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  • 1
    In: Bioinformatics, Oxford University Press (OUP), Vol. 29, No. 22 ( 2013-11-15), p. 2877-2883
    Abstract: Motivation: Batch effects are due to probe-specific systematic variation between groups of samples (batches) resulting from experimental features that are not of biological interest. Principal component analysis (PCA) is commonly used as a visual tool to determine whether batch effects exist after applying a global normalization method. However, PCA yields linear combinations of the variables that contribute maximum variance and thus will not necessarily detect batch effects if they are not the largest source of variability in the data. Results: We present an extension of PCA to quantify the existence of batch effects, called guided PCA (gPCA). We describe a test statistic that uses gPCA to test whether a batch effect exists. We apply our proposed test statistic derived using gPCA to simulated data and to two copy number variation case studies: the first study consisted of 614 samples from a breast cancer family study using Illumina Human 660 bead-chip arrays, whereas the second case study consisted of 703 samples from a family blood pressure study that used Affymetrix SNP Array 6.0. We demonstrate that our statistic has good statistical properties and is able to identify significant batch effects in two copy number variation case studies. Conclusion: We developed a new statistic that uses gPCA to identify whether batch effects exist in high-throughput genomic data. Although our examples pertain to copy number data, gPCA is general and can be used on other data types as well. Availability and implementation: The gPCA R package (Available via CRAN) provides functionality and data to perform the methods in this article. Contact:  reesese@vcu.edu or eckel@mayo.edu Supplementary information:  Supplementary data are available at Bioinformatics online.
    Type of Medium: Online Resource
    ISSN: 1367-4811 , 1367-4803
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2013
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  • 2
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2023
    In:  Nicotine and Tobacco Research Vol. 25, No. 12 ( 2023-11-22), p. 1904-1908
    In: Nicotine and Tobacco Research, Oxford University Press (OUP), Vol. 25, No. 12 ( 2023-11-22), p. 1904-1908
    Abstract: Although the greater popularity of electronic cigarettes (EC) among asthmatics is alarming, there is limited knowledge of the long-term consequences of EC exposure in asthmatics. Aims and Methods Mild asthmatic C57/BL6J adult male and female mice were established by intranasal insufflation with three combined allergens. The asthmatic and age and sex-matched’ naïve mice were exposed to air, nicotine-free (propylene glycol [PG]/vegetable glycerin [VG] -only), or PG/VG+Nicotine, 4 hours daily for 3 months. The effects of EC exposure were accessed by measuring cytokines in bronchoalveolar lavage, periodic acid-schiff (PAS) staining, mitochondrial DNA copy numbers (mtCN), and the transcriptome in the lung. Significance was false discovery rate & lt;0.2 for transcriptome and 0.05 for the others. Results In asthmatic mice, PG/VG+Nicotine increased PAS-positive cells and IL-13 compared to mice exposed to air and PG/VG-only. In naïve mice exposed to PG/VG+Nicotine and PG/VG-only, higher INF-γ was observed compared to mice exposed only to air. PG/VG-only and PG/VG+Nicotine had significantly higher mtCN compared to air exposure in asthmatic mice, while the opposite pattern was observed in non-asthmatic naïve mice. Different gene expression patterns were profoundly found for asthmatic mice exposed to PG/VG+Nicotine compared to PG/VG-only, including genes involved in mitochondrial dysfunction, oxidative phosphorylation, and p21-activated kinase (PAK) signaling. Conclusions This study provides experimental evidence of the potential impact of nicotine enhancement on the long-term effects of EC in asthmatics compared to non-asthmatics. Implications The findings from this study indicate the potential impact of EC in asthmatics by addressing multiple biological markers. The long-term health outcomes of EC in the susceptible group can be instrumental in supporting policymaking and educational campaigns and informing the public, healthcare providers, and EC users about the underlying risks of EC use.
    Type of Medium: Online Resource
    ISSN: 1469-994X
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
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  • 3
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2016
    In:  Briefings in Bioinformatics
    In: Briefings in Bioinformatics, Oxford University Press (OUP)
    Type of Medium: Online Resource
    ISSN: 1467-5463 , 1477-4054
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2016
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  • 4
    In: Clinical Chemistry, Oxford University Press (OUP), Vol. 50, No. 11 ( 2004-11-01), p. 1994-2002
    Abstract: Background: Development of quality-control criteria to ensure reproducibility of microarray results for potential clinical application is still in its infancy. Methods: In the present studies we developed quality-control criteria and evaluated their effect in microarray data analysis using total RNA from cell lines, frozen tumors, and a commercially available reference RNA. Quality-control criteria such as A260/A280 ratios, percentage of rRNA, and median size of cDNA and cRNA synthesis products were evaluated for robustness in microarray analysis. Furthermore, precision studies using a reference material were performed on the Affymetrix® HG-U133A high-density oligonucleotide microarrays. The same reference RNA sample was examined in 16 different chips run on 2 different days in the four different modules of the Affymetrix fluidics workstation. Fresh and frozen fragmented cRNAs were also compared. An ANOVA model was fit to identify the main sources of variation. Results: Good-quality samples showed & gt;30% rRNA in the electropherograms and cDNA and cRNA synthesis products with median sizes of 2.0 and 3.0 kb, respectively. Precision studies showed that the main source of variation was the day-to-day variability, minimally affecting hybridization exogenous control genes. Altogether, the results showed that the Affymetrix Genechip® system is highly reproducible when RNA that meet the quality-control criteria are used (overall P & gt;0.01). Conclusions: These results confirm the need to establish defined quality-control criteria for sample quality to distinguish between analytical and biological variability.
    Type of Medium: Online Resource
    ISSN: 0009-9147 , 1530-8561
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2004
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  • 5
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2021
    In:  Briefings in Bioinformatics Vol. 22, No. 1 ( 2021-01-18), p. 334-345
    In: Briefings in Bioinformatics, Oxford University Press (OUP), Vol. 22, No. 1 ( 2021-01-18), p. 334-345
    Abstract: Many high-throughput genomic applications involve a large set of potential covariates and a response which is frequently measured on an ordinal scale, and it is crucial to identify which variables are truly associated with the response. Effectively controlling the false discovery rate (FDR) without sacrificing power has been a major challenge in variable selection research. This study reviews two existing variable selection frameworks, model-X knockoffs and a modified version of reference distribution variable selection (RDVS), both of which utilize artificial variables as benchmarks for decision making. Model-X knockoffs constructs a ‘knockoff’ variable for each covariate to mimic the covariance structure, while RDVS generates only one null variable and forms a reference distribution by performing multiple runs of model fitting. Herein, we describe how different importance measures for ordinal responses can be constructed that fit into these two selection frameworks, using either penalized regression or machine learning techniques. We compared these measures in terms of the FDR and power using simulated data. Moreover, we applied these two frameworks to high-throughput methylation data for identifying features associated with the progression from normal liver tissue to hepatocellular carcinoma to further compare and contrast their performances.
    Type of Medium: Online Resource
    ISSN: 1467-5463 , 1477-4054
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
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  • 6
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2006
    In:  Bioinformatics Vol. 22, No. 21 ( 2006-11-01), p. 2699-2701
    In: Bioinformatics, Oxford University Press (OUP), Vol. 22, No. 21 ( 2006-11-01), p. 2699-2701
    Abstract: Summary: This paper describes a stand-alone application for estimating the 3′ to 5′ ratio by fitting a mixed effects model to the interior pixel intensities of perfect match probes for selected control probe sets from an Affymetrix *.DAT file. The effectiveness of this method was demonstrated previously by an application of the method to two microarray datasets for which external verification of RNA quality was known. This application provides a more objective assessment of sample quality in that both a point estimate and 95% confidence interval about the 3′ to 5′ ratio are provided. Availability: The software and installation instructions are freely available for download at Contact:  kjarcher@vcu.edu
    Type of Medium: Online Resource
    ISSN: 1367-4811 , 1367-4803
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2006
    detail.hit.zdb_id: 1468345-3
    detail.hit.zdb_id: 1422668-6
    SSG: 12
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  • 7
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2006
    In:  Bioinformatics Vol. 22, No. 10 ( 2006-05-15), p. 1272-1274
    In: Bioinformatics, Oxford University Press (OUP), Vol. 22, No. 10 ( 2006-05-15), p. 1272-1274
    Abstract: Summary:  SScore is an R package that facilitates the comparison of gene expression between Affymetrix GeneChips using the S-score algorithm. The S-score algorithm uses probe level data directly to assess differences in gene expression, without requiring a preliminary separate step of probe set expression summary estimation. Therefore, the algorithm avoids introduction of error associated with the expression summary estimation process and has been demonstrated to improve the accuracy of identifying differentially expressed genes. The S-score produces accurate results even when few or no replicates are available. Availability: The R package SScore is available from Bioconductor at Contact:  rkennedy@vcu.edu
    Type of Medium: Online Resource
    ISSN: 1367-4811 , 1367-4803
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2006
    detail.hit.zdb_id: 1468345-3
    detail.hit.zdb_id: 1422668-6
    SSG: 12
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  • 8
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2022
    In:  Briefings in Bioinformatics Vol. 23, No. 6 ( 2022-11-19)
    In: Briefings in Bioinformatics, Oxford University Press (OUP), Vol. 23, No. 6 ( 2022-11-19)
    Abstract: For many high-dimensional genomic and epigenomic datasets, the outcome of interest is ordinal. While these ordinal outcomes are often thought of as the observed cutpoints of some latent continuous variable, some ordinal outcomes are truly discrete and are comprised of the subjective combination of several factors. The nonlinear stereotype logistic model, which does not assume proportional odds, was developed for these ‘assessed’ ordinal variables. It has previously been extended to the frequentist high-dimensional feature selection setting, but the Bayesian framework provides some distinct advantages in terms of simultaneous uncertainty quantification and variable selection. Here, we review the stereotype model and Bayesian variable selection methods and demonstrate how to combine them to select genomic features associated with discrete ordinal outcomes. We compared the Bayesian and frequentist methods in terms of variable selection performance. We additionally applied the Bayesian stereotype method to an acute myeloid leukemia RNA-sequencing dataset to further demonstrate its variable selection abilities by identifying features associated with the European LeukemiaNet prognostic risk score.
    Type of Medium: Online Resource
    ISSN: 1467-5463 , 1477-4054
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
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    SSG: 12
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  • 9
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2012
    In:  Neuro-Oncology Vol. 14, No. suppl 1 ( 2012-06-01), p. i82-i105
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 14, No. suppl 1 ( 2012-06-01), p. i82-i105
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2012
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    detail.hit.zdb_id: 2094060-9
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  • 10
    In: British Journal of Surgery, Oxford University Press (OUP), Vol. 110, No. 7 ( 2023-06-12), p. 804-817
    Abstract: Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries.
    Type of Medium: Online Resource
    ISSN: 0007-1323 , 1365-2168
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
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    detail.hit.zdb_id: 2006309-X
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