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      A unified approach to false discovery rate estimation

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      1 ,
      BMC Bioinformatics
      BioMed Central

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          Abstract

          Background

          False discovery rate (FDR) methods play an important role in analyzing high-dimensional data. There are two types of FDR, tail area-based FDR and local FDR, as well as numerous statistical algorithms for estimating or controlling FDR. These differ in terms of underlying test statistics and procedures employed for statistical learning.

          Results

          A unifying algorithm for simultaneous estimation of both local FDR and tail area-based FDR is presented that can be applied to a diverse range of test statistics, including p-values, correlations, z- and t-scores. This approach is semipararametric and is based on a modified Grenander density estimator. For test statistics other than p-values it allows for empirical null modeling, so that dependencies among tests can be taken into account. The inference of the underlying model employs truncated maximum-likelihood estimation, with the cut-off point chosen according to the false non-discovery rate.

          Conclusion

          The proposed procedure generalizes a number of more specialized algorithms and thus offers a common framework for FDR estimation consistent across test statistics and types of FDR. In comparative study the unified approach performs on par with the best competing yet more specialized alternatives. The algorithm is implemented in R in the "fdrtool" package, available under the GNU GPL from http://strimmerlab.org/software/fdrtool/ and from the R package archive CRAN.

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          Most cited references23

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          Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing

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            Empirical Bayes Analysis of a Microarray Experiment

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              Estimating the occurrence of false positives and false negatives in microarray studies by approximating and partitioning the empirical distribution of p-values.

              The occurrence of false positives and false negatives in a microarray analysis could be easily estimated if the distribution of p-values were approximated and then expressed as a mixture of null and alternative densities. Essentially any distribution of p-values can be expressed as such a mixture by extracting a uniform density from it. The occurrence of false positives and false negatives in a microarray analysis could be easily estimated if the distribution of p-values were approximated and then expressed as a mixture of null and alternative densities. Essentially any distribution of p-values can be expressed as such a mixture by extracting a uniform density from it. An S-plus function library is available from http://www.stjuderesearch.org/statistics.
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                Author and article information

                Journal
                BMC Bioinformatics
                BMC Bioinformatics
                BioMed Central
                1471-2105
                2008
                9 July 2008
                : 9
                : 303
                Affiliations
                [1 ]Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Härtelstr. 16-18, 04107 Leipzig, Germany
                Article
                1471-2105-9-303
                10.1186/1471-2105-9-303
                2475539
                18613966
                7375e32c-73d0-4538-8cb1-a1cfc74b7aea
                Copyright © 2008 Strimmer; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 19 February 2008
                : 9 July 2008
                Categories
                Methodology Article

                Bioinformatics & Computational biology
                Bioinformatics & Computational biology

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