Title: Creating gene set activity profiles with time-series expression data

Authors: T.A. Knijnenburg, L.F.A. Wessels, M.J.T. Reinders

Addresses: Faculty of Electrical Engineering, Mathematics and Computer Science, Information and Communication Theory Group, Department of Mediamatics, Delft University of Technology, Mekelweg 4, 2628 CD Delft, The Netherlands. ' Department of Molecular Biology, Bioinformatics and Statistics, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. ' Faculty of Electrical Engineering, Mathematics and Computer Science, Information and Communication Theory Group, Department of Mediamatics, Delft University of Technology, Mekelweg 4, 2628 CD Delft, The Netherlands

Abstract: The use of predefined gene sets has become crucial in the interpretation of genomewide expression data. A limitation of the existing techniques that relate gene expression levels to gene sets is that they cannot readily be applied to time-course microarray data. The ability to attach statistical significance to the behaviour of biological processes over time would greatly contribute to understanding the complex regulatory mechanisms in the cell. We propose a statistical testing procedure based on the central limit theorem to assess the enrichment of a gene set. The technique is applied on time-course microarray data to generate gene-set specific |activity profiles|.

Keywords: time-series expression; gene expression data; gene sets; statistical testing; central limit theorem; CLT; activity profiles; bioinformatics; microarray.

DOI: 10.1504/IJBRA.2008.019577

International Journal of Bioinformatics Research and Applications, 2008 Vol.4 No.3, pp.306 - 323

Published online: 17 Jul 2008 *

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