Application of false discovery rate procedure to pairwise comparisons of refractive index of glass fragments

Pawluk-Kołc, M.; Ziȩba‐Palus, Janina; Parczewski, A.

doi:10.1016/j.forsciint.2005.08.016

Cited by 20 publications

(16 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Lung microarray data were first analyzed for genes that could differentiate patients with SSc‐related ILD from healthy controls. The most informative genes were defined as those with a false discovery rate (FDR) of <0.05 () (13,732 genes in total). Genes were hierarchically clustered for both samples and genes using complete linkage and unsupervised clustering.…”

Section: Resultsmentioning

confidence: 99%

“…Genes with an FDR of <0.05 () (13,732 genes in total) were further analyzed using Pearson's correlation, comparing lung gene expression from the microarray data with the corresponding change in FibMax for each SSc patient with NSIP. We preselected genes with at least 2‐fold greater induction in SSc patients with NSIP than in healthy controls, both to focus the analysis on genes showing relatively large changes in expression and to minimize the chance of false‐positive or nonspecific results.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Association of Interferon‐ and Transforming Growth Factor β–Regulated Genes and Macrophage Activation With Systemic Sclerosis–Related Progressive Lung Fibrosis

Christmann

Sampaio-Barros

Stifano

et al. 2014

Arthritis & Rheumatology

191

143

View full text Add to dashboard Cite

Objective Systemic sclerosis (SSc)–related interstitial lung disease (ILD) is one of the leading causes of mortality. We undertook this study to analyze the gene expression of lung tissue in a prospective cohort of patients with SSc-related ILD and to compare it with that in control lungs and with 2 prospective clinical parameters in order to understand the molecular pathways implicated in progressive lung disease. Methods Lung tissue was obtained by open lung biopsy in 28 consecutive patients with SSc-related ILD and in 4 controls. High-resolution computed tomography (HRCT) and pulmonary function testing (PFT) were performed at baseline and 2–3 years after treatment based on lung histologic classification. Microarray analysis was performed, and the results were correlated with changes in the HRCT score (FibMax) and PFT values. Quantitative polymerase chain reaction (qPCR) and immunohistochemistry were used to confirm differential levels of messenger RNA and protein. Results Lung microarray data distinguished patients with SSc-related ILD from healthy controls. In the lungs of patients with SSc-related ILD who had nonspecific interstitial pneumonia (NSIP), expressed genes included macrophage markers, chemokines, collagen, and transforming growth factor β (TGFβ)– and interferon (IFN)–regulated genes. Expression of these genes correlated with progressive lung fibrosis defined by the change in FibMax. Immunohistochemistry confirmed increased markers of collagen (COL1A1), IFN (OAS1 and IFI44), and macrophages (CCL18 and CD163), and the positive correlation with the change in FibMax was confirmed by qPCR in a larger group of SSc patients with NSIP. Several genes correlated with both the change in FibMax (r > 0.4) and the change in % predicted forced vital capacity (r < −0.1), including IFN and macrophage markers, chemokines, and heat-shock proteins. Conclusion These results highlight major pathogenic pathways relevant to progressive pulmonary fibrosis in SSc-related ILD: macrophage emigration and activation, and up-regulated expression of TGFβ- and IFN-regulated genes.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Association of Interferon‐ and Transforming Growth Factor β–Regulated Genes and Macrophage Activation With Systemic Sclerosis–Related Progressive Lung Fibrosis

Christmann

Sampaio-Barros

Stifano

et al. 2014

Arthritis & Rheumatology

191

143

View full text Add to dashboard Cite

show abstract

“…QuasiTel uses a quasi-likelihood method based on Poisson distribution—commonly used for count data (41)—and applies a regression model to compare spectral count data. This statistical model was used to perform pair-wise comparisons between two treatment conditions (six replicates/condition), which generated a single combined inventory of protein identifications (comparison data set); the model also uses F-tests to compute p values and the FDR method to correct for multiple hypothesis comparisons of identified proteins (42). Thresholds were set for p values (≤0.20), total spectral counts (11), and spectral count log 2 rate ratios (fold changes ≥ 2) generated by this model and were used as criteria to filter comparison data sets.…”

Section: Methodsmentioning

confidence: 99%

Protein Expression Signatures for Inhibition of Epidermal Growth Factor Receptor-mediated Signaling

Myers¹,

Manning²,

Coffey³

et al. 2012

Molecular & Cellular Proteomics

View full text Add to dashboard Cite

Analysis of cellular signaling networks typically involves targeted measurements of phosphorylated protein intermediates. However, phosphoproteomic analyses usually require affinity enrichment of phosphopeptides and can be complicated by artifactual changes in phosphorylation caused by uncontrolled preanalytical variables, particularly in the analysis of tissue specimens. We asked whether changes in protein expression, which are more stable and easily analyzed, could reflect network stimulation and inhibition. We employed this approach to analyze stimulation and inhibition of the epidermal growth factor receptor (EGFR) by EGF and selective EGFR inhibitors. Shotgun analysis of proteomes from proliferating A431 cells, EGF-stimulated cells, and cells co-treated with the EGFR inhibitors cetuximab or gefitinib identified groups of differentially expressed proteins. Comparisons of these protein groups identified 13 proteins whose EGF-induced expression changes were reversed by both EGFR inhibitors. Targeted multiple reaction monitoring analysis verified differential expression of 12 of these proteins, which comprise a candidate EGFR inhibition signature. We then tested these 12 proteins by multiple reaction monitoring analysis in three other models: 1) a comparison of DiFi (EGFR inhibitor-sensitive) and HCT116 (EGFR-insensitive) cell lines, 2) in formalin-fixed, paraffin-embedded mouse xenograft DiFi and HCT116 tumors, and 3) in tissue biopsies from a patient with the gastric hyperproliferative disorder Ménétrier's disease who was treated with cetuximab. Of the proteins in the candidate signature, a core group, including c-Jun, Jagged-1, and Claudin 4, were decreased by EGFR inhibitors in all three models. Although the goal of these studies was not to validate a clinically useful EGFR inhibition signature, the results confirm the hypothesis that clinically used EGFR inhibitors generate characteristic protein expression changes. This work further outlines a prototypical approach to derive and test protein expression signatures for drug action on signaling networks.

show abstract

“…Genes were ranked by log fold change, and a nonparametric Wilcoxon rank sum test was used to determine whether the genes annotated to a given GO category (or given pathway) and which show more differential expression than would be expected by chance alone. P-values were adjusted using the BenjaminiHochberg false discovery rate (Pawluk-Kolc et al 2006). …”

Section: Microarray and Data Analysismentioning

confidence: 99%

A novel 6C assay uncovers Polycomb-mediated higher order chromatin conformations

Tiwari¹,

Cope²,

McGarvey³

et al. 2008

Genome Res.

117

View full text Add to dashboard Cite

We describe construction of a novel modification, "6C," of chromatin looping assays that allows specific proteins that may mediate long-range chromatin interactions to be defined. This approach combines the standard looping approaches previously defined with an immunoprecipitation step to investigate involvement of the specific protein.The efficacy of this approach is demonstrated by using a Polycomb group (PcG) protein, Enhancer of Zeste (EZH2), as an example of how our assay might be used. EZH2, as a protein of the PcG complex, PRC2, has an important role in the propagation of epigenetic memory through deposition of the repressive mark, histone H3, lysine 27, tri-methylation (H3K27me3). Using our new 6C assay, we show how EZH2 is a direct mediator of long-range intraand interchromosomal interactions that can regulate transcriptional down-regulation of multiple genes by facilitating physical proximities between distant chromatin regions, thus targeting sites within to PcG machinery.[Supplemental material is available online at www.genome.org.]The past few years have seen an exciting development in technologies to address long-range chromatin interactions in vivo (3C, 4C, 5C, 3C-chip, ACT, open-ended 3C to name a few) (Dekker et al. 2002;Dostie et al. 2006;Ling et al. 2006;Lomvardas et al. 2006;Simonis et al. 2006;Wurtele and Chartrand 2006;Zhao et al. 2006). These techniques have revolutionized our concepts about key aspects of transcriptional regulation. However, all of these methodologies, to date, investigate physical proximities between chromatin elements without specifically identifying the protein components that may bridge them. Separate assays must then be carried out in order to address the potential role of specific regulatory factor(s) in mediating such long-range chromatin interactions. Moreover, when it comes to knowing whether a specific protein has the property to mediate physical pairing between distant chromatin elements, there have not yet been tools to specifically monitor this question.In the present work, we combine multiple techniques to construct a novel 6C (combined 3C-ChIP-cloning) assay to address the question of long-range chromatin interactions mediated by specific proteins. To demonstrate how this methodology can work, we focus the assay on the protein Enhancer of Zeste (EZH2). This protein is a key member of the Polycomb protein complex (PcG) that regulates long-term gene silencing in multiple organisms. PcG proteins play crucial roles during early embryonic development (Sparmann and van Lohuizen 2006; Ringrose 2007) and are important for the self-renewal and pluripotency of embryonic stem cells (Bernstein et al. 2006;Sparmann and van Lohuizen 2006). Among the PcG proteins, EZH2 is particularly important since it contains the histone methyltransferase (HMTase) activity that catalyzes trimethylation of histone H3 at Lys 27 (H3-K27) (Cao et al. 2002;Cao and Zhang 2004). This mark is required for attracting key components of PcG-mediated gene repression, and this activity is shown to ...

show abstract

Application of false discovery rate procedure to pairwise comparisons of refractive index of glass fragments

Cited by 20 publications

References 5 publications

Association of Interferon‐ and Transforming Growth Factor β–Regulated Genes and Macrophage Activation With Systemic Sclerosis–Related Progressive Lung Fibrosis

Association of Interferon‐ and Transforming Growth Factor β–Regulated Genes and Macrophage Activation With Systemic Sclerosis–Related Progressive Lung Fibrosis

Protein Expression Signatures for Inhibition of Epidermal Growth Factor Receptor-mediated Signaling

A novel 6C assay uncovers Polycomb-mediated higher order chromatin conformations

Contact Info

Product

Resources

About