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    Bioinformatics. 2009 Oct 14. [Epub ahead of print]

    Integrated Analysis of Copy Number Alterations and Gene Expression: A Bivariate Assessment of Equally Directed Abnormalities.

    Schäfer M, Schwender H, Merk S, Haferlach C, Ickstadt K, Dugas M.

    Collaborative Research Center 475, TU Dortmund University, Dortmund, Germany, Department of Statistics, TU Dortmund University, Dortmund, Germany, Department of Biostatistics, Johns Hopkins University, Baltimore, USA, Galenus-G.H. AG, Basel, Switzerland, MLL Munich Leukemia Laboratory, Munich, Germany, Department of Medical Informatics and Biomathematics, University of Münster, Münster, Germany.

    MOTIVATION: The analysis of a number of different genetic features like copy number variation, gene expression or loss of heterocygosity has considerably increased in recent years, as well as the number of available data sets. This is particularly due to the success of microarray technology. Thus, to understand mechanisms of disease pathogenesis on a molecular basis, e.g., in cancer research, the challenge of analyzing such different data types in an integrated way has become increasingly important. In order to tackle this problem, we propose a new procedure for an integrated analysis of two different data types that searches for genes and genetic regions which for both inputs display strong equally directed deviations from the reference median. We employ this approach, based on a modified correlation coefficient and an explorative Wilcoxon test, to find DNA regions of such abnormalities in gene expression and copy number (e.g., underexpressed genes accompanied by a loss of DNA material). RESULTS: In an application to acute myeloid leukemia, our procedure is able to identify various regions on different chromosomes with characteristic abnormalities in gene expression and copy number data and shows a higher sensitivity to differences in abnormalities than standard approaches. While the results support various findings of previous studies, some new interesting DNA regions can be identified. In a simulation study, our procedure also shows more reliable results than standard approaches. AVAILABILITY: Code and data available as R packages edira and ediraAMLdata from http://www.statistik.tu-dortmund.de/~schaefer/ CONTACT: martin.schaefer@udo.edu SUPPLEMENTARY INFORMATION: Supplementary material is available at Bioinformatics online.

    PMID: 19828576 [PubMed - as supplied by publisher]

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