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  • 1
    In: Bioinformatics, Oxford University Press (OUP), Vol. 26, No. 17 ( 2010-09-01), p. 2136-2144
    Abstract: Motivation: One of the main goals of high-throughput gene-expression studies in cancer research is to identify prognostic gene signatures, which have the potential to predict the clinical outcome. It is common practice to investigate these questions using classification methods. However, standard methods merely rely on gene-expression data and assume the genes to be independent. Including pathway knowledge a priori into the classification process has recently been indicated as a promising way to increase classification accuracy as well as the interpretability and reproducibility of prognostic gene signatures. Results: We propose a new method called Reweighted Recursive Feature Elimination. It is based on the hypothesis that a gene with a low fold-change should have an increased influence on the classifier if it is connected to differentially expressed genes. We used a modified version of Google's PageRank algorithm to alter the ranking criterion of the SVM-RFE algorithm. Evaluations of our method on an integrated breast cancer dataset comprising 788 samples showed an improvement of the area under the receiver operator characteristic curve as well as in the reproducibility and interpretability of selected genes. Availability: The R code of the proposed algorithm is given in Supplementary Material. Contact:  m.johannes@DKFZ-heidelberg.de; tim.beissbarth@ams.med.uni-goettingen.de 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: 2010
    detail.hit.zdb_id: 1468345-3
    SSG: 12
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  • 2
    In: Proteome Science, Springer Science and Business Media LLC, Vol. 8, No. 1 ( 2010-12)
    Abstract: Reverse phase protein arrays (RPPA) emerged as a useful experimental platform to analyze biological samples in a high-throughput format. Different signal detection methods have been described to generate a quantitative readout on RPPA including the use of fluorescently labeled antibodies. Increasing the sensitivity of RPPA approaches is important since many signaling proteins or posttranslational modifications are present at a low level. Results A new antibody-mediated signal amplification (AMSA) strategy relying on sequential incubation steps with fluorescently-labeled secondary antibodies reactive against each other is introduced here. The signal quantification is performed in the near-infrared range. The RPPA-based analysis of 14 endogenous proteins in seven different cell lines demonstrated a strong correlation (r = 0.89) between AMSA and standard NIR detection. Probing serial dilutions of human cancer cell lines with different primary antibodies demonstrated that the new amplification approach improved the limit of detection especially for low abundant target proteins. Conclusions Antibody-mediated signal amplification is a convenient and cost-effective approach for the robust and specific quantification of low abundant proteins on RPPAs. Contrasting other amplification approaches it allows target protein detection over a large linear range.
    Type of Medium: Online Resource
    ISSN: 1477-5956
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2010
    detail.hit.zdb_id: 2141087-2
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  • 3
    In: Bioinformatics, Oxford University Press (OUP), Vol. 28, No. 13 ( 2012-07-01), p. 1714-1720
    Abstract: Motivation: There have been many successful experimental and bioinformatics efforts to elucidate transcription factor (TF)-target networks in several organisms. For many organisms, these annotations are complemented by miRNA-target networks of good quality. Attempts that use these networks in combination with gene expression data to draw conclusions on TF or miRNA activity are, however, still relatively sparse. Results: In this study, we propose Bayesian inference of regulation of transcriptional activity (BIRTA) as a novel approach to infer both, TF and miRNA activities, from combined miRNA and mRNA expression data in a condition specific way. That means our model explains mRNA and miRNA expression for a specific experimental condition by the activities of certain miRNAs and TFs, hence allowing for differentiating between switches from active to inactive (negative switch) and inactive to active (positive switch) forms. Extensive simulations of our model reveal its good prediction performance in comparison to other approaches. Furthermore, the utility of BIRTA is demonstrated at the example of Escherichia coli data comparing aerobic and anaerobic growth conditions, and by human expression data from pancreas and ovarian cancer. Availability and implementation: The method is implemented in the R package birta, which is freely available for Bio-conductor ( & gt;=2.10) on http://www.bioconductor.org/packages/release/bioc/html/birta.html. Contact:  frohlich@bit.uni-bonn.de 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: 2012
    detail.hit.zdb_id: 1468345-3
    SSG: 12
    Library Location Call Number Volume/Issue/Year Availability
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