as a basis for Monte Carlo simulations on lattices
Ahmed E. Ismail,George Stephanopoulos,Gregory C. Rutledge
Physics , 2002, DOI: 10.1063/1.1543582
Abstract: In this paper, we extend our analysis of lattice systems using the wavelet transform to systems for which exact enumeration is impractical. For such systems, we illustrate a wavelet-accelerated Monte Carlo (WAMC) algorithm, which hierarchically coarse-grains a lattice model by computing the probability distribution for successively larger block spins. We demonstrate that although the method perturbs the system by changing its Hamiltonian and by allowing block spins to take on values not permitted for individual spins, the results obtained agree with the analytical results in the preceding paper, and ``converge'' to exact results obtained in the absence of coarse-graining. Additionally, we show that the decorrelation time for the WAMC is no worse than that of Metropolis Monte Carlo (MMC), and that scaling laws can be constructed from data performed in several short simulations to estimate the results that would be obtained from the original simulation. Although the algorithm is not asymptotically faster than traditional MMC, because of its hierarchical design, the new algorithm executes several orders of magnitude faster than a full simulation of the original problem. Consequently, the new method allows for rapid analysis of a phase diagram, allowing computational time to be focused on regions near phase transitions.
Shoulda’ Put a Ring on It: Investigating Adult Attachment, Relationship Status, Anxiety, Mindfulness, and Resilience in Romantic Relationships  [PDF]
Aileen M. Pidgeon, Alexandra C. Giufre
Open Journal of Social Sciences (JSS) , 2014, DOI: 10.4236/jss.2014.211005
Abstract:

This study aimed to investigate the predictive ability of relationship status, anxiety, mindfulness, and resilience in relation to the two orthogonal dimensions of adult attachment: attachment anxiety and attachment avoidance. 156 participants completed measures assessing relationship status, adult attachment, anxiety, mindfulness and resilience. The results showed that resilience and the relationship status of single significantly predicted attachment anxiety, whereas anxiety and being either single or divorced significantly predicted attachment avoidance. A significant mediating role of resilience in the prediction of attachment anxiety from being single was also observed. The main implications of this study provided preliminary support for the significant predictive value of resilience in attachment anxiety.

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