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  • 1
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2008
    In:  Bioinformatics Vol. 24, No. 1 ( 2008-01-01), p. 78-85
    In: Bioinformatics, Oxford University Press (OUP), Vol. 24, No. 1 ( 2008-01-01), p. 78-85
    Abstract: Motivation: Several authors have studied expression in gene sets with specific goals: overrepresentation of interesting genes in functional groups, predictive power for class membership and searches for groups where the constituent genes show coordinated changes in expression under the experimental conditions. The purpose of this article is to follow the third direction. One important aspect is that the gene sets under analysis are known a priori and are not determined from the experimental data at hand. Our goal is to provide a methodology that helps to identify the relevant structural constituents (phenotypical, experimental design, biological component) that determine gene expression in a group. Results: Gene-wise linear models are used to formalize the structural aspects of a study. The full model is contrasted with a reduced model that lacks the relevant design component. A comparison with respect to goodness of fit is made and quantified. An asymptotic test and a permutation test are derived to test the null hypothesis that the reduced model sufficiently explains the observed expression within the gene group of interest. Graphical tools are available to illustrate and interpret the results of the analysis. Examples demonstrate the wide range of application. Availability: The R-package GlobalAncova (http://www.bioconductor.org) offers data and functions as well as a vignette to guide the user through specific analysis steps. Contact:  hummel@ibe.med.uni-muenchen.de
    Type of Medium: Online Resource
    ISSN: 1367-4811 , 1367-4803
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2008
    detail.hit.zdb_id: 1468345-3
    SSG: 12
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  • 2
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2011
    In:  Bioinformatics Vol. 27, No. 9 ( 2011-05-01), p. 1316-1317
    In: Bioinformatics, Oxford University Press (OUP), Vol. 27, No. 9 ( 2011-05-01), p. 1316-1317
    Abstract: Summary:  TEQC is an R/Bioconductor package for quality assessment of target enrichment experiments. Quality measures comprise specificity and sensitivity of the capture, enrichment, per-target read coverage and its relation to hybridization probe characteristics, coverage uniformity and reproducibility, and read duplicate analysis. Several diagnostic plots allow visual inspection of the data quality. Availability and implementation:  TEQC is implemented in the R language (version & gt;2.12.0) and is available as a Bioconductor package for Linux, Windows and MacOS from www.bioconductor.org. Contact:  manuela.hummel@crg.es
    Type of Medium: Online Resource
    ISSN: 1367-4811 , 1367-4803
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2011
    detail.hit.zdb_id: 1468345-3
    SSG: 12
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  • 3
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2016
    In:  BMC Genomics Vol. 17, No. 1 ( 2016-12)
    In: BMC Genomics, Springer Science and Business Media LLC, Vol. 17, No. 1 ( 2016-12)
    Type of Medium: Online Resource
    ISSN: 1471-2164
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2016
    detail.hit.zdb_id: 2041499-7
    SSG: 12
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  • 4
    In: BMC Genomics, Springer Science and Business Media LLC, Vol. 12, No. 1 ( 2011-12)
    Abstract: Epidermal Growth Factor (EGF) is a key regulatory growth factor activating many processes relevant to normal development and disease, affecting cell proliferation and survival. Here we use a combined approach to study the EGF dependent transcriptome of HeLa cells by using multiple long oligonucleotide based microarray platforms (from Agilent, Operon, and Illumina) in combination with digital gene expression profiling (DGE) with the Illumina Genome Analyzer. Results By applying a procedure for cross-platform data meta-analysis based on RankProd and GlobalAncova tests, we establish a well validated gene set with transcript levels altered after EGF treatment. We use this robust gene list to build higher order networks of gene interaction by interconnecting associated networks, supporting and extending the important role of the EGF signaling pathway in cancer. In addition, we find an entirely new set of genes previously unrelated to the currently accepted EGF associated cellular functions. Conclusions We propose that the use of global genomic cross-validation derived from high content technologies (microarrays or deep sequencing) can be used to generate more reliable datasets. This approach should help to improve the confidence of downstream in silico functional inference analyses based on high content data.
    Type of Medium: Online Resource
    ISSN: 1471-2164
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2011
    detail.hit.zdb_id: 2041499-7
    SSG: 12
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  • 5
    Online Resource
    Online Resource
    SAGE Publications ; 2008
    In:  Bioinformatics and Biology Insights Vol. 2 ( 2008-01), p. BBI.S1018-
    In: Bioinformatics and Biology Insights, SAGE Publications, Vol. 2 ( 2008-01), p. BBI.S1018-
    Abstract: The development of expression-based gene signatures for predicting prognosis or class membership is a popular and challenging task. Besides their stringent validation, signatures need a functional interpretation and must be placed in a biological context. Popular tools such as Gene Set Enrichment have drawbacks because they are restricted to annotated genes and are unable to capture the information hidden in the signature's non-annotated genes. Methodology We propose concepts to relate a signature with functional gene sets like pathways or Gene Ontology categories. The connection between single signature genes and a specific pathway is explored by hierarchical variable selection and gene association networks. The risk score derived from an individual patient's signature is related to expression patterns of pathways and Gene Ontology categories. Global tests are useful for these tasks, and they adjust for other factors. GlobalAncova is used to explore the effect on gene expression in specific functional groups from the interaction of the score and selected mutations in the patient's genome. Results We apply the proposed methods to an expression data set and a corresponding gene signature for predicting survival in Acute Myeloid Leukemia (AML). The example demonstrates strong relations between the signature and cancer-related pathways. The signature-based risk score was found to be associated with development-related biological processes. Conclusions Many authors interpret the functional aspects of a gene signature by linking signature genes to pathways or relevant functional gene groups. The method of gene set enrichment is preferred to annotating signature genes to specific Gene Ontology categories. The strategies proposed in this paper go beyond the restriction of annotation and deepen the insights into the biological mechanisms reflected in the information given by a signature.
    Type of Medium: Online Resource
    ISSN: 1177-9322 , 1177-9322
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2008
    detail.hit.zdb_id: 2423808-9
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  • 6
    Online Resource
    Online Resource
    The Company of Biologists ; 2011
    In:  Journal of Experimental Biology Vol. 214, No. 21 ( 2011-11-01), p. 3596-3604
    In: Journal of Experimental Biology, The Company of Biologists, Vol. 214, No. 21 ( 2011-11-01), p. 3596-3604
    Abstract: In the auditory system of bushcrickets, sound can reach the receptors via two different paths: (i) by acting on the outside of the tympana situated on both sides of each foreleg or (ii) through the acoustic trachea that opens at a spiracle on the thorax. While the spiracle is considered to be the main point of sound entry for higher audio and ultrasonic frequencies, the role of the tympana is still unclear. The tympana border the air-filled acoustic trachea as well as the fluid-filled haemolymph channel containing the receptor organs. To understand their role during sound transduction, the sound-induced neuronal response of the hearing organ was recorded in combination with measurement of tympanal membrane motion using laser-Doppler vibrometry. For far-field stimulation, the frequency of the most sensitive hearing (∼16 kHz) matched the frequency of a pronounced maximum of tympanal membrane vibration. A second maximum of tympanum motion at lower frequencies (∼7 kHz) was correlated with an increased nerve activity at higher intensities ( & gt;70 dB sound pressure level, SPL). These correlations support the hypothesis of functional coupling between tympanum motion and nerve activity. When sound stimuli were applied locally, through either the tympanum or the spiracle, significant differences between tympanum motion and nerve activity were found. These discrepancies show that tympanum motion and neuronal response are not coupled directly and that there is no linear relationship with the applied SPL. Taken together, these data verify a functional, albeit indirect, coupling of tympanum motion and sensory cell activity for one of the pronounced vibration maxima, which appears to represent a resonance frequency of the tympanum.
    Type of Medium: Online Resource
    ISSN: 1477-9145 , 0022-0949
    Language: English
    Publisher: The Company of Biologists
    Publication Date: 2011
    detail.hit.zdb_id: 1482461-9
    SSG: 12
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  • 7
    In: BMC Genomics, Springer Science and Business Media LLC, Vol. 14, No. 1 ( 2013-12)
    Abstract: Epidermal Growth Factor (EGF) plays an important function in the regulation of cell growth, proliferation, and differentiation by binding to its receptor (EGFR) and providing cancer cells with increased survival responsiveness. Signal transduction carried out by EGF has been extensively studied at both transcriptional and post-transcriptional levels. Little is known about the involvement of microRNAs (miRNAs) in the EGF signaling pathway. miRNAs have emerged as major players in the complex networks of gene regulation, and cancer miRNA expression studies have evidenced a direct involvement of miRNAs in cancer progression. Results In this study, we have used an integrative high content analysis approach to identify the specific miRNAs implicated in EGF signaling in HeLa cells as potential mediators of cancer mediated functions. We have used microarray and deep-sequencing technologies in order to obtain a global view of the EGF miRNA transcriptome with a robust experimental cross-validation. By applying a procedure based on Rankprod tests, we have delimited a solid set of EGF-regulated miRNAs. After validating regulated miRNAs by reverse transcription quantitative PCR, we have derived protein networks and biological functions from the predicted targets of the regulated miRNAs to gain insight into the potential role of miRNAs in EGF-treated cells. In addition, we have analyzed sequence heterogeneity due to editing relative to the reference sequence (isomiRs) among regulated miRNAs. Conclusions We propose that the use of global genomic miRNA cross-validation derived from high throughput technologies can be used to generate more reliable datasets inferring more robust networks of co-regulated predicted miRNA target genes.
    Type of Medium: Online Resource
    ISSN: 1471-2164
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2013
    detail.hit.zdb_id: 2041499-7
    SSG: 12
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  • 8
    Online Resource
    Online Resource
    Society for Neuroscience ; 2016
    In:  The Journal of Neuroscience Vol. 36, No. 8 ( 2016-02-24), p. 2377-2382
    In: The Journal of Neuroscience, Society for Neuroscience, Vol. 36, No. 8 ( 2016-02-24), p. 2377-2382
    Abstract: Mechanoelectrical transduction of acoustic signals is the fundamental process for hearing in all ears across the animal kingdom. Here, we performed in vivo laser-vibrometric and electrophysiological measurements at the transduction site in an insect ear ( Mecopoda elongata ) to relate the biomechanical tonotopy along the hearing organ to the frequency tuning of the corresponding sensory cells. Our mechanical and electrophysiological map revealed a biomechanical filter process that considerably sharpens the neuronal response. We demonstrate that the channel gating, which acts on chordotonal stretch receptor neurons, is based on a mechanical directionality of the sound-induced motion. Further, anatomical studies of the transduction site support our finding of a stimulus-relevant tilt. In conclusion, we were able to show, in an insect ear, that directionality of channel gating considerably sharpens the neuronal frequency selectivity at the peripheral level and have identified a mechanism that enhances frequency discrimination in tonotopically organized ears. SIGNIFICANCE STATEMENT The evolutionarily conserved ability of sensory cells to sense sound-induced mechanical forces is a fundamental process that still need investigating. In ears, the transduction process of acoustic signals from sound to frequency-specific neuronal responses of sensory cells is based on the opening of mechanosensitive ion channels. Here, we investigated mechanotransduction in the katydid's hearing organ with in vivo measurements of the sound-induced mechanical stimulus and of the electrical responses of the sensory cell at the transduction site. By combining anatomical, biophysical, and neurophysiological data, we present for the first time evidence of a crucial frequency-filter mechanism integral to the channel gating process. This filter takes effect at the first step of the signal transduction chain and shapes behavior-relevant hearing information.
    Type of Medium: Online Resource
    ISSN: 0270-6474 , 1529-2401
    Language: English
    Publisher: Society for Neuroscience
    Publication Date: 2016
    detail.hit.zdb_id: 1475274-8
    SSG: 12
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  • 9
    Online Resource
    Online Resource
    Elsevier BV ; 2016
    In:  Current Biology Vol. 26, No. 23 ( 2016-12), p. R1222-R1223
    In: Current Biology, Elsevier BV, Vol. 26, No. 23 ( 2016-12), p. R1222-R1223
    Type of Medium: Online Resource
    ISSN: 0960-9822
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2016
    detail.hit.zdb_id: 2019214-9
    SSG: 12
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  • 10
    Online Resource
    Online Resource
    Wiley ; 2020
    In:  Biometrical Journal Vol. 62, No. 3 ( 2020-05), p. 610-626
    In: Biometrical Journal, Wiley, Vol. 62, No. 3 ( 2020-05), p. 610-626
    Abstract: When performing survival analysis in very high dimensions, it is often required to reduce the number of covariates using preliminary screening. During the last years, a large number of variable screening methods for the survival context have been developed. However, guidance is missing for choosing an appropriate method in practice. The aim of this work is to provide an overview of marginal variable screening methods for survival and develop recommendations for their use. For this purpose, a literature review is given, offering a comprehensive and structured introduction to the topic. In addition, a novel screening procedure based on distance correlation and martingale residuals is proposed, which is particularly useful in detecting nonmonotone associations. For evaluating the performance of the discussed approaches, a simulation study is conducted, comparing the true positive rates of competing variable screening methods in different settings. A real data example on mantle cell lymphoma is provided.
    Type of Medium: Online Resource
    ISSN: 0323-3847 , 1521-4036
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 131640-0
    detail.hit.zdb_id: 1479920-0
    SSG: 12
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